棉铃虫Ha caspase-1和Ha hsc70基因克隆及表达研究
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摘要
棉铃虫(Helicoverpa armigera)属于鳞翅目夜蛾科(Lepidoptera Noctuidae)，在世界各地广泛分布，危害棉花、谷物、玉米、土豆、大豆、高粱和烟叶等农作物达上百种，往往造成巨大的经济损失，是我国和世界农业的主要害虫之一。目前棉铃虫防治中使用的大多数化学农药对环境和人类健康有害，而对于转基因作物如Bt抗虫棉的安全性也存在争议。因此在理论研究的基础上，发展新型生物农药一直是害虫防治的研究热点。
细胞凋亡，又称程序性细胞死亡(programmed cell death，PCD)，系机体生长发育、细胞分化以及病理状态中细胞自主性死亡，以清除多余、受伤或有害细胞而维持机体动态平衡，是机体正常生长发育过程中所必需的。本文从棉铃虫中克隆了两个在细胞凋亡中发挥重要作用的基因，Ha caspase-1和Ha hsc70，对它们的基因及演绎蛋白的序列进行了分析，并对Ha caspase-1的表达模式、调控和功能进行了研究。
一．棉铃虫Ha caspase-1基因克隆与表达
Caspase(cysteinylaspartate specific proteinase)是一类具有天冬氨酸特异性的半胱氨酸蛋白酶，是细胞凋亡过程中关键的作用因子，还具有调节细胞生长、增殖和分化等非凋亡功能。Caspase家族蛋白在生物界广泛存在，进化上保守性较高，在细胞凋亡中的功能相似。参与细胞凋亡的caspase家族蛋白根据其N端结构域prodomain的序列和长度，可分为两类，具有长prodomain的caspase为initiator caspase，发挥传递凋亡信号及激活下游caspase的作用；而具有短prodomain的caspase为effector caspase，直接作用于细胞内的底物，是凋亡的执行者。
本文采用同源克隆策略，从棉铃虫变态期cDNA文库中克隆到一个caspase基因，命名为Ha caspase-1。Ha caspase-1基因的cDNA全长1350bp，含有一个885bp的完整的开放阅读框，编码294个氨基酸，该演绎蛋白的理论分子量为33.5kDa，等电点为5.65。对该蛋白的结构域及活性位点分析结果显示，有caspase-p20和caspase-p10两个结构域，即大、小亚基；另外，该蛋白具有caspase蛋白酶催化作用所需的特征性的氨基酸残基His和Cys，如高度保守的QACQG五肽中的半胱氨酸残基(C_(176))。Ha caspase-1与其它物种caspase氨基酸序列比对结果显示，Ha caspase-1的prodomain较短，与草地夜蛾(Spodoptera frugiperda)Sf caspase-1和果蝇(Drosophila melanogaster)drICE同源性很高，与人caspase-3的相同序列也有32％，表明Ha caspase-1是一个下游caspase，即effector caspase。
采用Northern blot和半定量RT-PCR，对Ha caspase-1基因mRNA在幼虫不同组织中的表达模式进行了研究。结果显示，仅在5龄取食和6龄游走期幼虫的血细胞中检测到一条约1300 bases的杂交带，而且，6龄游走期幼虫的杂交信号略高于5龄取食幼虫。在取食和游走期幼虫的其它组织，表皮、脂肪体和中肠中均未检测到杂交信号，表明Ha caspase-1或在血细胞中特异性表达，或在血细胞中的表达显著高于其它组织中。而半定量RT-PCR结果显示，在血细胞中，Ha caspase-1在6龄游走期幼虫中的表达明显高于5龄取食幼虫，也明显高于其它组织，与Northern blot结果相符。但是，在取食幼虫的脂肪体以及游走幼虫的脂肪体和中肠中，也发现Ha caspase-1有低水平表达，这可能是由于PCR方法比Northern blot敏感性高，或因为血细胞黏附或进入脂肪体和中肠的缘故。
采用Northern blot对Ha caspase-1 mRNA在棉铃虫不同发育阶段的表达进行了研究。结果显示，Ha caspase-1在胚胎期有明显表达，这与胚胎时期有活跃的细胞凋亡发生是一致的。而在1龄到3龄的取食及蜕皮期幼虫整体中无表达，可能由于Ha caspase-1在整虫中表达水平太低而未检测到。从4龄到蛹期不同发育阶段的血细胞中，Ha caspase-1的表达水平在4龄及5龄蜕皮期和变态期有两次上升，似乎与从幼虫最后一次蜕皮到蛹形成期间的两次蜕皮激素脉冲释放有关。
采用原位杂交技术对Ha caspase-1在血细胞中表达定位进行了研究。结果显示Ha caspase-1仅在浆血细胞(plasmatocytes)和粒细胞(granulocytes)表达，而在原血细胞(prohaemocytes)和珠血细胞(spherulocytes)中无表达，Ha caspase-1在这两种血细胞中的表达可能与其参与幼虫变态过程有关。
由于Northern blot结果发现Ha caspase-1表达在4龄及5龄蜕皮期及变态期幼虫血细胞中上升，推测Ha caspase-1可能受到蜕皮激素20E的调控。因此，采用Northern blot和半定量RT-PCR对Ha caspase-1与蜕皮激素的关系进行研究。结果显示，体内注射蜕皮激素竞争物RH-2485可以使血细胞中Ha caspase-1的表达上升；20E可以上调体外培养的血细胞中Ha caspase-1的表达，表明在发育过程中Ha caspase-1的表达与蜕皮激素的释放有关，而且可能受蜕皮激素上调。
Ha caspase-1作为一种effector caspase，应该在细胞凋亡发挥作用。用苜蓿银纹夜蛾核型多角体病毒(Autographa Californica multiple nucleocapsid polyhedrovirus，AcMNPV)诱导培养的表皮细胞使之发生凋亡，观察分析了凋亡细胞的形态、DNA降解和Ha caspase-1的表达。AcMNPV诱导后表皮细胞发生了染色质疑集、胞膜皱缩、出现空泡等形态学上的变化，并解体为凋亡小体，核DNA的琼脂糖凝胶电泳显示出特异性的梯形DNA图谱。Ha caspase-1 RT-PCR的结果显示，比之未诱导的细胞，凋亡细胞中Ha caspase-1表达明显上升，表明Ha caspase-1的确在细胞凋亡中发挥作用。
采用基因特异引物，PCR扩增得到含ORF的Ha caspase-1基因片断，并克隆到原核表达载体pET-30a(+)中，构建了重组表达质粒Ha casp/pET-30a(+)，并成功地在大肠杆菌BL21(DE3)菌株中进行了重组蛋白的表达，为研究Ha caspase-1的功能奠定了基础。
二．棉铃虫Ha hsc70基因克隆
热休克蛋白(heat shock proteins，Hsps)是一类高度保守的蛋白，具有极为广泛的生物学功能，不仅在应激反应中发挥重要作用，维持细胞自稳，保护细胞生命活动，而且参与细胞凋亡、免疫调控、肿瘤及病毒感染等生理、病理过程。Hsps是一个成员众多的蛋白超家族，其中Hsp70家族是Hsps中最保守和最重要的一族。
本文采用同源克隆策略，从棉铃虫变态幼虫表皮SMART cDNA中克隆了一个hsc70基因，命名为Ha hsc70。Ha hsc70基因的cDNA全长2145bp，具有一个长1965bp完整的开放阅读框，编码含654个氨基酸的Hsc70蛋白。该蛋白的理论分子量为71.6kDa，等电点为5.24。对Ha Hsc70蛋白的结构域分析结果显示，仅有一个大的HSP70结构域，无信号肽序列。比对Ha Hsc70与其它物种Hsc70的蛋白序列，结果显示Ha Hsc70与其它昆虫Hsc70的序列一致性高达90％以上，与高等哺乳动物及人Hsc70的序列一致性也达80％以上，与植物Hsc70、微生物Hsp70的序列一致性分别有70％及45％左右，说明Hsc70在进化上的确非常保守。
综上所述，本文首次克隆了棉铃虫的一个caspase基因，Ha caspase-1，序列分析及比对结果显示，Ha caspase-1是一个下游的effector caspase。Ha caspase-1在棉铃虫幼虫不同发育阶段的表达模式，及其在体内、体外均可被RH-2485和20E诱导上升表达的结果，提示Ha caspase-1可能受蜕皮激素上调，在棉铃虫的蜕皮及变态发育中发挥作用。Ha caspase-1在凋亡细胞中的高表达，证实了其effector caspase的功能。本文还首次克隆了棉铃虫的一个hsp基因，Ha hscT0，序列分析及比对结果显示，Ha hsc70与其它物种hsc70高度同源，对Ha hsc70的表达及功能等尚在研究之中。
细胞凋亡在生物体生长发育、细胞增殖与分化中发挥重要作用，Caspase是细胞凋亡途径中关键的作用因子，Hsps参与细胞凋亡调控，而且Caspase与Hsps之间存在相互作用。对棉铃虫Ha caspase-1和Ha hsc70基因性质、表达及功能进行研究，在此基础上研制安全性较高的抑制害虫生长发育的新型生物农药，对于发展棉铃虫防治的新方法及新途径具有重要意义。另一方面，通过对Ha caspase-1和Ha hsc70基因功能及其调控的研究，也可以进一步了解细胞凋亡发生发展的机制，从而阐明昆虫变态发育中的分子生物学机理。
The cotton bollworm, Helicoverpa armigera, which belongs to Lepidoptera Noctuidae, distributes broadly in the world and harms a lot of crops including cotton, cereal, corn, potato, bean and tobacco leaf. The cotton bollworm is one of the major pests of the world agriculture, which often brings great lost in economy. At the present time, the majority chemical pesticides used to prevent cotton bollworm are harmful to human and environment, and there is controversy on the security of the transgene crops such as the Bt cotton. Therefore, development of the biological pesticides based on the theory studies is always the focus of the pest prevention.
Apoptosis, or programmed cell death (PCD), a process of cell suicide, which eliminates superfluous, damaged or deleterious cells during development, cell differentiation, and disease to maintain homeostasis, is essential to the development of organisms. In this study, two genes, Ha caspase-1 and Ha hsc70, involved in apoptosis were cloned from H. armigera. Sequences of the genes and the deduced proteins were analyzed, and the expression pattern, induction expression and function of Ha caspase-1 were investigated. 1. Cloning and expression of Ha caspaase-1 from H. armigera
Caspase (cysteinylaspartate specific proteinase) is a group of cysteine proteinase with substrate specificity at aspartate, which is the key factor in apoptosis and has non-apoptotic functions in cell survival, proliferation and differentiation. The proteins of caspase family are evolutionally conserved, executing the similar function in apoptosis. The caspases involved in apoptosis are divided into two groups according to the sequences of their N terminal domain named prodomain. The caspases with long prodomain are the initiator caspases which transfer the signals of apoptosis and activate the downstream caspases, while the caspsaes with short prodomain are the effector caspases which cleavage the substrates in cell and are the direct executioners of apoptosis.
In this study, a caspase gene named Ha caspase-1 was cloned from the cDNA library of metamorphically committed H. armigera using the strategy of homologous cloning. The full-length of Ha caspase-1 cDNA is 1350 bp, including an 885 bp open reading frame (ORF) that encodes 294 amino acids. The deduced protein has a computed molecular mass of 33.5 kDa and a predicted isoelectric point of 5.65. Sequence analysis of the domain and active site shows that the protein has two domains, caspase-p20 and caspase-p10, which are the large subunit and the small subunit, respectively. In addition, the predicted protein contains the typical residues His and Cys required for catalysis by caspases and the catalytic cysteine (C_(176)) located in a QACQG pentapeptide is an example. Sequence alignment of amino acids of Ha caspase-1 with other known caspases revealed that it has a short prodomian and is great homologous to Sf caspase-1of Spodoptera frugiperda and drICE of Drosophila melanogaster. The homology of Ha caspase-1 to human caspase-3 is even 32%. These results suggested that Ha caspase-1 is an effector caspase in downstream of caspase cascade.
Northern blot analysis and semi-quantitative RT-PCR were used to investigate the expression pattern of Ha caspase-1 in different larval tissues. The result of Northern blot showed that the Ha caspase-1 mRNA was only detected in the feeding and wandering larval haemocytes, with the concentration in haemocytes of wandering larvae slightly higher than that in haemocytes of feeding ones. There was no positive signal detected in the epidermis, midgut, fat body from both feeding and wandering larvae, suggesting that either the expression of Ha caspase-1 mRNA was probably haemocyte-specific or its mRNA concentration in haemocytes was significantly higher than that of the other tissues. The result of RT-PCR showed that the signal detected in haemocytes from wandering larvae was much stronger than that in feeding ones and other tissues, in agreement with that of Northern blot. However, in the feeding larval fat body and the midgut and wandering larval fat body, Ha caspase-1 was also found at lower levels, which is different from the result of Northern blot and may be due to the higher sensitivity of PCR compared with Northern blot, or haemocytes attachment or migration into fat body and midgut.
Northern blot analysis was applied to determine the developmental profiles of Ha caspase-1 mRNA levels. The results revealed that Ha caspase-1 was expressed in embryos, which is consistent with the notion that cell death is extensive during embryogenesis, but there is no Ha caspase-1 detected in younger instar larvae (lst~3rd) by whole body preparation of mRNA, which may because Ha caspase-1 mRNA level is too low to be detected in these early developmental stages. However, in later instar larval haemocytes (4th—6th instar), Ha caspase-1 mRNA concentration was higher during 4th and 5th molting and wandering stages, which appears to be correlate with the two waves of ecdysone during the periods of last larva molting and metamoephosis.
In situ hybridization was performed to locate the transcript of Ha caspaes-1 in haemocytes. Results indicated that the plasmatocytes and granulocytes in haemocytes from 6th instar wandering larvae released extensive Ha caspase-1 signal. Other cells, including prohaemocytes and spherulocytes, did not show obvious signal compared with the negative control cells. The expression of Ha caspase-1 in these two kinds of haemocytes suggested that Ha caspase-1 may be involved in the larval-pupal metamorphosis because the populations of both plasmatocytes and granulocytes increased in the late stage of the last instar larvae.
Because Ha caspase-1 mRNA levels increased in haemocytes during molting and metamoephosis, it is inferred that Ha caspase-1 should be regulated by 20-hydroxyecdysone (20E). Therefore, the relationship between Ha caspase-1 and ecdysone was measured through Northern blot analysis and RT-PCR. Results showed that Ha caspase-1 expression increased in haemocytes in vivo after ecdysone agonist RH-2485 injection and Ha caspase-1 mRNA also went up in haemocytes in vitro after treated with 20E, suggesting that Ha caspase-1 expression during development correlates to the release of ecdysone.
As an effector caspase, Ha caspase-1 should play a role in apoptosis. The morphological alterations, DNA degeneration and Ha caspase-1 expression was therefore observed in the cultured epidermis cells undergoing apoptosis induced by AcMNPV (Autographa Californica multiple nucleocapsid polyhedrovirus). After AcMNPV induction, the morphological changes on cells including chromatin condensation, membrane shrinkage and vacuole appearance and apoptotic bodies were observed. In addition, nuclear DNA presented the DNA ladder on agarose gel electrophoresis. The result of RT-PCR showed that Ha caspase-1 expression in cells induced by AcMNPV was much higher than that in the non-induced cells, indicating that Ha caspase-1 is a function factor involvd in apopotosis.
In addition, a fragment containing ORF of Ha caspase-1 was subcloned into prokaryotic expression vector pET-30a(+) to construct recombined plasmid Ha casp/pET-30a(+), and recombinant protein was highly expressed in E. coli strain BL21(DE3), which are to be used for function study on Ha caspase-1.
2. Cloning of Ha hsc70 from H. armigera
Heat shock protein is a group of greatly conserved proteins, which has a broad range of biochemical functions. Hsps not only play indispensable roles in the stress reaction to maintain the self-stabilization of cell and avoid the damage of cell, but also participate in apoptosis, immune regulation, tumor and infection. Hsps is a super family including a large number of members in which Hsp70 family is the most conserved and important.
In this study, a hsc70 gene named Ha hsc70 was cloned from the SMART cDNA of epidermis from the metamorphically committedally committed H. armigera using the strategy of homologous cloning. The full-length Ha hsc70 cDNA is 2145 bp, including a 1965 bp ORF that encodes 654 amino acids. The deduced protein has a computed molecular mass of 71.6 kDa and a predicted isoelectric point of 5.24. Sequence analysis shows the protein has only one large HSP70 domain without signal peptide. Sequence alignment of amino acids of Ha Hsc70 with other known Hsc70 revealed it has the greatest homology to the Hsc70 of other insects, with an identity over 90%. The identity of Ha Hsc70 to mammal and human Hsc70s also reaches 80%. The identities of Ha Hsc70 to plant and prokaryotic Hsc70s (or Hsp70s) are even about 70% and 45%, implying that Hsc70 is greatly evolutionally conserved.
