青藏高原高寒草甸小哺乳动物p53基因适应进化变异研究
|
摘要
p53作为一种转录因子,在应激状态下通过控制多种靶基因的表达来诱导细胞周期停滞或程序性死亡,以保证细胞基因组的完整性并决定细胞命运。同时,各物种在长期环境适应进化中,p53也会发生各种修饰变异,以适应物种自身特定的生境和生活习性。高原鼢鼠(Myospalax Baileyi, Thomas,1911)和根田鼠(Microtus oeconomus, Pallas,1776)世居青藏高原高寒草甸(海拔3300m),前者栖居于退化的高寒草甸,后者栖居于金露梅灌丛草甸,为青藏高原优势种小型哺乳动物。高原鼢鼠常年营地下洞道生活,根田鼠半地下生活。生境长年低氧和寒冷。
通过克隆p53基因编码区和序列分析,研究了高原鼢鼠和根田鼠p53基因变异,发现p53基因序列与人类,大鼠,小鼠p53有不同程度的相似性,但高原鼢鼠p53在核心区的104,127,215位和C端的322位及根田鼠p53N端的86位,核心区的104,258位和C端的340位发生变异。
研究高原鼢鼠和根田鼠p53对靶基因的转录调控,发现高原鼢鼠p53对促凋亡靶基因IGFBP3和Apafl的转录激活显著高于人类p53,而根田鼠p53对这两个靶基因的转录激活显著低于人类p53。两种动物的p53对诱导周期停滞的靶基因p21和参与p53稳定性调节的靶基因Hdm2转录激活与人类p53相似。变异位点研究显示,高原鼢鼠p53第104位点Ser转变成Asn的突变与其高促凋亡基因转录有关,而根田鼠p53第104位点Ser转变成Glu的突变是造成其低促凋亡基因转录的关键。
对两种动物p53影响细胞命运的研究显示,根田鼠p53诱导细胞凋亡的能力显著低于人类p53,将104位点突变为与人类对应的Ser使促凋亡能力升高一倍,说明根田鼠p53的低促凋亡能力是由于104位点的Ser→Glu造成的。这可能是根田鼠适应低氧环境,避免低氧诱导凋亡的策略之一。高原鼢鼠p53诱导凋亡能力与人类p53接近,因为在高原鼢鼠p53转录激活促凋亡靶基因IGFBP3和Apafl的同时,它失去了对保护凋亡的靶基因Bcl-2的转录抑制,反而使其转录水平升高,从而与促凋亡靶基因的高转录水平相抗衡。研究还发现,酸性环境下p53对IGFBP3的转录活性降低,使Bcl-2的转录水平升高,提示高原鼢鼠在低氧、高二氧化碳环境中,促凋亡与抗凋亡的内环境平衡对策,趋向抗凋亡的平衡,这可能是高原鼢鼠适应生境低氧／高二氧化碳的策略之一。
本研究通过基因克隆等分子生物学手段,首次发现了高原鼢鼠和根田鼠p53基因的长期适应进化变异,展示特定的位点；这些变异表现出对代表性促凋亡靶基因的反向转录激活模式,也表现出不同的诱导细胞凋亡能力,体现了高原动物在转录水平上对低氧环境适应的多模式化机制。这些变异可能是对高原环境长期适应进化的基因分子机制。
As a transcription factor, p53induces cell cycle arrest and apoptosis under stresses through a series of target genes to maintain the genome integrity and determine the cell fate. Myospalax baileyi (Thomas,1911) and Microtus oeconomus (Pallas,1776) inhabit the meadow at3300m altitude on the Qinghai-Tibetan plateau. The former lives in the degenerative alpine meadow and the latter lives in the shrub meadow of Potentilla fruticosa. Both of them are dominant species of Qinghai-Tibetan Plateau. The Myospalax baileyi spends its whole life cycle in burrows underground. The Microtus oeconomus leads a semi-underground life. They bear a hypoxic and cold environment.
The mutation of the p53genes from Myospalax baileyi and Microtus oeconomus was analyzed by cloning and sequencing the p53gene. Their p53genes have analogies with that of human, rat and mouse to different degrees. The codon104,127,215in the core domain and322in the C-terminus of Myospalax baileyi p53and the codon86in the N-terminus,104,258in the core domain and340in the C-terminus of Microtus oeconomus p53mutated.
Investigating the transcriptional regulation of Myospalax and Microtus p53towards target genes showed that the Myospalax p53has a significantly higher transactivationg towards the pro-apoptotic targets IGFBP3and Apafl; the Microtus p53, however, has a much lower transactivation towards these two target genes. Both Myospalax and Microtus p53has a similar ability to transactivate p21(involved in cell cycle arrest) and Hdm2(involved in p53homeostasis) with that of human p53. Mutagenesis experiments demonstrated that the mutation of the codon104from Ser to Asn of the Myospalax p53is related with its strong transactivation towards the pro-apoptotic target genes. The mutation of the codon104from Ser to Glu of the Microtus p53is critical for its weak transactivation towards the pro-apoptotic target genes.
Study on the influence of Myospalax and Microtus p53on cell fate showed that, the Microtus p53has a significantly weaker capability to induce apoptosis. Humanization of the codon104increased the pro-apoptotic ability, suggesting that the weaker pro-apoptotic ability of Microtus p53is due to the mutation S104E. This may be the strategy of Microtus to adapt to the hypoxic habitat by preventing the hypoxia-induced apoptosis. The Myospalax p53has a similar capability to induce apoptosis with that of human p53. Although the Myospalax p53has stronger transactivation towards the pro-apoptotic target gene IGFBP3and Apafl, it lost the transrepression towards the antiapoptotic gene Bcl-2, and even induced a transactivation of Bcl-2. The antiapoptotic and pro-apoptotic ability form a balance.
Our study also demonstrated that, the capability of p53transactivation towards IGFBP3decreased while Bcl-2increased under acidic environment, suggesting that, under hypoxia/high CO2environment, the balance of antiapoptotic and pro-apoptotic ability prefers the antiapoptotic ability. This may serves as a strategy for Myospalax adaptation to hypoxia/high CO2environment.
The present study used molecular cloning strategies to demonstrate the mutated sites of Myospalax and Microtus p53. These mutants showed reverse transcriptional patterns towards pro-apoptotic target genes, with different pro-apoptotic capabilities. The results reflected the diversity of transcriptional mechanisms adapting to hypoxia enviorment. The mutations may be the molecular mechanisms of adaptation to the plateau environment during evolution.
通过克隆p53基因编码区和序列分析,研究了高原鼢鼠和根田鼠p53基因变异,发现p53基因序列与人类,大鼠,小鼠p53有不同程度的相似性,但高原鼢鼠p53在核心区的104,127,215位和C端的322位及根田鼠p53N端的86位,核心区的104,258位和C端的340位发生变异。
研究高原鼢鼠和根田鼠p53对靶基因的转录调控,发现高原鼢鼠p53对促凋亡靶基因IGFBP3和Apafl的转录激活显著高于人类p53,而根田鼠p53对这两个靶基因的转录激活显著低于人类p53。两种动物的p53对诱导周期停滞的靶基因p21和参与p53稳定性调节的靶基因Hdm2转录激活与人类p53相似。变异位点研究显示,高原鼢鼠p53第104位点Ser转变成Asn的突变与其高促凋亡基因转录有关,而根田鼠p53第104位点Ser转变成Glu的突变是造成其低促凋亡基因转录的关键。
对两种动物p53影响细胞命运的研究显示,根田鼠p53诱导细胞凋亡的能力显著低于人类p53,将104位点突变为与人类对应的Ser使促凋亡能力升高一倍,说明根田鼠p53的低促凋亡能力是由于104位点的Ser→Glu造成的。这可能是根田鼠适应低氧环境,避免低氧诱导凋亡的策略之一。高原鼢鼠p53诱导凋亡能力与人类p53接近,因为在高原鼢鼠p53转录激活促凋亡靶基因IGFBP3和Apafl的同时,它失去了对保护凋亡的靶基因Bcl-2的转录抑制,反而使其转录水平升高,从而与促凋亡靶基因的高转录水平相抗衡。研究还发现,酸性环境下p53对IGFBP3的转录活性降低,使Bcl-2的转录水平升高,提示高原鼢鼠在低氧、高二氧化碳环境中,促凋亡与抗凋亡的内环境平衡对策,趋向抗凋亡的平衡,这可能是高原鼢鼠适应生境低氧／高二氧化碳的策略之一。
本研究通过基因克隆等分子生物学手段,首次发现了高原鼢鼠和根田鼠p53基因的长期适应进化变异,展示特定的位点；这些变异表现出对代表性促凋亡靶基因的反向转录激活模式,也表现出不同的诱导细胞凋亡能力,体现了高原动物在转录水平上对低氧环境适应的多模式化机制。这些变异可能是对高原环境长期适应进化的基因分子机制。