In summary, we cloned a caspase gene from H. armigera , Ha caspase-1, which is a effector caspase resulted from the sequence analysis and alignment. The expression profiles of Ha caspase-1 during development and induced expression of Ha caspase-1 by RH-2485 in vivo and 20E in vitro imply that Ha caspase-lmay be up regulated by ecdysone and play a role during molting and metamorphosis. The high expression of Ha caspase-1 in the apoptotic cells approves of its function as an effector caspase. We also cloned a hsp70 gene from H. armigera, Ha hsc70, which is highly homologous to hsc70 of other species resulted from the sequence analysis and alignment. The expression and function of Ha hsc70 is under study now.
Apoptosis plays an essential role in development, cell proliferation and differentiation. Caspases are the key regulator in the apoptotic pathways, Hsps also participate in apoptosis, and the interaction exists between caspases and Hsps. To develop biological pesticides with high security based on the study of the characterization, expression and function of both caspase and Hsps is important to the exploitation of new methods for pest control. On the other hand, to study the function and regulation of genes involved in apoptosis during insect development is in favor of better understanding the mechanism of apoptosis and insect development.
细胞凋亡，又称程序性细胞死亡(programmed cell death，PCD)，系机体生长发育、细胞分化以及病理状态中细胞自主性死亡，以清除多余、受伤或有害细胞而维持机体动态平衡，是机体正常生长发育过程中所必需的。本文从棉铃虫中克隆了两个在细胞凋亡中发挥重要作用的基因，Ha caspase-1和Ha hsc70，对它们的基因及演绎蛋白的序列进行了分析，并对Ha caspase-1的表达模式、调控和功能进行了研究。
一．棉铃虫Ha caspase-1基因克隆与表达
Caspase(cysteinylaspartate specific proteinase)是一类具有天冬氨酸特异性的半胱氨酸蛋白酶，是细胞凋亡过程中关键的作用因子，还具有调节细胞生长、增殖和分化等非凋亡功能。Caspase家族蛋白在生物界广泛存在，进化上保守性较高，在细胞凋亡中的功能相似。参与细胞凋亡的caspase家族蛋白根据其N端结构域prodomain的序列和长度，可分为两类，具有长prodomain的caspase为initiator caspase，发挥传递凋亡信号及激活下游caspase的作用；而具有短prodomain的caspase为effector caspase，直接作用于细胞内的底物，是凋亡的执行者。
本文采用同源克隆策略，从棉铃虫变态期cDNA文库中克隆到一个caspase基因，命名为Ha caspase-1。Ha caspase-1基因的cDNA全长1350bp，含有一个885bp的完整的开放阅读框，编码294个氨基酸，该演绎蛋白的理论分子量为33.5kDa，等电点为5.65。对该蛋白的结构域及活性位点分析结果显示，有caspase-p20和caspase-p10两个结构域，即大、小亚基；另外，该蛋白具有caspase蛋白酶催化作用所需的特征性的氨基酸残基His和Cys，如高度保守的QACQG五肽中的半胱氨酸残基(C_(176))。Ha caspase-1与其它物种caspase氨基酸序列比对结果显示，Ha caspase-1的prodomain较短，与草地夜蛾(Spodoptera frugiperda)Sf caspase-1和果蝇(Drosophila melanogaster)drICE同源性很高，与人caspase-3的相同序列也有32％，表明Ha caspase-1是一个下游caspase，即effector caspase。
采用Northern blot和半定量RT-PCR，对Ha caspase-1基因mRNA在幼虫不同组织中的表达模式进行了研究。结果显示，仅在5龄取食和6龄游走期幼虫的血细胞中检测到一条约1300 bases的杂交带，而且，6龄游走期幼虫的杂交信号略高于5龄取食幼虫。在取食和游走期幼虫的其它组织，表皮、脂肪体和中肠中均未检测到杂交信号，表明Ha caspase-1或在血细胞中特异性表达，或在血细胞中的表达显著高于其它组织中。而半定量RT-PCR结果显示，在血细胞中，Ha caspase-1在6龄游走期幼虫中的表达明显高于5龄取食幼虫，也明显高于其它组织，与Northern blot结果相符。但是，在取食幼虫的脂肪体以及游走幼虫的脂肪体和中肠中，也发现Ha caspase-1有低水平表达，这可能是由于PCR方法比Northern blot敏感性高，或因为血细胞黏附或进入脂肪体和中肠的缘故。
采用Northern blot对Ha caspase-1 mRNA在棉铃虫不同发育阶段的表达进行了研究。结果显示，Ha caspase-1在胚胎期有明显表达，这与胚胎时期有活跃的细胞凋亡发生是一致的。而在1龄到3龄的取食及蜕皮期幼虫整体中无表达，可能由于Ha caspase-1在整虫中表达水平太低而未检测到。从4龄到蛹期不同发育阶段的血细胞中，Ha caspase-1的表达水平在4龄及5龄蜕皮期和变态期有两次上升，似乎与从幼虫最后一次蜕皮到蛹形成期间的两次蜕皮激素脉冲释放有关。
采用原位杂交技术对Ha caspase-1在血细胞中表达定位进行了研究。结果显示Ha caspase-1仅在浆血细胞(plasmatocytes)和粒细胞(granulocytes)表达，而在原血细胞(prohaemocytes)和珠血细胞(spherulocytes)中无表达，Ha caspase-1在这两种血细胞中的表达可能与其参与幼虫变态过程有关。
由于Northern blot结果发现Ha caspase-1表达在4龄及5龄蜕皮期及变态期幼虫血细胞中上升，推测Ha caspase-1可能受到蜕皮激素20E的调控。因此，采用Northern blot和半定量RT-PCR对Ha caspase-1与蜕皮激素的关系进行研究。结果显示，体内注射蜕皮激素竞争物RH-2485可以使血细胞中Ha caspase-1的表达上升；20E可以上调体外培养的血细胞中Ha caspase-1的表达，表明在发育过程中Ha caspase-1的表达与蜕皮激素的释放有关，而且可能受蜕皮激素上调。
Ha caspase-1作为一种effector caspase，应该在细胞凋亡发挥作用。用苜蓿银纹夜蛾核型多角体病毒(Autographa Californica multiple nucleocapsid polyhedrovirus，AcMNPV)诱导培养的表皮细胞使之发生凋亡，观察分析了凋亡细胞的形态、DNA降解和Ha caspase-1的表达。AcMNPV诱导后表皮细胞发生了染色质疑集、胞膜皱缩、出现空泡等形态学上的变化，并解体为凋亡小体，核DNA的琼脂糖凝胶电泳显示出特异性的梯形DNA图谱。Ha caspase-1 RT-PCR的结果显示，比之未诱导的细胞，凋亡细胞中Ha caspase-1表达明显上升，表明Ha caspase-1的确在细胞凋亡中发挥作用。
采用基因特异引物，PCR扩增得到含ORF的Ha caspase-1基因片断，并克隆到原核表达载体pET-30a(+)中，构建了重组表达质粒Ha casp/pET-30a(+)，并成功地在大肠杆菌BL21(DE3)菌株中进行了重组蛋白的表达，为研究Ha caspase-1的功能奠定了基础。
二．棉铃虫Ha hsc70基因克隆
热休克蛋白(heat shock proteins，Hsps)是一类高度保守的蛋白，具有极为广泛的生物学功能，不仅在应激反应中发挥重要作用，维持细胞自稳，保护细胞生命活动，而且参与细胞凋亡、免疫调控、肿瘤及病毒感染等生理、病理过程。Hsps是一个成员众多的蛋白超家族，其中Hsp70家族是Hsps中最保守和最重要的一族。
本文采用同源克隆策略，从棉铃虫变态幼虫表皮SMART cDNA中克隆了一个hsc70基因，命名为Ha hsc70。Ha hsc70基因的cDNA全长2145bp，具有一个长1965bp完整的开放阅读框，编码含654个氨基酸的Hsc70蛋白。该蛋白的理论分子量为71.6kDa，等电点为5.24。对Ha Hsc70蛋白的结构域分析结果显示，仅有一个大的HSP70结构域，无信号肽序列。比对Ha Hsc70与其它物种Hsc70的蛋白序列，结果显示Ha Hsc70与其它昆虫Hsc70的序列一致性高达90％以上，与高等哺乳动物及人Hsc70的序列一致性也达80％以上，与植物Hsc70、微生物Hsp70的序列一致性分别有70％及45％左右，说明Hsc70在进化上的确非常保守。
综上所述，本文首次克隆了棉铃虫的一个caspase基因，Ha caspase-1，序列分析及比对结果显示，Ha caspase-1是一个下游的effector caspase。Ha caspase-1在棉铃虫幼虫不同发育阶段的表达模式，及其在体内、体外均可被RH-2485和20E诱导上升表达的结果，提示Ha caspase-1可能受蜕皮激素上调，在棉铃虫的蜕皮及变态发育中发挥作用。Ha caspase-1在凋亡细胞中的高表达，证实了其effector caspase的功能。本文还首次克隆了棉铃虫的一个hsp基因，Ha hscT0，序列分析及比对结果显示，Ha hsc70与其它物种hsc70高度同源，对Ha hsc70的表达及功能等尚在研究之中。
细胞凋亡在生物体生长发育、细胞增殖与分化中发挥重要作用，Caspase是细胞凋亡途径中关键的作用因子，Hsps参与细胞凋亡调控，而且Caspase与Hsps之间存在相互作用。对棉铃虫Ha caspase-1和Ha hsc70基因性质、表达及功能进行研究，在此基础上研制安全性较高的抑制害虫生长发育的新型生物农药，对于发展棉铃虫防治的新方法及新途径具有重要意义。另一方面，通过对Ha caspase-1和Ha hsc70基因功能及其调控的研究，也可以进一步了解细胞凋亡发生发展的机制，从而阐明昆虫变态发育中的分子生物学机理。
The cotton bollworm, Helicoverpa armigera, which belongs to Lepidoptera Noctuidae, distributes broadly in the world and harms a lot of crops including cotton, cereal, corn, potato, bean and tobacco leaf. The cotton bollworm is one of the major pests of the world agriculture, which often brings great lost in economy. At the present time, the majority chemical pesticides used to prevent cotton bollworm are harmful to human and environment, and there is controversy on the security of the transgene crops such as the Bt cotton. Therefore, development of the biological pesticides based on the theory studies is always the focus of the pest prevention.
Apoptosis, or programmed cell death (PCD), a process of cell suicide, which eliminates superfluous, damaged or deleterious cells during development, cell differentiation, and disease to maintain homeostasis, is essential to the development of organisms. In this study, two genes, Ha caspase-1 and Ha hsc70, involved in apoptosis were cloned from H. armigera. Sequences of the genes and the deduced proteins were analyzed, and the expression pattern, induction expression and function of Ha caspase-1 were investigated. 1. Cloning and expression of Ha caspaase-1 from H. armigera
Caspase (cysteinylaspartate specific proteinase) is a group of cysteine proteinase with substrate specificity at aspartate, which is the key factor in apoptosis and has non-apoptotic functions in cell survival, proliferation and differentiation. The proteins of caspase family are evolutionally conserved, executing the similar function in apoptosis. The caspases involved in apoptosis are divided into two groups according to the sequences of their N terminal domain named prodomain. The caspases with long prodomain are the initiator caspases which transfer the signals of apoptosis and activate the downstream caspases, while the caspsaes with short prodomain are the effector caspases which cleavage the substrates in cell and are the direct executioners of apoptosis.
In this study, a caspase gene named Ha caspase-1 was cloned from the cDNA library of metamorphically committed H. armigera using the strategy of homologous cloning. The full-length of Ha caspase-1 cDNA is 1350 bp, including an 885 bp open reading frame (ORF) that encodes 294 amino acids. The deduced protein has a computed molecular mass of 33.5 kDa and a predicted isoelectric point of 5.65. Sequence analysis of the domain and active site shows that the protein has two domains, caspase-p20 and caspase-p10, which are the large subunit and the small subunit, respectively. In addition, the predicted protein contains the typical residues His and Cys required for catalysis by caspases and the catalytic cysteine (C_(176)) located in a QACQG pentapeptide is an example. Sequence alignment of amino acids of Ha caspase-1 with other known caspases revealed that it has a short prodomian and is great homologous to Sf caspase-1of Spodoptera frugiperda and drICE of Drosophila melanogaster. The homology of Ha caspase-1 to human caspase-3 is even 32%. These results suggested that Ha caspase-1 is an effector caspase in downstream of caspase cascade.
Northern blot analysis and semi-quantitative RT-PCR were used to investigate the expression pattern of Ha caspase-1 in different larval tissues. The result of Northern blot showed that the Ha caspase-1 mRNA was only detected in the feeding and wandering larval haemocytes, with the concentration in haemocytes of wandering larvae slightly higher than that in haemocytes of feeding ones. There was no positive signal detected in the epidermis, midgut, fat body from both feeding and wandering larvae, suggesting that either the expression of Ha caspase-1 mRNA was probably haemocyte-specific or its mRNA concentration in haemocytes was significantly higher than that of the other tissues. The result of RT-PCR showed that the signal detected in haemocytes from wandering larvae was much stronger than that in feeding ones and other tissues, in agreement with that of Northern blot. However, in the feeding larval fat body and the midgut and wandering larval fat body, Ha caspase-1 was also found at lower levels, which is different from the result of Northern blot and may be due to the higher sensitivity of PCR compared with Northern blot, or haemocytes attachment or migration into fat body and midgut.
Northern blot analysis was applied to determine the developmental profiles of Ha caspase-1 mRNA levels. The results revealed that Ha caspase-1 was expressed in embryos, which is consistent with the notion that cell death is extensive during embryogenesis, but there is no Ha caspase-1 detected in younger instar larvae (lst~3rd) by whole body preparation of mRNA, which may because Ha caspase-1 mRNA level is too low to be detected in these early developmental stages. However, in later instar larval haemocytes (4th—6th instar), Ha caspase-1 mRNA concentration was higher during 4th and 5th molting and wandering stages, which appears to be correlate with the two waves of ecdysone during the periods of last larva molting and metamoephosis.
In situ hybridization was performed to locate the transcript of Ha caspaes-1 in haemocytes. Results indicated that the plasmatocytes and granulocytes in haemocytes from 6th instar wandering larvae released extensive Ha caspase-1 signal. Other cells, including prohaemocytes and spherulocytes, did not show obvious signal compared with the negative control cells. The expression of Ha caspase-1 in these two kinds of haemocytes suggested that Ha caspase-1 may be involved in the larval-pupal metamorphosis because the populations of both plasmatocytes and granulocytes increased in the late stage of the last instar larvae.
Because Ha caspase-1 mRNA levels increased in haemocytes during molting and metamoephosis, it is inferred that Ha caspase-1 should be regulated by 20-hydroxyecdysone (20E). Therefore, the relationship between Ha caspase-1 and ecdysone was measured through Northern blot analysis and RT-PCR. Results showed that Ha caspase-1 expression increased in haemocytes in vivo after ecdysone agonist RH-2485 injection and Ha caspase-1 mRNA also went up in haemocytes in vitro after treated with 20E, suggesting that Ha caspase-1 expression during development correlates to the release of ecdysone.
As an effector caspase, Ha caspase-1 should play a role in apoptosis. The morphological alterations, DNA degeneration and Ha caspase-1 expression was therefore observed in the cultured epidermis cells undergoing apoptosis induced by AcMNPV (Autographa Californica multiple nucleocapsid polyhedrovirus). After AcMNPV induction, the morphological changes on cells including chromatin condensation, membrane shrinkage and vacuole appearance and apoptotic bodies were observed. In addition, nuclear DNA presented the DNA ladder on agarose gel electrophoresis. The result of RT-PCR showed that Ha caspase-1 expression in cells induced by AcMNPV was much higher than that in the non-induced cells, indicating that Ha caspase-1 is a function factor involvd in apopotosis.
In addition, a fragment containing ORF of Ha caspase-1 was subcloned into prokaryotic expression vector pET-30a(+) to construct recombined plasmid Ha casp/pET-30a(+), and recombinant protein was highly expressed in E. coli strain BL21(DE3), which are to be used for function study on Ha caspase-1.
2. Cloning of Ha hsc70 from H. armigera
Heat shock protein is a group of greatly conserved proteins, which has a broad range of biochemical functions. Hsps not only play indispensable roles in the stress reaction to maintain the self-stabilization of cell and avoid the damage of cell, but also participate in apoptosis, immune regulation, tumor and infection. Hsps is a super family including a large number of members in which Hsp70 family is the most conserved and important.
In this study, a hsc70 gene named Ha hsc70 was cloned from the SMART cDNA of epidermis from the metamorphically committedally committed H. armigera using the strategy of homologous cloning. The full-length Ha hsc70 cDNA is 2145 bp, including a 1965 bp ORF that encodes 654 amino acids. The deduced protein has a computed molecular mass of 71.6 kDa and a predicted isoelectric point of 5.24. Sequence analysis shows the protein has only one large HSP70 domain without signal peptide. Sequence alignment of amino acids of Ha Hsc70 with other known Hsc70 revealed it has the greatest homology to the Hsc70 of other insects, with an identity over 90%. The identity of Ha Hsc70 to mammal and human Hsc70s also reaches 80%. The identities of Ha Hsc70 to plant and prokaryotic Hsc70s (or Hsp70s) are even about 70% and 45%, implying that Hsc70 is greatly evolutionally conserved.