As a transcription factor, p53induces cell cycle arrest and apoptosis under stresses through a series of target genes to maintain the genome integrity and determine the cell fate. Myospalax baileyi (Thomas,1911) and Microtus oeconomus (Pallas,1776) inhabit the meadow at3300m altitude on the Qinghai-Tibetan plateau. The former lives in the degenerative alpine meadow and the latter lives in the shrub meadow of Potentilla fruticosa. Both of them are dominant species of Qinghai-Tibetan Plateau. The Myospalax baileyi spends its whole life cycle in burrows underground. The Microtus oeconomus leads a semi-underground life. They bear a hypoxic and cold environment.
The mutation of the p53genes from Myospalax baileyi and Microtus oeconomus was analyzed by cloning and sequencing the p53gene. Their p53genes have analogies with that of human, rat and mouse to different degrees. The codon104,127,215in the core domain and322in the C-terminus of Myospalax baileyi p53and the codon86in the N-terminus,104,258in the core domain and340in the C-terminus of Microtus oeconomus p53mutated.
Investigating the transcriptional regulation of Myospalax and Microtus p53towards target genes showed that the Myospalax p53has a significantly higher transactivationg towards the pro-apoptotic targets IGFBP3and Apafl; the Microtus p53, however, has a much lower transactivation towards these two target genes. Both Myospalax and Microtus p53has a similar ability to transactivate p21(involved in cell cycle arrest) and Hdm2(involved in p53homeostasis) with that of human p53. Mutagenesis experiments demonstrated that the mutation of the codon104from Ser to Asn of the Myospalax p53is related with its strong transactivation towards the pro-apoptotic target genes. The mutation of the codon104from Ser to Glu of the Microtus p53is critical for its weak transactivation towards the pro-apoptotic target genes.
Study on the influence of Myospalax and Microtus p53on cell fate showed that, the Microtus p53has a significantly weaker capability to induce apoptosis. Humanization of the codon104increased the pro-apoptotic ability, suggesting that the weaker pro-apoptotic ability of Microtus p53is due to the mutation S104E. This may be the strategy of Microtus to adapt to the hypoxic habitat by preventing the hypoxia-induced apoptosis. The Myospalax p53has a similar capability to induce apoptosis with that of human p53. Although the Myospalax p53has stronger transactivation towards the pro-apoptotic target gene IGFBP3and Apafl, it lost the transrepression towards the antiapoptotic gene Bcl-2, and even induced a transactivation of Bcl-2. The antiapoptotic and pro-apoptotic ability form a balance.
Our study also demonstrated that, the capability of p53transactivation towards IGFBP3decreased while Bcl-2increased under acidic environment, suggesting that, under hypoxia/high CO2environment, the balance of antiapoptotic and pro-apoptotic ability prefers the antiapoptotic ability. This may serves as a strategy for Myospalax adaptation to hypoxia/high CO2environment.
The present study used molecular cloning strategies to demonstrate the mutated sites of Myospalax and Microtus p53. These mutants showed reverse transcriptional patterns towards pro-apoptotic target genes, with different pro-apoptotic capabilities. The results reflected the diversity of transcriptional mechanisms adapting to hypoxia enviorment. The mutations may be the molecular mechanisms of adaptation to the plateau environment during evolution.
引文
1. Asker C, Wiman KG, Selivanova G p53-induced apoptosis as a safeguard against cancer. Biochem Biophys Res Commun,1999,265(1):1-6.
2. Avivi A, Ashur-Fabian O, Amariglio N, Nevo E, Rechavi G. p53-a key player in tumoral and evolutionary adaptation: a lesson from the Israeli blind subterranean mole rat. Cell Cycle,2005,4(3): 368-372.
3. Cai Y, Du JZ. Comparative physiology in China 1984-2007. Comp Biochem Physiol C Toxicol Pharmacol,2008,148(4):296-304.
4. Cao YB, Chen XQ, Wang S, Chen XC, Wang YX, Chang JP, Du JZ. Growth hormone and insulin-like growth factor of naked carp (Gymnocypris przewalskii) in Lake Qinghai:expression in different water environments. Gen Comp Endocrinol,2009,161(3):400-406.
5. Cao YB, Chen XQ, Wang S, Wang YX, Du JZ. Evolution and regulation of the downstream gene of hypoxia-inducible factor-1 alpha in naked carp (Gymnocypris przewalskii) from Lake Qinghai, China. J Mol Evol,2008, 67(5):570-580.
6. Chen XQ, Wang SJ, Du JZ, Chen XC. Diversities in hepatic HIF-1, IGF-I/IGFBP-1, LDH/ICD, and their mRNA expressions induced by CoCl(2) in Qinghai-Tibetan plateau mammals and sea level mice. Am J Physiol Regul Integr Comp Physiol,2007,292(1):R516-526.
7. Du JZ, Li QF, Chen XG. The changing of corticosterone level in native Ochotona curzoniae. Acta Theriologica Sinica,1983,3(1):47-52.
8. Du JZ, Li QF, Chen XG. Effect of Simulated Altitude on liver of Ochotona curzoniae and rats. Acta Zool. Fennica,1984,171:201-203.
9. Du JZ, Wang Y, Brauner C, Richards J, Chen X. "Diversity in a changing environment"-the International Conference of Comparative Physiology, Biochemistry and Toxicology and 6th Chinese Comparative Physiology Conference. Comp Biochem Physiol C Toxicol Pharmacol,2008, 148(4):293-295.
10. Du JZ, Zhou ZQ. Report on the 5th Comparative Physiology Conference of Chinese Association for Physiological Sciences. Comp Biochem Physiol A Physiol 2005,140:257-273.
11. Glazko GV, Koonin EV, Rogozin IB. Mutation hotspots in the p53 gene in tumors of different origin:correlation with evolutionary conservation and signs of positive selection. Biochim Biophys Acta,2004,1679(2):95-106.
12. Hernandez I, Maddison LA, Wei Y, DeMayo F, Petras T, Li B, Gingrich JR, Rosen JM, Greenberg NM. Prostate-specific expression of p53(R172L) differentially regulates p21, Bax, and mdm2 to inhibit prostate cancer progression and prolong survival. Mol Cancer Res,2003,1 (14):1036-1047.
13. Klein G. Cancer, apoptosis, and nonimmune surveillance. Cell Death Differ, 2004,11(1):13-17.
14. Li QF, Chen XG, You ZB, Du JZ. A comparative study on effects of acute hypoxia upon livers of three small mammals. Acta Theriologica Sinica 1987, 7(1):51-57.
15. Li QF, Du JZ. Effect of chronic hypoxia on liver of Ochotona curzoniae and rat. Acta Theriologica Sinica,1986,6(4):261-266.
16. Matey V, Richards JG, Wang Y, Wood CM, Rogers J, Davies R, Murray BW, Chen XQ, Du J, Brauner CJ. The effect of hypoxia on gill morphology and ionoregulatory status in the Lake Qinghai scaleless carp, Gymnocypris przewalskii. J Exp Biol,2008,211(Pt 7):1063-1074.
17. Miled C, Pontoglio M, Garbay S, Yaniv M, Weitzman JB. A genomic map of p53 binding sites identifies novel p53 targets involved in an apoptotic network. Cancer Res,2005,65(12):5096-5104.
18. O'Bryan DM, Xie Z, Wang Y, Du J, Brauner CJ, Richards JG, Wood CM, Chen XQ, Murray BW. Phylogeography and conservation genetics of Lake Qinghai scaleless carp Gymnocypris przewalskii. J Fish Biol,2010,77(9):2072-2092.