In summary, we cloned a caspase gene from H. armigera , Ha caspase-1, which is a effector caspase resulted from the sequence analysis and alignment. The expression profiles of Ha caspase-1 during development and induced expression of Ha caspase-1 by RH-2485 in vivo and 20E in vitro imply that Ha caspase-lmay be up regulated by ecdysone and play a role during molting and metamorphosis. The high expression of Ha caspase-1 in the apoptotic cells approves of its function as an effector caspase. We also cloned a hsp70 gene from H. armigera, Ha hsc70, which is highly homologous to hsc70 of other species resulted from the sequence analysis and alignment. The expression and function of Ha hsc70 is under study now.
Apoptosis plays an essential role in development, cell proliferation and differentiation. Caspases are the key regulator in the apoptotic pathways, Hsps also participate in apoptosis, and the interaction exists between caspases and Hsps. To develop biological pesticides with high security based on the study of the characterization, expression and function of both caspase and Hsps is important to the exploitation of new methods for pest control. On the other hand, to study the function and regulation of genes involved in apoptosis during insect development is in favor of better understanding the mechanism of apoptosis and insect development.
引文
Abrams JM.(1999). An emerging blueprint for apoptosis in Drosophila. Trends Cell. Biol. 9, 435-440.
Abraham EG, Islam S, Srinivasan P, Ghosh AK, Valenzuela JG, Ribeiro JM, Kafatos FC, Dimopoulos G and Jacobs-Lorena M.(2004). Analysis of the Plasmodium and Anopheles transcriptional repertoire during ookinete development and midgut invasion. J. Biol. Chem. 279, 5573-5580.
Acehan D, Jiang X, Morgan DG, Heuser JE, Wang X and Akey CW.(2002).Three-dimensional structure of the apoptosome, implications for assembly,procaspase-9 binding, and activation. Mol.Cell. 9, 423-432.
Adachia T, Tomita M and Yoshizatoa K.(2005). Synthesis of prolyl 4-hydroxylase a subunit and type Ⅳ collagen in hemocytic granular cells of silkworm, Bombyx mori: Involvement of type Ⅳ collagen in self-defense reaction and metamorphosis. Matrix Biol. 24, 136-154.
Adams C and Rinne RW.(1982). Stress protein formation: gene expression and environmental interaction with evolutionary significance. Int. Rev. Cytol, 79, 305-315.
Abroad M, Srinivasula SM, Wang L, Litwack G, Fernandes-Alnemri T and Alnemri ES.(1997). Spodoptera frugiperda Caspase-1, a novel insect death protease that cleaves the nuclear immunophilin FKBP46, is the target of the baculovirus antiapoptotic protein p35. J. Bio. Chem. 272, 1421-1424.
Aldo N P, James R W and Walton W D.(1999). Sequence features and phylogenetic analysis of the stress protein Hsp90a in Chinook Salmon (Oncorhynchus tshaw-ytscha), a poikilothermic vertebrate. Biochem. Biophysical Res. Commun. 258, 784-791.
Arama E, Agapite J and Steller H.(2003). Caspase activity and a specific cytochrome C are required for sperm differentiation in Drosophila. Dev. Cell 4, 687-697.
Aravind L, Dixit VM and Koonin EV.(1999). The domains of death, evolution of apoptosis machinery. Trends Biochem. Sci. 24, 47-53.
Aravind L and Koonin E.(2002). Classification of the caspase-hemogiobinase fold, detection of new families and implications for the origin of the eukaryotic separins. Proteins 46, 355-367.
Arbeitman MN, Furlong EE, Imam F, Johnson E, Null BH, Baker BS, Krasnow MA, Scott MP, Davis RW and White KP.(2002). Gene expression during the lifecycle of Drosophila melanogaster. Science 297, 2270-2275.
Asea A, Kraefl SK, Kurt-Jones EA, Stevenson MA, Chen LB, Finberg RW, Koo GC and Calderwood SK.(2000). HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat. Med. 6, 435-442.
Ashhab Y, Alian A, Polliack A, Panet A and Yehuda DB.(2001). Two splicing variants of a new inhibitor of apoptosis gene with different biological properties and tissue distribution pattern. FEBS Lett. 495, 56-60.
Ashkenazi A and Dixit VM.(1998). Death receptors, signaling and modulation. Science 281, 1305-1308.
Baehrecke EH.(2002). How death shapes life during development. Nat. Rev. Mol. Cell. Biol. 3, 779-787.
Beere HM, Wolf BB, Cain K, Mosser DD, Mahboubi A, Kuwana T, Tailor P, Morimoto RI and Cohen GM, Green DR.(2000). Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat. Cell Biol. 2, 469-475.
Bergeron L, Perez GI, Macdonald G, Shi L, Sun Y, Jurisicova A Varmuza S, Latham KE, Flaws JA, Salter JC, Hara H, Moskowitz MA, Li E, Greenberg A, Tilly JL and Yuan J.(1998). Defects in regulation of apoptosis in caspase-2-deficient mice. Genes Dee. 12, 1304-1314.
Bertin J and DiStefano PS.(2000). The PYRIN domain, a novel motif found in apoptosis and inflammation proteins. Cell Death Differ. 7, 1273-1274.
Bideshi DK, Tan Y, Bigot Y and Federici BA.(2005). A viral caspase contributes to modified apoptosis for virus transmission. Genes & Dev. 19, 1416-1421.
Bijian K and Cybulsky AV. (2005). Stress proteins in glomerular epithelial cell injury. Contrib. Nephrol 148, 8-20.
Blanchard F, Rusiniak ME, Sharma K, Sun X, Todorov I, Castellano MM, Gutierrez C, Baumann H and Burhans WC. (2002). Targeted destruction of DNA replication protein Cdc6 by cell death pathways in mammals and yeast. Mol. Biol Cell. 13, 1536-1549.
Boatright KM and Salvesen GS. (2003). Mechanisms of caspase activation. Curr. Opin. Cell Biol. 15,725-731.
Boatright, KM, Renatus M, Scott FL, Sperandio S, Shin H, Pedersen IM, Ricci JE, Edris WA, Sutherlin DP, Green DR and Salvesen GS. (2003). A unified model for apical caspase activation. Mol. Cell. 11, 529-541.
Brancolini C, Lazarevic D, Rodriguez J and Schneider C. (1997). Dismantling cell-cell contacts during apoptosis is coupled to a caspase- dependent proteolytic cleavage of beta-catenin. J. Cell Biol 139, 759-771.
Brancolini C, Sgorbissa A and Schneider C. (1998). Proteolytic processing of the adherens junctions components beta- catenin andgamma-catenin/plakoglobin during apoptosis. Cell Death Differ. 5,1042-1050.
Brockstedt E, Rickers A, Kostka S, Laubersheimer A, Dorken B, Wittmann-Liebold B, Bommert K and Otto A. (1998). Identification of apoptosis-associated proteins in a human Burkitt lymphoma cell line. J. Biol. Chem. 273, 28057-28064.
Browne SJ, MacFarlane M, Cohen GM and Paraskeva C. (1998). The adenomatous polyposis coli protein and retinoblastoma protein are cleaved early in apoptosisand are potential substrates for caspases. Cell Death Differ. 5, 206-213.
Budihardjo I, Oliver H, Lutter M, Luo, X and Wang X. (1999). Biochemical pathways of caspase activation during apoptosis. Annu. Rev. Cell Dev. Biol. 15, 269-290.
Bump NJ, Hackett M, Hugunin M, Seshagiri S, Brady K, Chen P, Ferenz C, Franklin S, Ghayur T and Li P. (1995). Inhibition of ICE family proteases by baculovirus antiapoptotic protein p35. Science 269,1885-1888.
Cakouros D, Daish TJ, Martin D, Baehrecke EH and Kumar S.(2002).Ecdysone-induced expression of the caspase DRONC during hormone-dependent programmed cell death in Drosophila is regulated by Broad-Complex. J. Cell Biol. 157, 985-995.
Cakouros D, Daish TJ and Kumar S.(2004). Ecdysone receptor directly binds the promoter of the Drosophila caspase dronc regulating its expression in specific tissues. J. Cell. Biol. 165, 631-640.
Casciola-Rosen L, Nicholson DW, Chong T, Rowan KR, Thomberry NA, Miller DK and Rosen A.(1996). Apopain/CPP32 cleaves proteins that are essential for cellular repair, a fundamental principle of apoptotic death. J. Exp. Med. 183, 1957-1964.
Cassens U, Lewinski G, Samraj AK, yon Bernuth H, Baust H, Khazaie K and Los M. (2003). Viral modulation of cell death by inhibition of caspases. Arch. Immunol. Ther. Exp. 51, 19-27.
Catherine T, Florence D and Annie B.(2000). Molecular cloning, organellar targeting and developmental expression of mitochondrial chaperone HSP60 in Toxoplasma gondii. Mol. Biochem. Parasitology111, 319-332.
Cerretti DP, Kozlosky CJ, Mosley B, Nelson N, Van Ness K, Greenstreet TA, March CJ, Kronheim SR, Druck T and Cannizzaro LA.(1992) Molecular cloning of the interleukin-1 beta converting enzyme. Science 256, 97-100.
Chai J, Du C, Wu JW, Kyin S, Wang X, and Shi Y.(2000). Structural and biochemical basis of apoptotic activation by Smac/DIABLO. Nature 406, 855-862.
Chai J, WuQ, Shiozaki E, Srinivasula SM, Alnemri ES and Shi Y.(2001a). Crystal structure of a procaspase-7 zymogen: mechanisms of activation and substrate binding. Cell 107, 399-407.
Chai J, Shiozaki E, Srinivasula SM, Wu Q, Datta P, Alnemri ES and Shi Y.(2001b). Structural basis of caspase-7 inhibition by XIAP. Cell 104, 769-780.
Chai, J., Yan, N., Huh, J. R., Wu, J. -W., Li, W., Hay, B. A., and Shi, Y.(2003). Molecular mechanism of Reaper/Grim/Hid-mediated suppression of DIAP1dependent Dronc ubiquitination. Nat. Struct. Biol. 10, 892-898.
Chang DW, Xing Z, Capacio VL, Peter ME and Yang X.(2003). Interdimer processing mechanism of procaspase-8 activation. EMBO J. 22, 4132-4142.
Charette SJ and Landry J.(2000). The interaction of HSP27 with Daxx identifies a potential regulatory role of HSP27 in Fas-induced apoptosis. Ann. N Y Acad. Sci. 926, 126-131.
Chau BN, Borges HL, Chen TT, Masselli A, Hunton IC and Wang JY.(2002). Signal-dependent protection from apoptosis in mice expressing caspase-resistant Rb. Nat. Cell Biol. 4, 757-765.
Chen P, Rodriguez A, Erskine R, Thach T and Abrams JM.(1998). Dredd, a novel effector of the apoptosis activators reaper, grim, and hid in Drosophila. Dev. Biol. 201, 202-216
Chun HJ, Zheng L, Ahmad M, Wang J, Speirs CK, Siegel RM, Dale JK, Puck J, Davis J, Hall CG, Skoda-Smith S, Atkinson TP, Straus SE, and Lenardo MJ.(2002). Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. Nature 419, 395-399.
Cohen GM.(1999). Caspases: the executioners of apoptosis. Biochem. J. 326, 1-16.
Compton MM.(1992). A biochemical hallmark of apoptosis: intemucleosomal degradation of the genome. Cancer Metastasis Rev. 11, 105-19.
Cory S and Adams JM.(2002). The Bcl2 family, Regulators of the cellular life-or-death switch. Nat. Rev. Cancer 2, 647-656.
Crook NE, Clem RJ and Miller LK.(1993). An apoptosis-inhibiting baculovirus gene with a zinc finger-like motif. J. Virol. 67, 2168-2174.
Cryns VL, Byun Y, Rana A, Mellor H, Lustig KD, Ghanem L, Parker PJ, Kirschner MW and Yuan J.(1997). Specific proteolysis of the kinase protein kinase C related kinase 2 by caspase-3 during apoptosis: identification by a novel, small pool expression cloning strategy. J. Biol. Chem. 272, 29449-29453.
Datta R, Kojima H, Yoshida K and Kufe D.(1997). Caspase-3-mediated cleavage of protein kinase C theta in induction of apoptosis. J. Biol. Chem. 272, 20317-20320.
De Botton S, Sabri S, Daugas E, Zermati Y, Guidotti JE, Hermine O, Kroemer G, Vainchenker W and Debili N. (2002). Platelet formation is the consequence of caspase activation within megakaryocytes. Blood 100,1310-1317.
De Jong L, Moreau X, Jean S, Scher O and Thiery A. (2006). Expression of the heat shock protein Hsp70 in chloride target cells of mayfly larvae from motorway retention pond: A biomarker of osmotic shock. Sci. Total Environ. 366,164-173.
DeNagel DC and Pierce SK. (1993). Heat shock proteins in immune responses. Crit. Rev. Immunol 13, 71-81.
Degterev A, Boyce M and Yuan J. (2003). A decade of caspases. Oncogene 22, 8543-8567.
Deveraux QL and Reed JC. (1999). IAP family proteins, suppressors of apoptosis. Genes Dev. 13,239-252.
Dhadialla TS, Carlson GR and Le DP. (1998). New insecticides with ecdysteroidal and juvenile hormone activity. Annu. Rev. Entomol. 43, 545-569.
Donepudi M, Mac Sweeney A, Briand C and Grutter MG. (2003). Insights into the regulatory mechanism for caspase - 8 activation. Mol. Cell 11, 543 -549.
Dorstyn L, Colussi PA, Quinn LM, Richardson H and Kumar S. (1999). DRONC, an ecdysone inducible Drosophila caspase. Proc. Natl. Acad. Sci. USA 96,4307-4312.
Dorstyn L, Colussi PA, Quinn LM, Richardson H and Kumar S. (1999). DRONC, an ecdysone-inducible Drosophila caspase. Proc.Natl Acad. Sci. 13, 4307-4312.
Dorstyn L and Kumar S. (2006). A cytochrome c-free fly apoptosome. Cell Death Differ. 13,1049-1051.
Doumanis J, Quinn L, Richardson H and Kumar S. (2001). STRICA, a novel Drosophila caspase with an unusual serine/threonine-rich prodomain, interacts with DIAP1 and DIAP2. Cell Death Differ. 8,387-394.
Du C, Fang M, Li Y and Wang X. (2000). Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation during apoptosis. Cell 102, 33-42.
Dunlap DY and Matsumura F. (1997). Development of broad spectrum antibodies to heat shock protein 70s as biomarkers for detection of multiple stress by pollutants and environmental factors. Ecotoxicol Environ. Saf. 37, 238-244.
Earnshaw WC, Martins LM and Kaufmann SH. (1999). Mammalian caspases: Structure, activation, substrates, and functions during apoptosis. Annu. Rev. Biochem. 68,383-424.
Eckhart L, Ballaun C, Uthman A, Kittel C, Stichenwirth M, Buchberger M, Fischer H, Sipos W, and Tschachler E (2005). Identification and characterization of a novel mammalian caspase with proapoptotic activity. J.Bio.Chem. 280, 35077-35080.
Ellis RE, Yuan JY and Horvitz HR. (1991). Mechanisms and functions of cell death. Annu. Rev. Cell. Biol. 7,663-698.
Fernandes-Alnemri T, Litwack G and Alnemri ES. (1994). CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1P-converting Enzyme. J.Biol.Chem. 269,49-53.
Fernandes-Alnemri T, Armstrong R and Krebs J. (1996). In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains. Proc. Natl. Acad. Sci. USA 93, 7464-7469.
Fernando P, Kelly JF, Balazsi K, Slack RS and Megeney LA. (2002). Caspase 3 activity is required for skeletal muscle differentiation. Proc. Natl. Acad. Sci. USA 99, 11025-11030.
Fesik SW and Shi Y. (2001). Controlling caspases. Science 294,1477-1478.
Fischer U, Janicke RU and Schulze-Osthoff K. (2003). Many cuts to ruin, a comprehensive update of caspase substrates. Cell Death Differ. 10,76-100.
Fraser AG and Evan GI. (1997). Identification of a Drosophila melanogaster ICE/CED-3- related protease, drICE. EMBO J 16,2805-2813.
Fraser AG, McCarthy NJ and Evan GI. (1997). drICE is an essential caspase required for apoptotic activity in Drosophila cells. EMBO J. 16, 6192-6199.
Frost V, Delikat S, Al-Mehairi S and Sinclair AJ.(2001). Regulation of p27KIP1 in Epstein-Barr virus immortalized lymphoblastoid cell lines involves non-apoptotic caspase cleavage. J. Gen. Virol. 82, 3057-3066.
Frutos S, Moscat J and Diaz-Meco MT.(1999). Cleavage of zetaPKC but not lambda/iotaPKC by caspase-3 during UV-induced apoptosis. J. Biol. Chem. 274, 10765-10770.
Geisbrecht ER and Montell DJ.(2004). A role for Drosophila IAP1-mediated caspase inhibition in Rac-dependent cell migration. Cell 118, 111-125.
Germain M, Affar EB, D'Amours D, Dixit VM, Salvesen GS and Poirier GG.(1999).
Cleavage of automodified Poly(ADP-ribose) polymerase during apoptosis. Evidence for involvement of caspase-7. J. Biol. Chem. 274, 28379-28384.