19. Pietenpol JA, Tokino T, Thiagalingam S, el-Deiry WS, Kinzler KW, Vogelstein B. Sequence-specific transcriptional activation is essential for growth suppression by p53. Proc Natl Acad Sci USA,1994,91(6):1998-2002.
20. Soussi T, Caron de Fromentel C, May P. Structural aspects of the p53 protein in relation to gene evolution. Oncogene,1990,5(7):945-952.
21. Soussi T, May P. Structural aspects of the p53 protein in relation to gene evolution:a second look. JMol Biol,1996,260(5):623-637.
22. Wei DB, Wei L, Zhang JM, Yu HY. Blood-gas properties of plateau zokor (Myospalax baileyi). Comp Biochem Physiol A Mol Integr Physiol,2006, 145(3):372-375.
23. Wood CM, Du J, Rogers J, Brauner CJ, Richards JG, Semple JW, Murray BW, Chen XQ, Wang Y. Przewalski's naked carp (Gymnocypris przewalskii):an endangered species taking a metabolic holiday in Lake Qinghai, China. Physiol Biochem Zool,2007,80(1):59-77.
24. Zhao Y, Chen XQ, Du JZ. Cellular adaptation to hypoxia and p53 transcription regulation. J Zhejiang Univ Sci B,2009,10(5):404-410.
25. 吕永达,霍仲厚.(2005)特殊环境生理学(军事医学科学院出版社).
1. Appella E,Anderson CW. Post-translational modifications and activation of p53 by genotoxic stresses. Eur J Biochem,2001,268(10):2764-2772.
2. Arnold K, Bordoli L, Kopp J, Schwede T. The SWISS-MODEL workspace:a web-based environment for protein structure homology modelling. Bioinformatics,2006,22(2):195-201.
3. Ashur-Fabian O, Avivi A, Trakhtenbrot L, Adamsky K, Cohen M, Kajakaro G, Joel A, Amariglio N, Nevo E, Rechavi G. Evolution of p53 in hypoxia-stressed Spalax mimics human tumor mutation. Proc Natl Acad Sci U S A,2004, 101 (33):12236-12241.
4. Asker C, Wiman KG, Selivanova G. p53-induced apoptosis as a safeguard against cancer. Biochem Biophys Res Commun,1999,265(1):1-6.
5. Avivi A, Ashur-Fabian O, Amariglio N, Nevo E, Rechavi G. p53--a key player in tumoral and evolutionary adaptation:a lesson from the Israeli blind subterranean mole rat. Cell Cycle,2005,4(3):368-372.
6. Baker SJ, Fearon ER, Nigro JM, Hamilton SR, Preisinger AC, Jessup JM, vanTuinen P, Ledbetter DH, Barker DF, Nakamura Y, White R, Vogelstein B. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science,1989,244(4901):217-221.
7. Bargonetti J, Manfredi JJ, Chen X, Marshak DR, Prives C. A proteolytic fragment from the central region of p53 has marked sequence-specific DNA-binding activity when generated from wild-type but not from oncogenic mutant p53 protein. Genes Dev,1993,7(12B):2565-2574.
8. Brodsky LI, Jacob-Hirsch J, Avivi A, Trakhtenbrot L, Zeligson S, Amariglio N, Paz A, Korol AB, Band M, Rechavi G, Nevo E. Evolutionary regulation of the blind subterranean mole rat, Spalax, revealed by genome-wide gene expression. Proc Natl Acad Sci USA,2005,102(47):17047-17052.
9. Brodsky MH, Nordstrom W, Tsang G, Kwan E, Rubin GM, Abrams JM. Drosophila p53 binds a damage response element at the reaper locus. Cell, 2000,101(1):103-113.
10. Brunhoff C, Galbreath KE, Fedorov VB, Cook JA, Jaarola M. Holarctic phylogeography of the root vole (Microtus oeconomus):implications for late Quaternary biogeography of high latitudes. Mol Ecol,2003,12(4):957-968.
11. Cho Y, Gorina S, Jeffrey PD, Pavletich NP. Crystal structure of a p53 tumor suppressor-DNA complex:understanding tumorigenic mutations. Science,1994, 265(5170):346-355.