Golks A, Brenner D, Fritsch C, Krammer PH and Lavrik IN.(2005). C-FLIPR, a new regulator of death receptor-induced apoptosis. J. Biol. Chem. 280, 14507-14513.
Gordon SA, Hoffman RA, Simmons RL and Ford HR.(1997). Induction of heat shock protein 70 protects thymocytes against radiation-induced apoptosis. Arch. Surg. 132, 1277-1282.
Gueth-Hallonet C, Weber K and Osborn M.(1997). Cleavage of the nuclear matrix protein NuMA during apoptosis. Exp. Cell. Res. 233, 21-24.
Hakem R, Hakem A, Duncan GS, Henderson JT, Woo M, Soengas MS Elia A, de la Pompa JL, Kagi D, Khoo W, Potter J, Yoshida R, Kaufman SA, Lowe SW, Penninger JM and Mak TW. (1998). Differential requirement for caspase-9 in apoptotic pathways in vivo. Cell 94, 339-352.
Harris JL, Backes BJ, Leonetti F, Mahrus S, Ellman JA and Craik CS. (2000). Rapid and general profiling of protease specificity by using combinatorial fluorogenic substrate libraries. Proc. Natl. Acad. Sci. USA 97, 7754-7759.
Hartl FU.(1996). Molecular chaperones in cellular protein folding. Nature 381, 571-579.
Harvey NL, Daish T, Mills K, Dorstyn L, Quinn LM, Read SH, Richardson H and Kumar S. (2001). Characterization of the Drosophila caspase, DAMM. J. Biol. Chem. 276, 25342-25350.
Hatsugai N, Kuroyanagi M, Yamada K, Meshi T, Tsuda S, Kondo M, Nishimura M and Hara-Nishimura I. (2004). A plant vacuolar protease, VPE, mediates virus-induced hypersensitive cell death. Science 305, 855-858.
Hatsugai N, Kuroyanagi M, Nishimura M and Hara-Nishimura I. (2006). A cellular suicide strategy of plants: vacuole-mediated cell death. Apoptosis 11, 905-911.
Hawkins CJ, Wang SL and Hay BA. (1999). A cloning method to identify caspases and their regulators in yeast, identification of Drosophila IAPl as an inhibitor of the Drosophila caspase DCP-1.Proc. Natl. Acad. Sci. USA 96, 2885-2890.
Hawkins CJ, Yoo SJ, Peterson EP, Wang SL, Vernooy SY and Hay BA. (2000). The Drosophila caspase DRONC is a glutamate/aspartate protease whose activity is regulated by DIAP1, HID and GRIM. J. Biol. Chem. 275, 27084-27093.
Hay BA, Wassarman DA and Rubin GM. (1995). Drosophila homologs of baculovirus inhibitor of apoptosis proteins function to block cell death. Cell 83, 1253-1262.
Hays R, Wickline L and Cagan R. (2002). Morgue mediates apoptosis in the Drosophila melanogaster retina by promoting degradation of DIAP1. Nat.Cell Biol. 4, 425-431.
Heifer B, Boswell BC, Finlay D, Cipres A, Vuori K, Bong Kang T, Wallach D, Dorfleutner A, Lahti JM, Flynn DC and Frisch SM. (2006). Caspase-8 promotes cell motility and calpain activity under nonapoptotic conditions. Cancer Res. 66, 4273-4278.
Herrmann M, Lorenz HM, Voll R, Grunke M, Woith W and Kalden JR. (1994). A Rapid and simple method for the isolation of apoptotic DNA fragments. Nucleic. Acid Res. 22, 5506-5507.
Horvitz HR. (2003). Worms, life, and death. Chembiochem. 4, 697-711.
Hsu HL and Yeh NH. (1996). Dynamic changes of NuMA during the cell cycle and possible appearance of a truncated form of NuMA during apoptosis. J.Cell. Sci. 109, 277-288.
Hu S and Yang X. (2000). dFADD, a novel death domain-containing adapter protein for the Drosophila caspase DREDD. J. Biol. Chem. 275, 30761-30764.
Huang Y, Park YC, Rich RL, Segal D, Myszka DG and Wu H. (2001). Structural basis of caspase inhibition by XIAP, differential roles of the Linker versus the BIR domain. Cell 104, 781-790.
Huh JR, Guo M and Hay BA. (2004). Compensatory proliferation induced by cell death in the Drosophila wing disc requires activity of the apical cell death caspase Dronc in a nonapoptotic role. Curr. Biol. 14,1262-1266.
Inohara N, Koseki T, Hu Y, Chen S and Nunez G. (1997). CLARP, a death effector domain containing protein interacts with caspase-8 and regulates apoptosis. Proc. Natl. Acad. Sci. USA 94,10717-10722.
Jiang C, Lamblin AF, Steller H and Thummel CS. (2000). A steroid-triggered transcriptional hierarchy controls salivary gland cell death during Drosophila metamorphosis. Mol. Cell 5,445-55.
Jiang X and Wang X. (2000). Cytochrome c promotes caspase-9 activation by inducing nucleotide binding to Apaf-1. J. Biol. Chem. 275,31199-31203.
Kang TB, Ben-Moshe T, Varfolomeev EE, Pewzner-Jung Y, Yogev N, Jurewicz A, Waisman A, Brenner O, Haffner R, Gustafsson E, Ramakrishnan P, Lapidot Tand Wallach D. (2004). Caspase-8 serves both apoptotic and nonapoptotic roles. J. Immunol. 173, 2976-2984.
Kasof GM and Gomes BC. (2001). Livin, a novel inhibitor of apoptosis protein family member. J. Biol. Chem. 276,3238-3246.
Kato D, Boatright KM, Berger AB, Nazif T, Blum G, Ryan C Chehade KA, Salvesen GS and Bogyo M. (2005). Activity-based probes that target diverse cysteine protease families. Nature Chem. Biol. 1, 33-38.
Kanuka H, Sawamoto K, Inohara N, Matsuno K, Okano H and Miura M.(1999).Control of the cell death pathway by Dapaf-1, a Drosophila Apaf-1/CED-4-related caspase activator. Mol. Cell 4, 757-769.
Khwaja A and Tatton L.(1999). Caspase-mediated proteolysis and activation of protein kinase Cdelta plays a central role in neutrophil apoptosis. Blood 94, 291-301.
Kilpatrick ZE, Cakouros D and Kumar S.(2005). Ecdysone-mediated up-regulation of the erector caspase DRICE is required for hormone-dependent apoptosis in Drosophila cells. J. Biol. Chem. 280, 11981-11986.
Kim YM, de Vera ME, Watkins SC and Billiar TR.(1997). Nitric oxide protects cultured rat hepatocytes from tumor necrosis factor-alpha-induced apoptosis by inducing heat shock protein 70 expression. J. Biol. Chem. 272, 1402-1411.
Kischkel FC, Hellbardt S, Behrmann I, Germer M, Pawlita M, Krammer PH and Peter ME. (1995). Cytotoxicity-dependent APO-1(Fas/CD95)-associated proteins form a death-inducing signaling complex(DISC) with the receptor. EMBO J. 14, 5579-5588.
Kischkel FC, Lawrence DA, Tinel A, LeBlanc H, Virmani A, Schow P, Gazdar A, Blenis J, Amott D and Ashkenazi A.(2001). Death receptor recruitment of endogenous caspase-10 and apoptosis initiation in the absence of caspase-8. J. Biol. Chem. 276, 46639-46646.
Kita T.(2000). The role of heat shock proteins on the disordered tissues: implication for the pathogenesis and diagnostics in the forensic practice, Nippon Hoigaku Zasshi 54, 367-371.
Kobayashi K, Inohara N, Hemandez LD, Galan JE, Nunez G, Janeway CA, Medzhitov R and Flavell RA.(2002). RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems. Nature 416, 194-199.
Ko"hler H R, Belitz B, Eckwert H, Adam R, Rahman B and Tronteli P. Validation of Hsp70 stress gene expression as a marker of metal effects in Deroceras reticulatum (Pulmonata): correlation with demographic parameters. Environ. Toxicol. Chem. 17, 2246-2253.
Kondo S, Senoo-Matsuda N, Hiromi Y and Miura M.(2006). DRONC coordinates cell death and compensatory proliferation. Mol. Cell Biol. 26,7258-7268.
Korsmeyer SJ, Wei MC, Saito M, Weiler S, Oh KJ and Schlesinger PH. (2000). Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c. Cell Death Differ. 7,1166-1173.
Kothakota S, Azuma T, Reinhard C, Klippel A, Tang J, Chu K, McGarry TJ, Kirschner MW, Koths K, Kwiatkowski DJ and Williams LT. (1997). Caspase-3-generated fragment of gelsolin, effector of morphological change in apoptosis. Science 278,294-298.
Krueger A, Schmitz I, Baumann S, Krammer PH and Kirchhoff S. (2001). Cellular flice-inhibitory protein splice variants inhibit different steps of caspase-8 activation at the cd95 death-inducing signaling complex. J. Biol Chem. 276, 20633-20640.
Kuida K, Zheng TS, Na S, Kuan C, Yang D, Karasuyama H, Rakic P and Flavell RA.(1996). Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice. Nature 384,368-372.
Kuida K, Haydar TF, Kuan C-Y, Gu Y, Taya C, Karasuyama H Su MS, Rakic P and Flavell RA. (1998). Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9. Cell 94,325-337.
Kumar S and Doumanis J. (2000). The fly caspases. Cell Death Differ. 7,1039-1044.
Kumar S and Cakouros D. (2004). Transcriptional control of the core cell-death machinery. Trends Biochem. Sci. 29,193-199.
LaCount DJ, Hanson SF, Schneider CL and Friesen PD. (2000). Caspase inhibitor P35 and inhibitor of apoptosis Op-IAP block in vivo proteolytic activation of an effector caspase at different steps. J. Biol. Chem. 275,15657 -15664.
Laemmli UK. (1970). Cleavage of structural proteins during the assemble of the head of bacteriophage T4. Nature 227, 680-685.
Lakhani SA, Masud A, Kuida K, Porter Jr GA, Booth CJ, Mehal WZ, Inayat I and Flavell RA. (2006). Caspases 3 and 7, key mediators of mitochondrial events of apoptosis. Science 311, 847-851.
Lamkanfi M, D'Hondt K, Vande Walle L, Van Gurp M, Denecker G, Demeulemcester J, Kalai M, Declercq W, Saelens X and Vandenabeele P.(2005). Anovel caspase-2 complex containing TRAF2 and RIP1. J. Biol. Chem. 280, 6923-6932.
Lamkanfi M, Festjens N, Declercq W, Vanden Berghe T and Vandenabeele P.(2007). Caspases in cell survival, proliferation and differentiation. Cell Death Differ. 14, 44-55.
Lavrik I, Krueger A, Schmitz I, Baumann S, Weyd H, Krammer PH and Kirchhoff S. (2003). The active caspase-8 heterotetramer is formed at the CD95 DISC. Cell Death Differ. 10, 144-145.
Lavrik IN, Golks A, and Krammer PH.(2005). Caspases, pharmacological manipulation of cell death. J. Clin. Invest. 115, 2665-2672.
Lee CY, Cooksey BA and Baehrecke EH.(2002). Steroid regulation of midgut cell death during Drosophila development. Dev. Biol. 250, 101-111.
Leulier F, Rodriguez A, Khush RS, Abrams JM and Lemaitre B.(2000). The Drosophila caspase Dredd is required to resist gram-negative bacterial infection. EMBO Rep 1, 353-358.
Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES and Wang X. (1997). Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91, 479-489.
Lockshin RA and Zakeri Z.(2001). Programmed cell death and apoptosis: origins of the theory. Nat. Rev. Mol. Cell, Biol. 2, 545-550.
Mahroof R, Zhu KY, Neven L, Subramanyam B and Bai J.(2005). Expression patterns of three heat shock protein 70 genes among developmental stages of the red flour beetle, Tribolium castaneum(Coleoptera: Tenebrionidae). Comp. Biochem. Physiol. 141, 247-256.
Martin J and Hartl FU.(1997). Chaperone assisted protein folding. Curr. Opinion in Struct. Biol., 7, 41-52.
Martin SJ, Amarante-Mendes GP, Shi L, Chuang TH, Casiano CA, O'Brien GA, Fitzgerald P, Tan EM, Bokoch GM, Greenberg AH, and Green DR. (1996). The cytotoxic cell protease granzyme B initiates apoptosis in a cell-free system by proteolytic processing and activation of the ICE/CED-3 family protease, CPP32, via a novel two-step mechanism. EMBO J. 15,2407-2416.
Martin DA, Siegel RM, Zheng L and Lenardo MJ. (1998). Membrane oligomerization and cleavage activates the caspase-8 (FLICE/MACHalpha1) death signal. J. Biol. Chem. 273, 4345-4349.
Martinon F and Tschopp J. (2004). Inflammatory caspases, linking an intracellular innate immune system to autoinflammatory diseases. Cell. 117, 561-574.
Meier P, Silke J, Leevers SJ and Evan GI. (2000). The Drosophila caspase DRONC is regulated by DIAPI. EMBO J. 19,598- 611.
Micheau O, Thome M, Schneider P, Holler N, Tschopp J, Nicholson DW, Briand C and Grutter MG. (2002). The long form of FLIP is an activator of caspase-8 at the Fas death-inducing signaling complex. J. Biol. Chem. 277, 45162-45171.
Milhas D, Cuvillier O, Therville N, Clave P, Thomsen M, Levade T Benoist H and Segui B. (2005). Caspase-10 triggers Bid cleavage and caspase cascade activation in FasL-induced apoptosis. J. Biol. Chem. 280,19836-19842.
Mills K, Daish T and Kumar S. (2005). The function of the Drosophila caspase DRONC in cell death and development. Cell Cycle 4, 744-746.
Mills K, Daish T, Harvey KF, Pfleger CM, Hariharan IK and Kumar S. (2006). The Drosophila melanogaster Apaf-1 homologue ARK is required for most, but not all, programmed cell death. J. Cell Biol. 172, 809-815.
Miura M, Chen XD, Allen MR, Bi Y, Gronthos S, Seo BM, Lakhani S, Flavell RA, Feng XH, Robey PG, Young M and Shi S. (2004). A crucial role of caspase-3 in osteogenic differentiation of bone marrow stromal stem cells. J. Clin. Invest. 114, 1704-1713.
Moseley PL. (1997). Heat shock proteins and heat adaptation of the whole organism. J. Applied Physiol. 83,1413-1 417.
Mosser DD, Caron AW, Bourget L, Meriin AB, Sherman MY, Morimoto RI and Massie B. (2000). The chaperone function of Hsp70 is required for protection against stress-induced apoptosis. Mol Cell Biol 20,7146-7159.
Muller F, Adori C and Sass M. (2004). Autophagic and apoptotic features during programmed cell death in the fat body of the tobacco hornworm (Manduca sexta). Eur. J. Cell Biol 83, 67-78.
Multhoff G (2006). Heat shock proteins in immunity. Handb. Exp. Pharmacol 172, 279-304.
Muro I, Berry DL, Huh JR, Chen CH, Huang H, Yoo SJ, Guo M, Baehrecke EH and Hay BA. (2006). The Drosophila caspase Ice is important for many apoptotic cell deaths and for spermatid individualization, a nonapoptotic process. Development 133, 3305-3315.
Muzio M, Stockwell BR, Stennicke HR, Salvesen GS and Dixit VM. (1998). An Induced proximity model for caspase-8 activation. J.Bio.Chem. 273, 2926-2930.
Nicholson DW. (1999). Caspase structure, proteolytic substrates, and function during apoptotic cell death. Cell Death Differ. 6,1028-1042.
Parthasarathy R and Palli SR. (2007). Developmental and hormonal regulation of midgut remodeling in a lepidopteran insect, Heliothis virescens. Mech. Dev. 124, 23-34.
Pei Z, Reske G, Huang Q, Hammock BD, Qi Y and Chejanovsky N. (2002). Characterization of the apoptosis suppressor protein P49 from the Spodoptera littoralis nucleopolyhedrovirus. J. Biol. Chem. 277, 677-684.
Petrilli V, Herceg Z, Hassa PO, Patel NS, Di Paola R, Cortes U, Dugo L, Filipe HM, Thiemermann C, Hottiger MO, Cuzzocrea S, and Wang ZQ. (2004). Noncleavable poly(ADP-ribose) polymerase-1 regulates the inflammation response in mice. J. Clin. Invest. 114,1072-1081.
Plowman JE, Bryson WG and Jordan TW. (2000). Application of proteomics for determining protein markers for wool quality traits. Electrophoresis 21,1899-1906.
Porter AG and Janicke RU.(1999). Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 6, 99-104.
Quinn LM, Dorstyn L, Mills K, Colussi PA, Chen P, Coombe M, Abrams J, Kumar S and Richardson H.(2000). An essentialrole for the caspase Dronc in developmentally programmed cell death in Drosophila. J. Biol. Chem. 275, 40416-40424.
Rao L, Perez D and White E.(1996). Lamin proteolysis facilitates nuclear events during apoptosis. J. Cell. Biol. 135, 1441-1455.
Riddiford LY, Hiruma K, Zhou X and Nelson CA.(2003). Insights into the molecular basis of the hormonal control of molting and metamorphosis from Manduca sexta and Drosophila melanogaster. Insect Biochem. Mol. Bio. 33, 1327-1338.
Riedl SJ, Renatus M, Schwarzenbacher R, Zhou Q, Sun C, Fesik SW, Liddington RC and Salvesen GS.(2001b). Structural basis for the inhibition of caspase-3 by XIAP. Cell 104, 791-800.
Rinehart JP, YocumGD and Denlinger DL.(2000). Developmental upregulation of inducible hsp70 transcripts, but not the cognate form, during pupal diapause in the flesh fly, Sarcophaga crassipalpis. Insect Biochem. Mol. Biol. 30, 515-521.
Rinehart JP, Hayward SAL, Elnitsky MA, Sandro LH, Lee RE and Denlinger DL. (2006). Continuous up-regulation of heat shock proteins in larvae, but not adults, of a polar insect. Proc. Natl. Acad. Sci. USA 103, 14223-14227.
Ritossa FM.(1962). A new puffing pattern induced by heat shock and DNP in Drosophilia. Experientia, 18, 571-573.
Rodriguez A, Oliver H, Zou H, Chen P, Wang X and Abrams JM.(1999). Dark is a Drosophila homologue of Apaf-1/CED-4 and functions in an evolutionarily conserved death pathway. Nat. Cell Biol. 1, 272-279.
Rojo E, Martin R, Carter C, Zouhar J, Pan S, Plotnikova J, Jin H, Paneque M, Sanchez-Serrano JJ, Baker B, Ausubel FM and Raikhel NV.(2004). VPEgamma exhibits a caspase-like activity that contributes to defense against pathogens. Curr. Biol. 14, 1897-1906.
Rotonda J, Nicholson DW, Fazil KM, GallantM, Gareau Y, Labclle M, Pcterson EP, Rasper DM, Rucl R, Vaillancourt JP, Thornbcrry NA and Bcckcr JW. (1996). The three-dimensional structure of apopain/CPP32, a key mediator of apoptosis. Nat. Struct. Biol. 3, 619-625.
Rybczynski R and Gilbert LI.(2000). cDNA cloning and expression of a hormoneregulated heat shock protein(hsc 70) from the prothoracic gland of Manduca sexta. Insect Biochem. Mol. Biol. 30, 579-589.
Sakahira H, Enari M and Nagata S.(1998). Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis. Nature 391, 96-99.
Salch A, Srinivasula SM, Balkir L, Robbins PD and Alncmri ES.(2000). Negative regulation of the Apaf-1 apoptosomc by Hsp70. Nat. Cell Biol. 2, 476-483.
Salmena L, Lemmers B, Hakem A, Matysiak-Zablocki E, Murakami K, Au PY, Berry DM, Tamblyn L, Shehabeldin A, Migon E, Wakeham A, Bouchard D, Yeh WC, McGlade JC, Ohashi PS, and Hakem R.(2003). Essential role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity. Genes Dev. 17, 883-895.
Sambrook J et al., (1989) 《分子克隆》第三版.
Saraste A and Pulkki K.(2000). Morphologic and biochemical hallmarks of apoptosis. Cardiovasc Res. 45, 528-537.
Scaffidi C, Medema JP, Krammer PH and Peter ME.(1997). FLICE is predominantly expressed as two functionally active isoforms, caspase-8/a and caspase-8/b. J. Biol. Chem. 272, 26953-26958.
Scaffidi C, Kischkel FC, Krammer PH and Peter ME. 1999a. Analysis of the CD95 (APO-1/Fas) death-inducing signaling complex(DISC) by high resolution two-dimensional gel electrophoresis. Methods Enzymol. 322, 363-373.
Scaffidi C, Krammer PH and Peter ME.(1999b). Isolation and analysis of components of CD95(APO-1/Fas) death-inducing signaling complex. Methods. 17, 287-291.
Scaffidi C, Schmitz I, Krammer PH and Peter ME.(1999c). The role of c-FLIP in modulation of CD95-induced apoptosis. J. Biol. Chem. 274, 1541-1548.
Schlesinger MJ.(1990). Heat shock proteins. J. Biol. Chem. 265, 12111-12114.
Schwab BL, Leist M, Knippers R and Nicotera P.(1998). Selective proteolysis of the nuclear replication factor MCM3 in apoptosis. Exp. Cell. Res. 238, 415-421.
Shi Y.(2001). A structural view of mitochondria-mediated apoptosis. Nat. Struct. Biol. 8, 394-401.
Shi Y.(2005). Caspase activation, inhibition, and reactivation, A mechanistic view. Protein Science 13, 1979-1987.
Song Q, Lees-Miller SP, Kumar S, Zhang Z, Chan DW, Smith GC, Jackson SP, Alnemri ES, Litwack G, Khanna KK and Lavin MF.(1996). DNA-dependent protein kinase catalytic subunit, a target for an ICE-like protease in apoptosis. EMBO J. 15, 3238-3246.
Song Z, McCall K and Steller H.(1997). DCP-1, a Drosophila cell death protease essential for development. Science 275, 536-540.
Sordet O, Rebe C, Plenchette S, Zermati Y, Hermine O, Valnchenker W, Garrido C, Solar3/E and Dubrez-Daloz L.(2002). Specific involvement of caspases in the differentiation of monocytes into macrophages. Blood 100, 4446-4453.
Sprick MR, Rieser E, Stahl H, Grosse-Wilde A, Weigand MA and Walczak H. (2002). Caspase-10 is recruited to and activated at the native TRAIL and CD95 death-inducing signaling complexes in a FADD-dependent manner but can not functionally substitute caspase-8. EMBO J. 21, 4520-4530
Srinivasula SM, Hegde R, Saleh A, Datta P, Shiozaki E, Chai J, Lee RA, Robbins PD, Fernandes-Alnemri T, Shi Y and Alnemri ES.(2001a). A conserved XIAP interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature 410, 112-116.
Srinivasula SM, Saleh A, Hedge R, Datta P, Shiozaki EJ, Robbins PD, Fernandes-Alnemri T, Shi Y and Alnemri ES. (2001b). A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO mediates opposing effects on caspase activity and apoptosis. Chem. Biol. 7,423-432.
Stennicke HR, Renatus M, Meldal M and Salvesen GS. (2000). Internally quenched fluorescent peptide substrates disclose the subsite preferences of human caspases 1, 3, 6,7 and 8. Biochem J. 350,563-568.
Stennicke HR and Salvesen GS. (1999). Caspases: preparation and characterization. Methods. 17,313-319.
Stennicke HR, Ryan CA and Salvesen GS. (2002). Reprieval from execution, the molecular basis of caspase inhibition. Trends Biochem. Sci. 27, 94-101.
Stoven S, Silverman N, Junell A, Hedengren-Olcott M, Erturk D, Engstrom Y, Maniatis T, and Hultmark D. (2003). Caspase-mediated processing of the Drosophila NF-kappaB factor relish. Proc. Natl. Acad. Sci. USA 100,5991-5996.
Suarez MF, Filonova LH, Smertenko A, Savenkov EI, Clapham DH, von Arnold S, Zhivotovsky B and Bozhkov PV. (2004). Metacaspase-dependent programmed cell death is essential for plant embryogenesis. Curr. Biol. 14, 339-340.
Takahashi A, Alnemri ES, Lazebnik YA, Fernandes-Alnemri T, LitwackG, Moir RD, Goldman RD, Poirier GG, Kaufmann SH and Earnshaw WC. (1996). Cleavage of lamin A by Mch2 alpha but not CPP32, multiple interleukin 1 beta converting enzyme-related proteases with distinct substrate recognition properties are active in apoptosis. Proc. Natl. Acad. Sci. USA 93, 8395-8400.
Tang D and Kidd VJ. (1998). Cleavage of DFF-45/ICAD by multiple caspases is essential for its function during apoptosis. J. Biol. Chem. 273,.28549-28552.
Tartaglia LA, Ayres TM, Wong GH and Goeddel DV. (1993). A novel domain within the 55 kd TNF receptor signals cell death. Cell 74, 845-853.
Tesco G, Kim TW, Diehlmann A, Beyreuther K and Tanzi RE. (1998). Abrogation of the presenilin 1/beta-catenin interaction and preservation of the heterodimeric presenilin 1 complex following caspase activation. J. Biol. Chem. 273, 33909-33914.
Tewari M, Quan LT, O'Rourke K, Desnoyers S, Zeng Z, Beidler DR, Poirier GG, Salvesen GS and Dixit VM. (1995). Yama/CPP32-beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly (ADP-ribose) polymerase. Cell 81, 801-809.
Thornberry NA, Bull HG, Calaycay JR, Chapman KT, Howard AD, Kostura MJ, Miller DK, Molineaux SM, Weidner JR and Aunins J. (1992). A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature 356, 768-774.
Thummel CS. (2001). Steroid-triggered death by autophagy. BioEssays 23, 677-682.
Timmer JC and Salvesen GS. (2007). Caspase substrates. Cell Death and Differ. 14, 66-72.
Tinel A and Tschopp J. (2004). The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress. Science 304,.843-846.
Tissieres A, Mitchell HK and Tracy UM. (1974). Protein synthesis in salivary glands of Drosophila melanogaster: Relation to chromosome puffs. J. Mol. Biol. 85,389-398.
Truman JW and Riddiford LM. (2002). Endocrine insights into the evolution of metamorphosis in insects. Annu. Rev. Entomol. 47, 467-500.
Varfolomeev EE, Schuchmann M, Luria V, Chiannilkulchai N, Beckmann JS, Mett IL Rebrikov D, Brodianski VM, Kemper OC, Kollet O, Lapidot T, Soffer D, Sobe T, Avraham KB, Goncharov T, Holtmann H, Lonai P and Wallach D. (1998). Targeted disruption of the mouse caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally. Immunity 9,267-276.
Varfolomeev EE, Maecker H, Sharp D, Lawrence D, Renz M, Vucic D and Ashkenazi A. (2005). Molecular determinants of kinase pathway activation by Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand. J. Biol. Chem. 280, 40599-40608.
Verhagen AM, Ekert PG, Pakusch M, Silke J, Connolly LM, Reid GE, Moritz RL, Simpson RJ and Vaux DL. (2000). Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing LAP proteins. Cell 102,43-53.
Vucic D, Stennicke HR, Pisabarro MT, Salvesen GS and Dixit VM. (2000). ML-IAP, a novel inhibitor of apoptosis that is preferentially expressed in human melanomas. Curr. Biol. 10, 1359-1366.
Wallin RP, Lundqvist A, More SH, von Bonin A, Kiessling R and Ljunggren HG. (2002). Heat-shock proteins as activators of the innate immune system. Trends Immunol. 23, 130-135.
Walter BN, Huang Z, Jakobi R, Tuazon PT, Alnemri ES, Litwack G and Traugh JA. (1998). Cleavage and activation of p21-activated protein kinase gamma-PAK by CPP32 (caspase3). effects of autophosphorylationon activity. J. Biol. Chem. 273, 28733-28739.
Wang J, Chun HJ, Wong W, Spencer DM and Lenardo MJ.(2001). Caspase-10 is an initiator caspase in death receptor signaling. Proc. Natl. Acad. Sci. USA 98, 13884-13888.
Wang XY, Kaneko Y, Repasky E and Subjeck JR.(2000). Heat shock proteins and cancer immunotherapy. Immunol. Invest. 29, 131-137.
Wick G, Perschinka H and Millonig G.(2001). Atherosclerosis as an autoimmune disease: an update. Trends Immunol. 22, 665-9.
Widmann C, Gerwins P, Johnson NL, Jarpe MB and Johnson GL.(1998). MEK kinase 1, a substrate for DEVD-directed caspases, is involved in genotoxin induced apoptosis. Mol. Cell. Biol. 18, 2416-2429.
Wilson R, Goyal L, Ditzel M, Zachariou A, Baker DA, Agapite J, Steller H and Meier P. (2002). The DIAP1 RING finger mediates ubiquitination of Dronc and is indispensable for regulating apoptosis. Nat. Cell Biol. 4, 445-450.
Woltering EJ, van der Bent A and Hoeberichts FA.(2002). Do plant caspases exist? Plant Physiol. 130, 1764-1769.
Workman P.(2004). Combinatorial attack on multistep oncogenesis by inhibiting the Hsp90 molecular chaperone. Cancer Lett. 4, 149-157
Wu JW, Cocina AE, Chai J, Hay BA and Shi Y. (2001). Structural analysis of a functional DIAP1 fragment bound to grim and hid peptides. Mol. Cell 8, 5-104.
Wu W, Misra RS, Russell JQ, Flavell RA, Rincon M and Budd RC.(2006).
Proteolytic regulation of nuclear factor of activated T(NFAT) c2 cells and NFAT activity by caspase-3. J. Biol. Chem. 281, 10682-10690.
Xanthoudakis S, Roy S, Rasper D, Hennessey T, Aubin Y, Cassady R, Tawa P, Ruel R, Rosen A and Nicholson DW.(1999). Hsp60 accelerates the maturation of pro-caspase-3 by upstream activator proteases during apoptosis. EMBO J. 18, 2049-2056.
Xu G, Cirilli M, Huang Y, Rich RL, Myszka DG and Wu H.(2001). Covalent inhibition revealed by the crystal structure of the caspase-8/p35 complex. Nature 410, 494-497.
Xu D, Li Y, Arcaro M, Lackey M and Bergmann A.(2005). The CARD-carrying caspase Drone is essential for most, but not all, developmental cell death in Drosophila. Development 132, 2125-2134.
Xu YS and Kawasaki H.(2001). Isolation and expression of cathepsin B cDNA in hemocytes during metamorphosis of Bombyx mori. Comp. Biochem. Physiol. B130, 393-399.
Yamin TT, Ayala JM and Miller DK.(1996). Activation of the native 45-kDa precursor form of interleukin-1-converting enzyme. J. Biol. Chem. 271, 13273-13282.
Yan N, Wu JW, Huh JR, Chai J, Li W, Hay BA and Shi Y.(2004). Molecular mechanisms of DrICE inhibition by DIAP1 and removal of inhibition by Reaper, Hid, and Grim. Nat. Struct. Mol. Biol. 11, 420-428.
Yan XX, Najbaner J, Woo CC, Dashtipour K, Ribak CE and Leon M. (2001).
Expression of active caspase-3 in mitotic and postmitotic cells of the rat forebrain. J. Comp. Neurol. 433, 4-22.
Yang X, Chang HY and Baltimore D.(1998). Autoproteolytic activation of pro-caspases by oligomerization. Mol. Cell 1, 319-325.
Yang XM, Hou LJ, Dong DJ, Shao HL, Wang JX and Zhao XF. (2006). Cathepsin B-like proteinase is involved in the decomposition of the adult fat body of Helicoverpa armigera. Arch. Insect Biochem. Physiol. 62,1-10.
Yang XM, Hou LJ, Wang JX, and Zhao XF. (2007). Expression and Function of Cathepsin B-Like Proteinase in Larval Hemocytes of Helicorverpa armigera during Metamorphosis. Arch. Insect Biochem. Physiol. (in press).
Yin VP and Thummel CS. (2005). Mechanisms of steroid-triggered programmed cell death in Drosophila. Semin. Cell Dev. Biol. 16,237-243.
Yokoyama H, Mukae N, Sakahira H, Okawa K, Iwamatsu A and Nagata S. (2000). A novel activation mechanism of caspase-activated DNase from Drosophila melanogaster.J. Biol. Chem. 275,12978-12986.
Yokokura T, Dresnek D, Huseinovic N, Lisi S, Abdelwahid E, Bangs P and White K. (2004). Dissection of DIAP1 functional domains via a mutant replacement strategy. J. Biol. Chem. 279, 52603-52612.
Yuan J, Shaham S, Ledoux S, Ellis HM and Horvitz HR. (1993). The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell 75, 641-652.
Zakeri Z and Lockshin RA. (2002). Cell death during development. J. Immunol. Methods 265, 3-20.
Zandy AJ, Lakhani S, Zheng T, Flavell RA and Bassnett S. (2005). Role of the executioner caspases during lens development. J. Biol Chem. 280,30263-30272.
Zhao C and Wang E. (2004). Heat shock protein 90 suppresses tumor necrosis factor alpha induced apoptosis by preventing the cleavage of Bid in NIH3T3 fibroblasts. Cell Signal 16,313-321.
Zhao XF, Wang JX and Wang YC. (1998). Purification and characterization of a cysteine proteinase from eggs of the cotton boll worm, Helicoverpa armigera. Insect Biochem. Mol. Biol.. 28, 259-264.
Zhao XF, Wang JX, Xu XL, Schmid R. and Wiecxorek H. (2002). Molecular cloning and characterization of cathepsin B-like proteinase from the cotton boll worm Helicoverpa armigera. Insect Mol. Biol. 11,567-575.
Zhou L, Schnitzler A, Agapite J, Schwartz LM, Steller H and Nambu JR.(1997).
Cooperative functions of the reaper and head involution defective genes in the programmed cell death of Drosophila central nervous system midline cells. Proc. Natl. Acad. Sci. 94, 5131-5136.