12. Clore GM, Ernst J, Clubb R, Omichinski JG, Kennedy WM, Sakaguchi K, Appella E, Gronenborn AM. Refined solution structure of the oligomerization domain of the tumour suppressor p53. Nat Struct Biol,1995,2(4):321-333.
13. Derry WB, Putzke AP, Rothman JH. Caenorhabditis elegans p53:role in apoptosis, meiosis, and stress resistance. Science,2001,294(5542):591-595.
14. el-Deiry WS. Regulation of p53 downstream genes. Semin Cancer Biol,1998, 8(5):345-357.
15. Fleck CC,Carey HV. Modulation of apoptotic pathways in intestinal mucosa during hibernation. Am J Physiol Regul Integr Comp Physiol,2005, 289(2):R586-R595.
16. Glazko GV, Koonin EV, Rogozin IB. Mutation hotspots in the p53 gene in tumors of different origin:correlation with evolutionary conservation and signs of positive selection. Biochim Biophys Acta,2004,1679(2):95-106.
17. Gu W, Shi XL, Roeder RG. Synergistic activation of transcription by CBP and p53. Nature,1997,387(6635):819-823.
18. Guex N,Peitsch MC. SWISS-MODEL and the Swiss-PdbViewer:an environment for comparative protein modeling. Electrophoresis,1997, 18(15):2714-2723.
19. Hammond EM,Giaccia AJ. The role of p53 in hypoxia-induced apoptosis. Biochem Biophys Res Commun,2005,331 (3):718-725.
20. Hammond EM, Mandell DJ, Salim A, Krieg AJ, Johnson TM, Shirazi HA, Attardi LD, Giaccia AJ. Genome-wide analysis of p53 under hypoxic conditions. Mol Cell Biol,2006,26(9):3492-3504.
21. Humphrey W, Dalke A, Schulten K. VMD:visual molecular dynamics. J Mol Graph,1996,14(l):33-38,27-38.
22. Koumenis C, Alarcon R, Hammond E, Sutphin P, Hoffman W, Murphy M, Derr J, Taya Y, Lowe SW, Kastan M, Giaccia A. Regulation of p53 by hypoxia: dissociation of transcriptional repression and apoptosis from p53-dependent transactivation. Mol Cell Biol,2001,21 (4):1297-1310.
23. Kruse JP,Gu W. Modes of p53 regulation. Cell,2009,137(4):609-622.
24. Lane DP,Crawford LV. T antigen is bound to a host protein in SV40-transformed cells. Nature,1979,278(5701):261-263.
25. Lee S, Elenbaas B, Levine A, Griffith J. p53 and its 14 kDa C-terminal domain recognize primary DNA damage in the form of insertion/deletion mismatches. Cell,1995,81(7):1013-1020.
26. Levine AJ. p53, the cellular gatekeeper for growth and division. Cell,1997, 88(3):323-331.
27. Liang SH,Clarke MF. The nuclear import of p53 is determined by the presence of a basic domain and its relative position to the nuclear localization signal. Oncogene,1999,18(12):2163-2166.
28. Miled C, Pontoglio M, Garbay S, Yaniv M, Weitzman JB. A genomic map of p53 binding sites identifies novel p53 targets involved in an apoptotic network. Cancer Res,2005,65(12):5096-5104.
29. Murphy M, Ahn J, Walker KK, Hoffman WH, Evans RM, Levine AJ, George DL. Transcriptional repression by wild-type p53 utilizes histone deacetylases, mediated by interaction with mSin3a. Genes Dev,1999,13(19):2490-2501.
30. Pietenpol JA, Tokino T, Thiagalingam S, el-Deiry WS, Kinzler KW, Vogelstein B. Sequence-specific transcriptional activation is essential for growth suppression by p53. Proc Natl Acad Sci U S A,1994,91 (6):1998-2002.
31. Rau Embry M, Billiard SM, Di Giulio RT. Lack of p53 induction in fish cells by model chemotherapeutics. Oncogene,2006,25(14):2004-2010.