Zhou Q, Krebs JF, Snipas SJ, Price A, Alnemri ES, Tomaselli KJ and Salvesen GS. (1998). Interaction of the baculovirus anti-apoptotic protein p35 with caspases. Specificity, kinetics, and characterization of the caspase/p35 complex. Biochemistry 37, 10757-10765.
Zugel U, Sponaas AM, Neckermann J, Schoel B and Kaufmann SH.(2001). gp96-peptide vaccination of mice against intracellular bacteria. Infect Immun. 69, 4164-4167.
康翠洁。中国对虾先天免疫相关基因克隆与表达研究。山东大学博士论文。2004。
Abraham EG, Islam S, Srinivasan P, Ghosh AK, Valenzuela JG, Ribeiro JM, Kafatos FC, Dimopoulos G and Jacobs-Lorena M.(2004). Analysis of the Plasmodium and Anopheles transcriptional repertoire during ookinete development and midgut invasion. J. Biol. Chem. 279, 5573-5580.
Acehan D, Jiang X, Morgan DG, Heuser JE, Wang X and Akey CW.(2002).Three-dimensional structure of the apoptosome, implications for assembly,procaspase-9 binding, and activation. Mol.Cell. 9, 423-432.
Adachia T, Tomita M and Yoshizatoa K.(2005). Synthesis of prolyl 4-hydroxylase a subunit and type Ⅳ collagen in hemocytic granular cells of silkworm, Bombyx mori: Involvement of type Ⅳ collagen in self-defense reaction and metamorphosis. Matrix Biol. 24, 136-154.
Adams C and Rinne RW.(1982). Stress protein formation: gene expression and environmental interaction with evolutionary significance. Int. Rev. Cytol, 79, 305-315.
Abroad M, Srinivasula SM, Wang L, Litwack G, Fernandes-Alnemri T and Alnemri ES.(1997). Spodoptera frugiperda Caspase-1, a novel insect death protease that cleaves the nuclear immunophilin FKBP46, is the target of the baculovirus antiapoptotic protein p35. J. Bio. Chem. 272, 1421-1424.
Aldo N P, James R W and Walton W D.(1999). Sequence features and phylogenetic analysis of the stress protein Hsp90a in Chinook Salmon (Oncorhynchus tshaw-ytscha), a poikilothermic vertebrate. Biochem. Biophysical Res. Commun. 258, 784-791.
Arama E, Agapite J and Steller H.(2003). Caspase activity and a specific cytochrome C are required for sperm differentiation in Drosophila. Dev. Cell 4, 687-697.
Aravind L, Dixit VM and Koonin EV.(1999). The domains of death, evolution of apoptosis machinery. Trends Biochem. Sci. 24, 47-53.
Aravind L and Koonin E.(2002). Classification of the caspase-hemogiobinase fold, detection of new families and implications for the origin of the eukaryotic separins. Proteins 46, 355-367.
Arbeitman MN, Furlong EE, Imam F, Johnson E, Null BH, Baker BS, Krasnow MA, Scott MP, Davis RW and White KP.(2002). Gene expression during the lifecycle of Drosophila melanogaster. Science 297, 2270-2275.
Asea A, Kraefl SK, Kurt-Jones EA, Stevenson MA, Chen LB, Finberg RW, Koo GC and Calderwood SK.(2000). HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat. Med. 6, 435-442.
Ashhab Y, Alian A, Polliack A, Panet A and Yehuda DB.(2001). Two splicing variants of a new inhibitor of apoptosis gene with different biological properties and tissue distribution pattern. FEBS Lett. 495, 56-60.
Ashkenazi A and Dixit VM.(1998). Death receptors, signaling and modulation. Science 281, 1305-1308.
Baehrecke EH.(2002). How death shapes life during development. Nat. Rev. Mol. Cell. Biol. 3, 779-787.
Beere HM, Wolf BB, Cain K, Mosser DD, Mahboubi A, Kuwana T, Tailor P, Morimoto RI and Cohen GM, Green DR.(2000). Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat. Cell Biol. 2, 469-475.
Bergeron L, Perez GI, Macdonald G, Shi L, Sun Y, Jurisicova A Varmuza S, Latham KE, Flaws JA, Salter JC, Hara H, Moskowitz MA, Li E, Greenberg A, Tilly JL and Yuan J.(1998). Defects in regulation of apoptosis in caspase-2-deficient mice. Genes Dee. 12, 1304-1314.
Bertin J and DiStefano PS.(2000). The PYRIN domain, a novel motif found in apoptosis and inflammation proteins. Cell Death Differ. 7, 1273-1274.
Bideshi DK, Tan Y, Bigot Y and Federici BA.(2005). A viral caspase contributes to modified apoptosis for virus transmission. Genes & Dev. 19, 1416-1421.
Bijian K and Cybulsky AV. (2005). Stress proteins in glomerular epithelial cell injury. Contrib. Nephrol 148, 8-20.
Blanchard F, Rusiniak ME, Sharma K, Sun X, Todorov I, Castellano MM, Gutierrez C, Baumann H and Burhans WC. (2002). Targeted destruction of DNA replication protein Cdc6 by cell death pathways in mammals and yeast. Mol. Biol Cell. 13, 1536-1549.
Boatright KM and Salvesen GS. (2003). Mechanisms of caspase activation. Curr. Opin. Cell Biol. 15,725-731.
Boatright, KM, Renatus M, Scott FL, Sperandio S, Shin H, Pedersen IM, Ricci JE, Edris WA, Sutherlin DP, Green DR and Salvesen GS. (2003). A unified model for apical caspase activation. Mol. Cell. 11, 529-541.
Brancolini C, Lazarevic D, Rodriguez J and Schneider C. (1997). Dismantling cell-cell contacts during apoptosis is coupled to a caspase- dependent proteolytic cleavage of beta-catenin. J. Cell Biol 139, 759-771.
Brancolini C, Sgorbissa A and Schneider C. (1998). Proteolytic processing of the adherens junctions components beta- catenin andgamma-catenin/plakoglobin during apoptosis. Cell Death Differ. 5,1042-1050.
Brockstedt E, Rickers A, Kostka S, Laubersheimer A, Dorken B, Wittmann-Liebold B, Bommert K and Otto A. (1998). Identification of apoptosis-associated proteins in a human Burkitt lymphoma cell line. J. Biol. Chem. 273, 28057-28064.
Browne SJ, MacFarlane M, Cohen GM and Paraskeva C. (1998). The adenomatous polyposis coli protein and retinoblastoma protein are cleaved early in apoptosisand are potential substrates for caspases. Cell Death Differ. 5, 206-213.
Budihardjo I, Oliver H, Lutter M, Luo, X and Wang X. (1999). Biochemical pathways of caspase activation during apoptosis. Annu. Rev. Cell Dev. Biol. 15, 269-290.
Bump NJ, Hackett M, Hugunin M, Seshagiri S, Brady K, Chen P, Ferenz C, Franklin S, Ghayur T and Li P. (1995). Inhibition of ICE family proteases by baculovirus antiapoptotic protein p35. Science 269,1885-1888.
Cakouros D, Daish TJ, Martin D, Baehrecke EH and Kumar S.(2002).Ecdysone-induced expression of the caspase DRONC during hormone-dependent programmed cell death in Drosophila is regulated by Broad-Complex. J. Cell Biol. 157, 985-995.
Cakouros D, Daish TJ and Kumar S.(2004). Ecdysone receptor directly binds the promoter of the Drosophila caspase dronc regulating its expression in specific tissues. J. Cell. Biol. 165, 631-640.
Casciola-Rosen L, Nicholson DW, Chong T, Rowan KR, Thomberry NA, Miller DK and Rosen A.(1996). Apopain/CPP32 cleaves proteins that are essential for cellular repair, a fundamental principle of apoptotic death. J. Exp. Med. 183, 1957-1964.
Cassens U, Lewinski G, Samraj AK, yon Bernuth H, Baust H, Khazaie K and Los M. (2003). Viral modulation of cell death by inhibition of caspases. Arch. Immunol. Ther. Exp. 51, 19-27.
Catherine T, Florence D and Annie B.(2000). Molecular cloning, organellar targeting and developmental expression of mitochondrial chaperone HSP60 in Toxoplasma gondii. Mol. Biochem. Parasitology111, 319-332.
Cerretti DP, Kozlosky CJ, Mosley B, Nelson N, Van Ness K, Greenstreet TA, March CJ, Kronheim SR, Druck T and Cannizzaro LA.(1992) Molecular cloning of the interleukin-1 beta converting enzyme. Science 256, 97-100.
Chai J, Du C, Wu JW, Kyin S, Wang X, and Shi Y.(2000). Structural and biochemical basis of apoptotic activation by Smac/DIABLO. Nature 406, 855-862.
Chai J, WuQ, Shiozaki E, Srinivasula SM, Alnemri ES and Shi Y.(2001a). Crystal structure of a procaspase-7 zymogen: mechanisms of activation and substrate binding. Cell 107, 399-407.
Chai J, Shiozaki E, Srinivasula SM, Wu Q, Datta P, Alnemri ES and Shi Y.(2001b). Structural basis of caspase-7 inhibition by XIAP. Cell 104, 769-780.
Chai, J., Yan, N., Huh, J. R., Wu, J. -W., Li, W., Hay, B. A., and Shi, Y.(2003). Molecular mechanism of Reaper/Grim/Hid-mediated suppression of DIAP1dependent Dronc ubiquitination. Nat. Struct. Biol. 10, 892-898.
Chang DW, Xing Z, Capacio VL, Peter ME and Yang X.(2003). Interdimer processing mechanism of procaspase-8 activation. EMBO J. 22, 4132-4142.
Charette SJ and Landry J.(2000). The interaction of HSP27 with Daxx identifies a potential regulatory role of HSP27 in Fas-induced apoptosis. Ann. N Y Acad. Sci. 926, 126-131.
Chau BN, Borges HL, Chen TT, Masselli A, Hunton IC and Wang JY.(2002). Signal-dependent protection from apoptosis in mice expressing caspase-resistant Rb. Nat. Cell Biol. 4, 757-765.
Chen P, Rodriguez A, Erskine R, Thach T and Abrams JM.(1998). Dredd, a novel effector of the apoptosis activators reaper, grim, and hid in Drosophila. Dev. Biol. 201, 202-216
Chun HJ, Zheng L, Ahmad M, Wang J, Speirs CK, Siegel RM, Dale JK, Puck J, Davis J, Hall CG, Skoda-Smith S, Atkinson TP, Straus SE, and Lenardo MJ.(2002). Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. Nature 419, 395-399.
Cohen GM.(1999). Caspases: the executioners of apoptosis. Biochem. J. 326, 1-16.
Compton MM.(1992). A biochemical hallmark of apoptosis: intemucleosomal degradation of the genome. Cancer Metastasis Rev. 11, 105-19.
Cory S and Adams JM.(2002). The Bcl2 family, Regulators of the cellular life-or-death switch. Nat. Rev. Cancer 2, 647-656.
Crook NE, Clem RJ and Miller LK.(1993). An apoptosis-inhibiting baculovirus gene with a zinc finger-like motif. J. Virol. 67, 2168-2174.
Cryns VL, Byun Y, Rana A, Mellor H, Lustig KD, Ghanem L, Parker PJ, Kirschner MW and Yuan J.(1997). Specific proteolysis of the kinase protein kinase C related kinase 2 by caspase-3 during apoptosis: identification by a novel, small pool expression cloning strategy. J. Biol. Chem. 272, 29449-29453.
Datta R, Kojima H, Yoshida K and Kufe D.(1997). Caspase-3-mediated cleavage of protein kinase C theta in induction of apoptosis. J. Biol. Chem. 272, 20317-20320.
De Botton S, Sabri S, Daugas E, Zermati Y, Guidotti JE, Hermine O, Kroemer G, Vainchenker W and Debili N. (2002). Platelet formation is the consequence of caspase activation within megakaryocytes. Blood 100,1310-1317.
De Jong L, Moreau X, Jean S, Scher O and Thiery A. (2006). Expression of the heat shock protein Hsp70 in chloride target cells of mayfly larvae from motorway retention pond: A biomarker of osmotic shock. Sci. Total Environ. 366,164-173.
DeNagel DC and Pierce SK. (1993). Heat shock proteins in immune responses. Crit. Rev. Immunol 13, 71-81.
Degterev A, Boyce M and Yuan J. (2003). A decade of caspases. Oncogene 22, 8543-8567.
Deveraux QL and Reed JC. (1999). IAP family proteins, suppressors of apoptosis. Genes Dev. 13,239-252.
Dhadialla TS, Carlson GR and Le DP. (1998). New insecticides with ecdysteroidal and juvenile hormone activity. Annu. Rev. Entomol. 43, 545-569.
Donepudi M, Mac Sweeney A, Briand C and Grutter MG. (2003). Insights into the regulatory mechanism for caspase - 8 activation. Mol. Cell 11, 543 -549.
Dorstyn L, Colussi PA, Quinn LM, Richardson H and Kumar S. (1999). DRONC, an ecdysone inducible Drosophila caspase. Proc. Natl. Acad. Sci. USA 96,4307-4312.
Dorstyn L, Colussi PA, Quinn LM, Richardson H and Kumar S. (1999). DRONC, an ecdysone-inducible Drosophila caspase. Proc.Natl Acad. Sci. 13, 4307-4312.
Dorstyn L and Kumar S. (2006). A cytochrome c-free fly apoptosome. Cell Death Differ. 13,1049-1051.
Doumanis J, Quinn L, Richardson H and Kumar S. (2001). STRICA, a novel Drosophila caspase with an unusual serine/threonine-rich prodomain, interacts with DIAP1 and DIAP2. Cell Death Differ. 8,387-394.
Du C, Fang M, Li Y and Wang X. (2000). Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation during apoptosis. Cell 102, 33-42.
Dunlap DY and Matsumura F. (1997). Development of broad spectrum antibodies to heat shock protein 70s as biomarkers for detection of multiple stress by pollutants and environmental factors. Ecotoxicol Environ. Saf. 37, 238-244.
Earnshaw WC, Martins LM and Kaufmann SH. (1999). Mammalian caspases: Structure, activation, substrates, and functions during apoptosis. Annu. Rev. Biochem. 68,383-424.
Eckhart L, Ballaun C, Uthman A, Kittel C, Stichenwirth M, Buchberger M, Fischer H, Sipos W, and Tschachler E (2005). Identification and characterization of a novel mammalian caspase with proapoptotic activity. J.Bio.Chem. 280, 35077-35080.
Ellis RE, Yuan JY and Horvitz HR. (1991). Mechanisms and functions of cell death. Annu. Rev. Cell. Biol. 7,663-698.
Fernandes-Alnemri T, Litwack G and Alnemri ES. (1994). CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1P-converting Enzyme. J.Biol.Chem. 269,49-53.
Fernandes-Alnemri T, Armstrong R and Krebs J. (1996). In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains. Proc. Natl. Acad. Sci. USA 93, 7464-7469.
Fernando P, Kelly JF, Balazsi K, Slack RS and Megeney LA. (2002). Caspase 3 activity is required for skeletal muscle differentiation. Proc. Natl. Acad. Sci. USA 99, 11025-11030.
Fesik SW and Shi Y. (2001). Controlling caspases. Science 294,1477-1478.
Fischer U, Janicke RU and Schulze-Osthoff K. (2003). Many cuts to ruin, a comprehensive update of caspase substrates. Cell Death Differ. 10,76-100.
Fraser AG and Evan GI. (1997). Identification of a Drosophila melanogaster ICE/CED-3- related protease, drICE. EMBO J 16,2805-2813.
Fraser AG, McCarthy NJ and Evan GI. (1997). drICE is an essential caspase required for apoptotic activity in Drosophila cells. EMBO J. 16, 6192-6199.
Frost V, Delikat S, Al-Mehairi S and Sinclair AJ.(2001). Regulation of p27KIP1 in Epstein-Barr virus immortalized lymphoblastoid cell lines involves non-apoptotic caspase cleavage. J. Gen. Virol. 82, 3057-3066.
Frutos S, Moscat J and Diaz-Meco MT.(1999). Cleavage of zetaPKC but not lambda/iotaPKC by caspase-3 during UV-induced apoptosis. J. Biol. Chem. 274, 10765-10770.
Geisbrecht ER and Montell DJ.(2004). A role for Drosophila IAP1-mediated caspase inhibition in Rac-dependent cell migration. Cell 118, 111-125.
Germain M, Affar EB, D'Amours D, Dixit VM, Salvesen GS and Poirier GG.(1999).
Cleavage of automodified Poly(ADP-ribose) polymerase during apoptosis. Evidence for involvement of caspase-7. J. Biol. Chem. 274, 28379-28384.
Golks A, Brenner D, Fritsch C, Krammer PH and Lavrik IN.(2005). C-FLIPR, a new regulator of death receptor-induced apoptosis. J. Biol. Chem. 280, 14507-14513.
Gordon SA, Hoffman RA, Simmons RL and Ford HR.(1997). Induction of heat shock protein 70 protects thymocytes against radiation-induced apoptosis. Arch. Surg. 132, 1277-1282.
Gueth-Hallonet C, Weber K and Osborn M.(1997). Cleavage of the nuclear matrix protein NuMA during apoptosis. Exp. Cell. Res. 233, 21-24.
Hakem R, Hakem A, Duncan GS, Henderson JT, Woo M, Soengas MS Elia A, de la Pompa JL, Kagi D, Khoo W, Potter J, Yoshida R, Kaufman SA, Lowe SW, Penninger JM and Mak TW. (1998). Differential requirement for caspase-9 in apoptotic pathways in vivo. Cell 94, 339-352.
Harris JL, Backes BJ, Leonetti F, Mahrus S, Ellman JA and Craik CS. (2000). Rapid and general profiling of protease specificity by using combinatorial fluorogenic substrate libraries. Proc. Natl. Acad. Sci. USA 97, 7754-7759.
Hartl FU.(1996). Molecular chaperones in cellular protein folding. Nature 381, 571-579.
Harvey NL, Daish T, Mills K, Dorstyn L, Quinn LM, Read SH, Richardson H and Kumar S. (2001). Characterization of the Drosophila caspase, DAMM. J. Biol. Chem. 276, 25342-25350.
Hatsugai N, Kuroyanagi M, Yamada K, Meshi T, Tsuda S, Kondo M, Nishimura M and Hara-Nishimura I. (2004). A plant vacuolar protease, VPE, mediates virus-induced hypersensitive cell death. Science 305, 855-858.
Hatsugai N, Kuroyanagi M, Nishimura M and Hara-Nishimura I. (2006). A cellular suicide strategy of plants: vacuole-mediated cell death. Apoptosis 11, 905-911.
Hawkins CJ, Wang SL and Hay BA. (1999). A cloning method to identify caspases and their regulators in yeast, identification of Drosophila IAPl as an inhibitor of the Drosophila caspase DCP-1.Proc. Natl. Acad. Sci. USA 96, 2885-2890.
Hawkins CJ, Yoo SJ, Peterson EP, Wang SL, Vernooy SY and Hay BA. (2000). The Drosophila caspase DRONC is a glutamate/aspartate protease whose activity is regulated by DIAP1, HID and GRIM. J. Biol. Chem. 275, 27084-27093.
Hay BA, Wassarman DA and Rubin GM. (1995). Drosophila homologs of baculovirus inhibitor of apoptosis proteins function to block cell death. Cell 83, 1253-1262.
Hays R, Wickline L and Cagan R. (2002). Morgue mediates apoptosis in the Drosophila melanogaster retina by promoting degradation of DIAP1. Nat.Cell Biol. 4, 425-431.
Heifer B, Boswell BC, Finlay D, Cipres A, Vuori K, Bong Kang T, Wallach D, Dorfleutner A, Lahti JM, Flynn DC and Frisch SM. (2006). Caspase-8 promotes cell motility and calpain activity under nonapoptotic conditions. Cancer Res. 66, 4273-4278.
Herrmann M, Lorenz HM, Voll R, Grunke M, Woith W and Kalden JR. (1994). A Rapid and simple method for the isolation of apoptotic DNA fragments. Nucleic. Acid Res. 22, 5506-5507.
Horvitz HR. (2003). Worms, life, and death. Chembiochem. 4, 697-711.
Hsu HL and Yeh NH. (1996). Dynamic changes of NuMA during the cell cycle and possible appearance of a truncated form of NuMA during apoptosis. J.Cell. Sci. 109, 277-288.
Hu S and Yang X. (2000). dFADD, a novel death domain-containing adapter protein for the Drosophila caspase DREDD. J. Biol. Chem. 275, 30761-30764.
Huang Y, Park YC, Rich RL, Segal D, Myszka DG and Wu H. (2001). Structural basis of caspase inhibition by XIAP, differential roles of the Linker versus the BIR domain. Cell 104, 781-790.
Huh JR, Guo M and Hay BA. (2004). Compensatory proliferation induced by cell death in the Drosophila wing disc requires activity of the apical cell death caspase Dronc in a nonapoptotic role. Curr. Biol. 14,1262-1266.
Inohara N, Koseki T, Hu Y, Chen S and Nunez G. (1997). CLARP, a death effector domain containing protein interacts with caspase-8 and regulates apoptosis. Proc. Natl. Acad. Sci. USA 94,10717-10722.
Jiang C, Lamblin AF, Steller H and Thummel CS. (2000). A steroid-triggered transcriptional hierarchy controls salivary gland cell death during Drosophila metamorphosis. Mol. Cell 5,445-55.
Jiang X and Wang X. (2000). Cytochrome c promotes caspase-9 activation by inducing nucleotide binding to Apaf-1. J. Biol. Chem. 275,31199-31203.
Kang TB, Ben-Moshe T, Varfolomeev EE, Pewzner-Jung Y, Yogev N, Jurewicz A, Waisman A, Brenner O, Haffner R, Gustafsson E, Ramakrishnan P, Lapidot Tand Wallach D. (2004). Caspase-8 serves both apoptotic and nonapoptotic roles. J. Immunol. 173, 2976-2984.
Kasof GM and Gomes BC. (2001). Livin, a novel inhibitor of apoptosis protein family member. J. Biol. Chem. 276,3238-3246.
Kato D, Boatright KM, Berger AB, Nazif T, Blum G, Ryan C Chehade KA, Salvesen GS and Bogyo M. (2005). Activity-based probes that target diverse cysteine protease families. Nature Chem. Biol. 1, 33-38.
Kanuka H, Sawamoto K, Inohara N, Matsuno K, Okano H and Miura M.(1999).Control of the cell death pathway by Dapaf-1, a Drosophila Apaf-1/CED-4-related caspase activator. Mol. Cell 4, 757-769.
Khwaja A and Tatton L.(1999). Caspase-mediated proteolysis and activation of protein kinase Cdelta plays a central role in neutrophil apoptosis. Blood 94, 291-301.
Kilpatrick ZE, Cakouros D and Kumar S.(2005). Ecdysone-mediated up-regulation of the erector caspase DRICE is required for hormone-dependent apoptosis in Drosophila cells. J. Biol. Chem. 280, 11981-11986.
Kim YM, de Vera ME, Watkins SC and Billiar TR.(1997). Nitric oxide protects cultured rat hepatocytes from tumor necrosis factor-alpha-induced apoptosis by inducing heat shock protein 70 expression. J. Biol. Chem. 272, 1402-1411.
Kischkel FC, Hellbardt S, Behrmann I, Germer M, Pawlita M, Krammer PH and Peter ME. (1995). Cytotoxicity-dependent APO-1(Fas/CD95)-associated proteins form a death-inducing signaling complex(DISC) with the receptor. EMBO J. 14, 5579-5588.
Kischkel FC, Lawrence DA, Tinel A, LeBlanc H, Virmani A, Schow P, Gazdar A, Blenis J, Amott D and Ashkenazi A.(2001). Death receptor recruitment of endogenous caspase-10 and apoptosis initiation in the absence of caspase-8. J. Biol. Chem. 276, 46639-46646.
Kita T.(2000). The role of heat shock proteins on the disordered tissues: implication for the pathogenesis and diagnostics in the forensic practice, Nippon Hoigaku Zasshi 54, 367-371.
Kobayashi K, Inohara N, Hemandez LD, Galan JE, Nunez G, Janeway CA, Medzhitov R and Flavell RA.(2002). RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems. Nature 416, 194-199.
Ko"hler H R, Belitz B, Eckwert H, Adam R, Rahman B and Tronteli P. Validation of Hsp70 stress gene expression as a marker of metal effects in Deroceras reticulatum (Pulmonata): correlation with demographic parameters. Environ. Toxicol. Chem. 17, 2246-2253.
Kondo S, Senoo-Matsuda N, Hiromi Y and Miura M.(2006). DRONC coordinates cell death and compensatory proliferation. Mol. Cell Biol. 26,7258-7268.
Korsmeyer SJ, Wei MC, Saito M, Weiler S, Oh KJ and Schlesinger PH. (2000). Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c. Cell Death Differ. 7,1166-1173.
Kothakota S, Azuma T, Reinhard C, Klippel A, Tang J, Chu K, McGarry TJ, Kirschner MW, Koths K, Kwiatkowski DJ and Williams LT. (1997). Caspase-3-generated fragment of gelsolin, effector of morphological change in apoptosis. Science 278,294-298.
Krueger A, Schmitz I, Baumann S, Krammer PH and Kirchhoff S. (2001). Cellular flice-inhibitory protein splice variants inhibit different steps of caspase-8 activation at the cd95 death-inducing signaling complex. J. Biol Chem. 276, 20633-20640.
Kuida K, Zheng TS, Na S, Kuan C, Yang D, Karasuyama H, Rakic P and Flavell RA.(1996). Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice. Nature 384,368-372.
Kuida K, Haydar TF, Kuan C-Y, Gu Y, Taya C, Karasuyama H Su MS, Rakic P and Flavell RA. (1998). Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9. Cell 94,325-337.
Kumar S and Doumanis J. (2000). The fly caspases. Cell Death Differ. 7,1039-1044.
Kumar S and Cakouros D. (2004). Transcriptional control of the core cell-death machinery. Trends Biochem. Sci. 29,193-199.
LaCount DJ, Hanson SF, Schneider CL and Friesen PD. (2000). Caspase inhibitor P35 and inhibitor of apoptosis Op-IAP block in vivo proteolytic activation of an effector caspase at different steps. J. Biol. Chem. 275,15657 -15664.
Laemmli UK. (1970). Cleavage of structural proteins during the assemble of the head of bacteriophage T4. Nature 227, 680-685.
Lakhani SA, Masud A, Kuida K, Porter Jr GA, Booth CJ, Mehal WZ, Inayat I and Flavell RA. (2006). Caspases 3 and 7, key mediators of mitochondrial events of apoptosis. Science 311, 847-851.
Lamkanfi M, D'Hondt K, Vande Walle L, Van Gurp M, Denecker G, Demeulemcester J, Kalai M, Declercq W, Saelens X and Vandenabeele P.(2005). Anovel caspase-2 complex containing TRAF2 and RIP1. J. Biol. Chem. 280, 6923-6932.
Lamkanfi M, Festjens N, Declercq W, Vanden Berghe T and Vandenabeele P.(2007). Caspases in cell survival, proliferation and differentiation. Cell Death Differ. 14, 44-55.
Lavrik I, Krueger A, Schmitz I, Baumann S, Weyd H, Krammer PH and Kirchhoff S. (2003). The active caspase-8 heterotetramer is formed at the CD95 DISC. Cell Death Differ. 10, 144-145.
Lavrik IN, Golks A, and Krammer PH.(2005). Caspases, pharmacological manipulation of cell death. J. Clin. Invest. 115, 2665-2672.
Lee CY, Cooksey BA and Baehrecke EH.(2002). Steroid regulation of midgut cell death during Drosophila development. Dev. Biol. 250, 101-111.
Leulier F, Rodriguez A, Khush RS, Abrams JM and Lemaitre B.(2000). The Drosophila caspase Dredd is required to resist gram-negative bacterial infection. EMBO Rep 1, 353-358.
Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES and Wang X. (1997). Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91, 479-489.
Lockshin RA and Zakeri Z.(2001). Programmed cell death and apoptosis: origins of the theory. Nat. Rev. Mol. Cell, Biol. 2, 545-550.
Mahroof R, Zhu KY, Neven L, Subramanyam B and Bai J.(2005). Expression patterns of three heat shock protein 70 genes among developmental stages of the red flour beetle, Tribolium castaneum(Coleoptera: Tenebrionidae). Comp. Biochem. Physiol. 141, 247-256.
Martin J and Hartl FU.(1997). Chaperone assisted protein folding. Curr. Opinion in Struct. Biol., 7, 41-52.
Martin SJ, Amarante-Mendes GP, Shi L, Chuang TH, Casiano CA, O'Brien GA, Fitzgerald P, Tan EM, Bokoch GM, Greenberg AH, and Green DR. (1996). The cytotoxic cell protease granzyme B initiates apoptosis in a cell-free system by proteolytic processing and activation of the ICE/CED-3 family protease, CPP32, via a novel two-step mechanism. EMBO J. 15,2407-2416.
Martin DA, Siegel RM, Zheng L and Lenardo MJ. (1998). Membrane oligomerization and cleavage activates the caspase-8 (FLICE/MACHalpha1) death signal. J. Biol. Chem. 273, 4345-4349.
Martinon F and Tschopp J. (2004). Inflammatory caspases, linking an intracellular innate immune system to autoinflammatory diseases. Cell. 117, 561-574.
Meier P, Silke J, Leevers SJ and Evan GI. (2000). The Drosophila caspase DRONC is regulated by DIAPI. EMBO J. 19,598- 611.
Micheau O, Thome M, Schneider P, Holler N, Tschopp J, Nicholson DW, Briand C and Grutter MG. (2002). The long form of FLIP is an activator of caspase-8 at the Fas death-inducing signaling complex. J. Biol. Chem. 277, 45162-45171.
Milhas D, Cuvillier O, Therville N, Clave P, Thomsen M, Levade T Benoist H and Segui B. (2005). Caspase-10 triggers Bid cleavage and caspase cascade activation in FasL-induced apoptosis. J. Biol. Chem. 280,19836-19842.
Mills K, Daish T and Kumar S. (2005). The function of the Drosophila caspase DRONC in cell death and development. Cell Cycle 4, 744-746.
Mills K, Daish T, Harvey KF, Pfleger CM, Hariharan IK and Kumar S. (2006). The Drosophila melanogaster Apaf-1 homologue ARK is required for most, but not all, programmed cell death. J. Cell Biol. 172, 809-815.
Miura M, Chen XD, Allen MR, Bi Y, Gronthos S, Seo BM, Lakhani S, Flavell RA, Feng XH, Robey PG, Young M and Shi S. (2004). A crucial role of caspase-3 in osteogenic differentiation of bone marrow stromal stem cells. J. Clin. Invest. 114, 1704-1713.
Moseley PL. (1997). Heat shock proteins and heat adaptation of the whole organism. J. Applied Physiol. 83,1413-1 417.
Mosser DD, Caron AW, Bourget L, Meriin AB, Sherman MY, Morimoto RI and Massie B. (2000). The chaperone function of Hsp70 is required for protection against stress-induced apoptosis. Mol Cell Biol 20,7146-7159.
Muller F, Adori C and Sass M. (2004). Autophagic and apoptotic features during programmed cell death in the fat body of the tobacco hornworm (Manduca sexta). Eur. J. Cell Biol 83, 67-78.
Multhoff G (2006). Heat shock proteins in immunity. Handb. Exp. Pharmacol 172, 279-304.
Muro I, Berry DL, Huh JR, Chen CH, Huang H, Yoo SJ, Guo M, Baehrecke EH and Hay BA. (2006). The Drosophila caspase Ice is important for many apoptotic cell deaths and for spermatid individualization, a nonapoptotic process. Development 133, 3305-3315.
Muzio M, Stockwell BR, Stennicke HR, Salvesen GS and Dixit VM. (1998). An Induced proximity model for caspase-8 activation. J.Bio.Chem. 273, 2926-2930.
Nicholson DW. (1999). Caspase structure, proteolytic substrates, and function during apoptotic cell death. Cell Death Differ. 6,1028-1042.
Parthasarathy R and Palli SR. (2007). Developmental and hormonal regulation of midgut remodeling in a lepidopteran insect, Heliothis virescens. Mech. Dev. 124, 23-34.
Pei Z, Reske G, Huang Q, Hammock BD, Qi Y and Chejanovsky N. (2002). Characterization of the apoptosis suppressor protein P49 from the Spodoptera littoralis nucleopolyhedrovirus. J. Biol. Chem. 277, 677-684.
Petrilli V, Herceg Z, Hassa PO, Patel NS, Di Paola R, Cortes U, Dugo L, Filipe HM, Thiemermann C, Hottiger MO, Cuzzocrea S, and Wang ZQ. (2004). Noncleavable poly(ADP-ribose) polymerase-1 regulates the inflammation response in mice. J. Clin. Invest. 114,1072-1081.
Plowman JE, Bryson WG and Jordan TW. (2000). Application of proteomics for determining protein markers for wool quality traits. Electrophoresis 21,1899-1906.
Porter AG and Janicke RU.(1999). Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 6, 99-104.
Quinn LM, Dorstyn L, Mills K, Colussi PA, Chen P, Coombe M, Abrams J, Kumar S and Richardson H.(2000). An essentialrole for the caspase Dronc in developmentally programmed cell death in Drosophila. J. Biol. Chem. 275, 40416-40424.
Rao L, Perez D and White E.(1996). Lamin proteolysis facilitates nuclear events during apoptosis. J. Cell. Biol. 135, 1441-1455.
Riddiford LY, Hiruma K, Zhou X and Nelson CA.(2003). Insights into the molecular basis of the hormonal control of molting and metamorphosis from Manduca sexta and Drosophila melanogaster. Insect Biochem. Mol. Bio. 33, 1327-1338.
Riedl SJ, Renatus M, Schwarzenbacher R, Zhou Q, Sun C, Fesik SW, Liddington RC and Salvesen GS.(2001b). Structural basis for the inhibition of caspase-3 by XIAP. Cell 104, 791-800.
Rinehart JP, YocumGD and Denlinger DL.(2000). Developmental upregulation of inducible hsp70 transcripts, but not the cognate form, during pupal diapause in the flesh fly, Sarcophaga crassipalpis. Insect Biochem. Mol. Biol. 30, 515-521.