32. Sakaguchi K, Herrera JE, Saito S, Miki T, Bustin M, Vassilev A, Anderson CW, Appella E. DNA damage activates p53 through a phosphorylation-acetylation cascade. Genes Dev,1998,12(18):2831-2841.
33. Schwede T, Kopp J, Guex N, Peitsch MC. SWISS-MODEL:An automated protein homology-modeling server. Nucleic Acids Re.s,2003, 31(13):3381-3385.
34. Shaulsky G, Goldfinger N, Ben-Ze'ev A, Rotter V. Nuclear accumulation of p53 protein is mediated by several nuclear localization signals and plays a role in tumorigenesis. Mol Cell Biol,1990,10(12):6565-6577.
35. Sionov RV,Haupt Y. The cellular response to p53:the decision between life and death. Oncogene,1999,18(45):6145-6157.
36. Soussi T, Caron de Fromentel C, May P. Structural aspects of the p53 protein in relation to gene evolution. Oncogene,1990,5(7):945-952.
37. Soussi T,May P. Structural aspects of the p53 protein in relation to gene evolution:a second look. JMol Biol,1996,260(5):623-637.
38. Stommel JM, Marchenko ND, Jimenez GS, Moll UM, Hope TJ, Wahl GM. A leucine-rich nuclear export signal in the p53 tetramerization domain:regulation of subcellular localization and p53 activity by NES masking. EMBO J,1999, 18(6):1660-1672.
39. Thut CJ, Chen JL, Klemm R, Tjian R. p53 transcriptional activation mediated by coactivators TAFII40 and TAFII60. Science,1995,267(5194):100-104.
40. Villiard E, Brinkmann H, Moiseeva O, Mallette FA, Ferbeyre G, Roy S. Urodele p53 tolerates amino acid changes found in p53 variants linked to human cancer. BMC Evol Biol,2007,7:180.
41. Vousden KH,Prives C. Blinded by the Light:The Growing Complexity of p53. Cell,2009,137(3):413-431.
42. Walker KK,Levine AJ. Identification of a novel p53 functional domain that is necessary for efficient growth suppression. Proc Natl Acad Sci U S A,1996, 93(26):15335-15340.
43. Wang BQ, Kostrub CF, Finkelstein A, Burton ZF. Production of human RAP30 and RAP74 in bacterial cells. Protein Expr Purif,1993,4(3):207-214.
44. Wei DB, Wei L, Zhang JM, Yu HY. Blood-gas properties of plateau zokor (Myospalax baileyi). Comp Biochem Physiol A Mol Integr Physiol,2006, 145(3):372-375.
45. Yang Z. PAML:a program package for phylogenetic analysis by maximum likelihood. Comput Appl Biosci,1997,13(5):555-556.
46. 邴积才，张三亮,郭文辉,强维秀,汪有奎.中华鼢鼠、甘肃鼢鼠发生规律研究.甘肃林业科技2001,26(2)：12-15.
47. 樊乃昌,施银柱.中国鼢鼠(Eospalax)亚属分类研究.兽类学报,1982,2(2)：183-199.
48. 王晓君,魏登邦,魏莲,张建梅,于红妍.高原鼢鼠和高原鼠兔红细胞低氧适应特征.四川动物2008,27(6)：1100-1103.
49. 王玉山,王德华,王祖望.高原鼠兔和根田鼠的最大代谢率.动物学报,2001,47(6)：601-608.
50. 魏登邦,魏莲.高原鼢鼠的红细胞、血红蛋白及肌红蛋白的测定结果.青海大学学报：自然科学版，2001,19(4)：1-2,12.
51. 魏登邦,张建梅,魏莲,于红妍，王晓君.高原鼢鼠对低氧高二氧化碳环境适应的相关血液生理指标的季节变化.动物学报,2006,52(5)：871-877.
1. Alarcon R, Koumenis C, Geyer RK, Maki CG, Giaccia AJ. Hypoxia induces p53 accumulation through MDM2 down-regulation and inhibition of E6-mediated degradation. Cancer Res,1999,59(24):6046-6051.
2. Ashur-Fabian O, Avivi A, Trakhtenbrot L, Adamsky K, Cohen M, Kajakaro G, Joel A, Amariglio N, Nevo E, Rechavi G. Evolution of p53 in hypoxia-stressed Spalax mimics human tumor mutation. Proc Natl Acad Sci U S A,2004, 101(33):12236-12241.