Rinehart JP, Hayward SAL, Elnitsky MA, Sandro LH, Lee RE and Denlinger DL. (2006). Continuous up-regulation of heat shock proteins in larvae, but not adults, of a polar insect. Proc. Natl. Acad. Sci. USA 103, 14223-14227.
Ritossa FM.(1962). A new puffing pattern induced by heat shock and DNP in Drosophilia. Experientia, 18, 571-573.
Rodriguez A, Oliver H, Zou H, Chen P, Wang X and Abrams JM.(1999). Dark is a Drosophila homologue of Apaf-1/CED-4 and functions in an evolutionarily conserved death pathway. Nat. Cell Biol. 1, 272-279.
Rojo E, Martin R, Carter C, Zouhar J, Pan S, Plotnikova J, Jin H, Paneque M, Sanchez-Serrano JJ, Baker B, Ausubel FM and Raikhel NV.(2004). VPEgamma exhibits a caspase-like activity that contributes to defense against pathogens. Curr. Biol. 14, 1897-1906.
Rotonda J, Nicholson DW, Fazil KM, GallantM, Gareau Y, Labclle M, Pcterson EP, Rasper DM, Rucl R, Vaillancourt JP, Thornbcrry NA and Bcckcr JW. (1996). The three-dimensional structure of apopain/CPP32, a key mediator of apoptosis. Nat. Struct. Biol. 3, 619-625.
Rybczynski R and Gilbert LI.(2000). cDNA cloning and expression of a hormoneregulated heat shock protein(hsc 70) from the prothoracic gland of Manduca sexta. Insect Biochem. Mol. Biol. 30, 579-589.
Sakahira H, Enari M and Nagata S.(1998). Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis. Nature 391, 96-99.
Salch A, Srinivasula SM, Balkir L, Robbins PD and Alncmri ES.(2000). Negative regulation of the Apaf-1 apoptosomc by Hsp70. Nat. Cell Biol. 2, 476-483.
Salmena L, Lemmers B, Hakem A, Matysiak-Zablocki E, Murakami K, Au PY, Berry DM, Tamblyn L, Shehabeldin A, Migon E, Wakeham A, Bouchard D, Yeh WC, McGlade JC, Ohashi PS, and Hakem R.(2003). Essential role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity. Genes Dev. 17, 883-895.
Sambrook J et al., (1989) 《分子克隆》第三版.
Saraste A and Pulkki K.(2000). Morphologic and biochemical hallmarks of apoptosis. Cardiovasc Res. 45, 528-537.
Scaffidi C, Medema JP, Krammer PH and Peter ME.(1997). FLICE is predominantly expressed as two functionally active isoforms, caspase-8/a and caspase-8/b. J. Biol. Chem. 272, 26953-26958.
Scaffidi C, Kischkel FC, Krammer PH and Peter ME. 1999a. Analysis of the CD95 (APO-1/Fas) death-inducing signaling complex(DISC) by high resolution two-dimensional gel electrophoresis. Methods Enzymol. 322, 363-373.
Scaffidi C, Krammer PH and Peter ME.(1999b). Isolation and analysis of components of CD95(APO-1/Fas) death-inducing signaling complex. Methods. 17, 287-291.
Scaffidi C, Schmitz I, Krammer PH and Peter ME.(1999c). The role of c-FLIP in modulation of CD95-induced apoptosis. J. Biol. Chem. 274, 1541-1548.
Schlesinger MJ.(1990). Heat shock proteins. J. Biol. Chem. 265, 12111-12114.
Schwab BL, Leist M, Knippers R and Nicotera P.(1998). Selective proteolysis of the nuclear replication factor MCM3 in apoptosis. Exp. Cell. Res. 238, 415-421.
Shi Y.(2001). A structural view of mitochondria-mediated apoptosis. Nat. Struct. Biol. 8, 394-401.
Shi Y.(2005). Caspase activation, inhibition, and reactivation, A mechanistic view. Protein Science 13, 1979-1987.
Song Q, Lees-Miller SP, Kumar S, Zhang Z, Chan DW, Smith GC, Jackson SP, Alnemri ES, Litwack G, Khanna KK and Lavin MF.(1996). DNA-dependent protein kinase catalytic subunit, a target for an ICE-like protease in apoptosis. EMBO J. 15, 3238-3246.
Song Z, McCall K and Steller H.(1997). DCP-1, a Drosophila cell death protease essential for development. Science 275, 536-540.
Sordet O, Rebe C, Plenchette S, Zermati Y, Hermine O, Valnchenker W, Garrido C, Solar3/E and Dubrez-Daloz L.(2002). Specific involvement of caspases in the differentiation of monocytes into macrophages. Blood 100, 4446-4453.
Sprick MR, Rieser E, Stahl H, Grosse-Wilde A, Weigand MA and Walczak H. (2002). Caspase-10 is recruited to and activated at the native TRAIL and CD95 death-inducing signaling complexes in a FADD-dependent manner but can not functionally substitute caspase-8. EMBO J. 21, 4520-4530
Srinivasula SM, Hegde R, Saleh A, Datta P, Shiozaki E, Chai J, Lee RA, Robbins PD, Fernandes-Alnemri T, Shi Y and Alnemri ES.(2001a). A conserved XIAP interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature 410, 112-116.
Srinivasula SM, Saleh A, Hedge R, Datta P, Shiozaki EJ, Robbins PD, Fernandes-Alnemri T, Shi Y and Alnemri ES. (2001b). A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO mediates opposing effects on caspase activity and apoptosis. Chem. Biol. 7,423-432.
Stennicke HR, Renatus M, Meldal M and Salvesen GS. (2000). Internally quenched fluorescent peptide substrates disclose the subsite preferences of human caspases 1, 3, 6,7 and 8. Biochem J. 350,563-568.
Stennicke HR and Salvesen GS. (1999). Caspases: preparation and characterization. Methods. 17,313-319.
Stennicke HR, Ryan CA and Salvesen GS. (2002). Reprieval from execution, the molecular basis of caspase inhibition. Trends Biochem. Sci. 27, 94-101.
Stoven S, Silverman N, Junell A, Hedengren-Olcott M, Erturk D, Engstrom Y, Maniatis T, and Hultmark D. (2003). Caspase-mediated processing of the Drosophila NF-kappaB factor relish. Proc. Natl. Acad. Sci. USA 100,5991-5996.
Suarez MF, Filonova LH, Smertenko A, Savenkov EI, Clapham DH, von Arnold S, Zhivotovsky B and Bozhkov PV. (2004). Metacaspase-dependent programmed cell death is essential for plant embryogenesis. Curr. Biol. 14, 339-340.
Takahashi A, Alnemri ES, Lazebnik YA, Fernandes-Alnemri T, LitwackG, Moir RD, Goldman RD, Poirier GG, Kaufmann SH and Earnshaw WC. (1996). Cleavage of lamin A by Mch2 alpha but not CPP32, multiple interleukin 1 beta converting enzyme-related proteases with distinct substrate recognition properties are active in apoptosis. Proc. Natl. Acad. Sci. USA 93, 8395-8400.
Tang D and Kidd VJ. (1998). Cleavage of DFF-45/ICAD by multiple caspases is essential for its function during apoptosis. J. Biol. Chem. 273,.28549-28552.
Tartaglia LA, Ayres TM, Wong GH and Goeddel DV. (1993). A novel domain within the 55 kd TNF receptor signals cell death. Cell 74, 845-853.
Tesco G, Kim TW, Diehlmann A, Beyreuther K and Tanzi RE. (1998). Abrogation of the presenilin 1/beta-catenin interaction and preservation of the heterodimeric presenilin 1 complex following caspase activation. J. Biol. Chem. 273, 33909-33914.
Tewari M, Quan LT, O'Rourke K, Desnoyers S, Zeng Z, Beidler DR, Poirier GG, Salvesen GS and Dixit VM. (1995). Yama/CPP32-beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly (ADP-ribose) polymerase. Cell 81, 801-809.
Thornberry NA, Bull HG, Calaycay JR, Chapman KT, Howard AD, Kostura MJ, Miller DK, Molineaux SM, Weidner JR and Aunins J. (1992). A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature 356, 768-774.
Thummel CS. (2001). Steroid-triggered death by autophagy. BioEssays 23, 677-682.
Timmer JC and Salvesen GS. (2007). Caspase substrates. Cell Death and Differ. 14, 66-72.
Tinel A and Tschopp J. (2004). The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress. Science 304,.843-846.
Tissieres A, Mitchell HK and Tracy UM. (1974). Protein synthesis in salivary glands of Drosophila melanogaster: Relation to chromosome puffs. J. Mol. Biol. 85,389-398.
Truman JW and Riddiford LM. (2002). Endocrine insights into the evolution of metamorphosis in insects. Annu. Rev. Entomol. 47, 467-500.
Varfolomeev EE, Schuchmann M, Luria V, Chiannilkulchai N, Beckmann JS, Mett IL Rebrikov D, Brodianski VM, Kemper OC, Kollet O, Lapidot T, Soffer D, Sobe T, Avraham KB, Goncharov T, Holtmann H, Lonai P and Wallach D. (1998). Targeted disruption of the mouse caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally. Immunity 9,267-276.
Varfolomeev EE, Maecker H, Sharp D, Lawrence D, Renz M, Vucic D and Ashkenazi A. (2005). Molecular determinants of kinase pathway activation by Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand. J. Biol. Chem. 280, 40599-40608.
Verhagen AM, Ekert PG, Pakusch M, Silke J, Connolly LM, Reid GE, Moritz RL, Simpson RJ and Vaux DL. (2000). Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing LAP proteins. Cell 102,43-53.
Vucic D, Stennicke HR, Pisabarro MT, Salvesen GS and Dixit VM. (2000). ML-IAP, a novel inhibitor of apoptosis that is preferentially expressed in human melanomas. Curr. Biol. 10, 1359-1366.
Wallin RP, Lundqvist A, More SH, von Bonin A, Kiessling R and Ljunggren HG. (2002). Heat-shock proteins as activators of the innate immune system. Trends Immunol. 23, 130-135.
Walter BN, Huang Z, Jakobi R, Tuazon PT, Alnemri ES, Litwack G and Traugh JA. (1998). Cleavage and activation of p21-activated protein kinase gamma-PAK by CPP32 (caspase3). effects of autophosphorylationon activity. J. Biol. Chem. 273, 28733-28739.
Wang J, Chun HJ, Wong W, Spencer DM and Lenardo MJ.(2001). Caspase-10 is an initiator caspase in death receptor signaling. Proc. Natl. Acad. Sci. USA 98, 13884-13888.
Wang XY, Kaneko Y, Repasky E and Subjeck JR.(2000). Heat shock proteins and cancer immunotherapy. Immunol. Invest. 29, 131-137.
Wick G, Perschinka H and Millonig G.(2001). Atherosclerosis as an autoimmune disease: an update. Trends Immunol. 22, 665-9.
Widmann C, Gerwins P, Johnson NL, Jarpe MB and Johnson GL.(1998). MEK kinase 1, a substrate for DEVD-directed caspases, is involved in genotoxin induced apoptosis. Mol. Cell. Biol. 18, 2416-2429.
Wilson R, Goyal L, Ditzel M, Zachariou A, Baker DA, Agapite J, Steller H and Meier P. (2002). The DIAP1 RING finger mediates ubiquitination of Dronc and is indispensable for regulating apoptosis. Nat. Cell Biol. 4, 445-450.
Woltering EJ, van der Bent A and Hoeberichts FA.(2002). Do plant caspases exist? Plant Physiol. 130, 1764-1769.
Workman P.(2004). Combinatorial attack on multistep oncogenesis by inhibiting the Hsp90 molecular chaperone. Cancer Lett. 4, 149-157
Wu JW, Cocina AE, Chai J, Hay BA and Shi Y. (2001). Structural analysis of a functional DIAP1 fragment bound to grim and hid peptides. Mol. Cell 8, 5-104.
Wu W, Misra RS, Russell JQ, Flavell RA, Rincon M and Budd RC.(2006).
Proteolytic regulation of nuclear factor of activated T(NFAT) c2 cells and NFAT activity by caspase-3. J. Biol. Chem. 281, 10682-10690.
Xanthoudakis S, Roy S, Rasper D, Hennessey T, Aubin Y, Cassady R, Tawa P, Ruel R, Rosen A and Nicholson DW.(1999). Hsp60 accelerates the maturation of pro-caspase-3 by upstream activator proteases during apoptosis. EMBO J. 18, 2049-2056.
Xu G, Cirilli M, Huang Y, Rich RL, Myszka DG and Wu H.(2001). Covalent inhibition revealed by the crystal structure of the caspase-8/p35 complex. Nature 410, 494-497.
Xu D, Li Y, Arcaro M, Lackey M and Bergmann A.(2005). The CARD-carrying caspase Drone is essential for most, but not all, developmental cell death in Drosophila. Development 132, 2125-2134.
Xu YS and Kawasaki H.(2001). Isolation and expression of cathepsin B cDNA in hemocytes during metamorphosis of Bombyx mori. Comp. Biochem. Physiol. B130, 393-399.
Yamin TT, Ayala JM and Miller DK.(1996). Activation of the native 45-kDa precursor form of interleukin-1-converting enzyme. J. Biol. Chem. 271, 13273-13282.
Yan N, Wu JW, Huh JR, Chai J, Li W, Hay BA and Shi Y.(2004). Molecular mechanisms of DrICE inhibition by DIAP1 and removal of inhibition by Reaper, Hid, and Grim. Nat. Struct. Mol. Biol. 11, 420-428.
Yan XX, Najbaner J, Woo CC, Dashtipour K, Ribak CE and Leon M. (2001).
Expression of active caspase-3 in mitotic and postmitotic cells of the rat forebrain. J. Comp. Neurol. 433, 4-22.
Yang X, Chang HY and Baltimore D.(1998). Autoproteolytic activation of pro-caspases by oligomerization. Mol. Cell 1, 319-325.
Yang XM, Hou LJ, Dong DJ, Shao HL, Wang JX and Zhao XF. (2006). Cathepsin B-like proteinase is involved in the decomposition of the adult fat body of Helicoverpa armigera. Arch. Insect Biochem. Physiol. 62,1-10.
Yang XM, Hou LJ, Wang JX, and Zhao XF. (2007). Expression and Function of Cathepsin B-Like Proteinase in Larval Hemocytes of Helicorverpa armigera during Metamorphosis. Arch. Insect Biochem. Physiol. (in press).
Yin VP and Thummel CS. (2005). Mechanisms of steroid-triggered programmed cell death in Drosophila. Semin. Cell Dev. Biol. 16,237-243.
Yokoyama H, Mukae N, Sakahira H, Okawa K, Iwamatsu A and Nagata S. (2000). A novel activation mechanism of caspase-activated DNase from Drosophila melanogaster.J. Biol. Chem. 275,12978-12986.
Yokokura T, Dresnek D, Huseinovic N, Lisi S, Abdelwahid E, Bangs P and White K. (2004). Dissection of DIAP1 functional domains via a mutant replacement strategy. J. Biol. Chem. 279, 52603-52612.
Yuan J, Shaham S, Ledoux S, Ellis HM and Horvitz HR. (1993). The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell 75, 641-652.
Zakeri Z and Lockshin RA. (2002). Cell death during development. J. Immunol. Methods 265, 3-20.
Zandy AJ, Lakhani S, Zheng T, Flavell RA and Bassnett S. (2005). Role of the executioner caspases during lens development. J. Biol Chem. 280,30263-30272.
Zhao C and Wang E. (2004). Heat shock protein 90 suppresses tumor necrosis factor alpha induced apoptosis by preventing the cleavage of Bid in NIH3T3 fibroblasts. Cell Signal 16,313-321.
Zhao XF, Wang JX and Wang YC. (1998). Purification and characterization of a cysteine proteinase from eggs of the cotton boll worm, Helicoverpa armigera. Insect Biochem. Mol. Biol.. 28, 259-264.
Zhao XF, Wang JX, Xu XL, Schmid R. and Wiecxorek H. (2002). Molecular cloning and characterization of cathepsin B-like proteinase from the cotton boll worm Helicoverpa armigera. Insect Mol. Biol. 11,567-575.
Zhou L, Schnitzler A, Agapite J, Schwartz LM, Steller H and Nambu JR.(1997).
Cooperative functions of the reaper and head involution defective genes in the programmed cell death of Drosophila central nervous system midline cells. Proc. Natl. Acad. Sci. 94, 5131-5136.
Zhou Q, Krebs JF, Snipas SJ, Price A, Alnemri ES, Tomaselli KJ and Salvesen GS. (1998). Interaction of the baculovirus anti-apoptotic protein p35 with caspases. Specificity, kinetics, and characterization of the caspase/p35 complex. Biochemistry 37, 10757-10765.
Zugel U, Sponaas AM, Neckermann J, Schoel B and Kaufmann SH.(2001). gp96-peptide vaccination of mice against intracellular bacteria. Infect Immun. 69, 4164-4167.
康翠洁。中国对虾先天免疫相关基因克隆与表达研究。山东大学博士论文。2004。