3. Asker C, Wiman KG, Selivanova G. p53-induced apoptosis as a safeguard against cancer. Biochem Biophys Res Commun,1999,265(1):1-6.
4. Avivi A, Ashur-Fabian O, Amariglio N, Nevo E, Rechavi G. p53--a key player in tumoral and evolutionary adaptation:a lesson from the Israeli blind subterranean mole rat. Cell Cycle,2005,4(3):368-372.
5. Bronstein I, Martin CS, Fortin JJ, Olesen CE, Voyta JC. Chemiluminescence: sensitive detection technology for reporter gene assays. Clin Chem,1996, 42(9):1542-1546.
6. Chene P. The role of tetramerization in p53 function. Oncogene,2001, 20(21):2611-2617.
7. Chitayat S,Arrowsmith CH. Four p(53)s in a pod. Nat Struct Mol Biol,2010, 17(4):390-391.
8. Dittmer D, Pati S, Zambetti G, Chu S, Teresky AK, Moore M, Finlay C, Levine AJ. Gain of function mutations in p53. Nat Genet,1993,4(1):42-46.
9. Dyer BW, Ferrer FA, Klinedinst DK, Rodriguez R. A noncommercial dual luciferase enzyme assay system for reporter gene analysis. Anal Biochem,2000, 282(1):158-161.
10. el-Deiry WS. Regulation of p53 downstream genes. Semin Cancer Biol,1998, 8(5):345-357.
11. Hernandez I, Maddison LA, Wei Y, DeMayo F, Petras T, Li B, Gingrich JR, Rosen JM, Greenberg NM. Prostate-specific expression of p53(R172L) differentially regulates p21, Bax, and mdm2 to inhibit prostate cancer progression and prolong survival. Mol Cancer Res,2003,1(14):1036-1047.
12. Hjelmeland AB, Wu Q, Heddleston JM, Choudhary GS, Macswords J, Lathia JD, McLendon R, Lindner D, Sloan A, Rich JN. Acidic stress promotes a glioma stem cell phenotype. Cell Death Differ,2010.
13. Hjelmeland AB, Wu Q, Heddleston JM, Choudhary GS, MacSwords J, Lathia JD, McLendon R, Lindner D, Sloan A, Rich JN. Acidic stress promotes a glioma stem cell phenotype. Cell Death Differ,2011,18(5):829-840.
14. Jorgensen JB,Mustafa T. The effect of hypoxia on carbohydrate metabolism in flounder (Platichthys flesus L.)I. Utilization of glycogen and accumulation of glycolytic end products in various tissues. Comp Biochem Physiol B,1980, 67:243-248.
15. Kallinowski F,Vaupel P. pH distributions in spontaneous and isotransplanted rat tumours. BrJ Cancer,1988,58(3):314-321.
16. Kato S, Han SY, Liu W, Otsuka K, Shibata H, Kanamaru R, Ishioka C. Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis. ProcNatl Acad Sci U S A,2003,100(14):8424-8429.
17. Kazianis S, Gan L, Della Coletta L, Santi B, Morizot DC, Nairn RS. Cloning and comparative sequence analysis of TP53 in Xiphophorus fish hybrid melanoma models. Gene,1998,212(1):31-38.
18. Kimura K, Shinmura K, Hasegawa T, Beppu Y, Yokoyama R, Yokota J. Germline p53 mutation in a patient with multiple primary cancers. Jpn J Clin Oncol,2001,31(7):349-351.
19. Kitayner M, Rozenberg H, Kessler N, Rabinovich D, Shaulov L, Haran TE, Shakked Z. Structural basis of DNA recognition by p53 tetramers. Mol Cell, 2006,22(6):741-753.
20. Kitayner M, Rozenberg H, Rohs R, Suad O, Rabinovich D, Honig B, Shakked Z. Diversity in DNA recognition by p53 revealed by crystal structures with Hoogsteen base pairs. Nat Struct Mol Biol,2010,17(4):423-429.
21. Klein G. Cancer, apoptosis, and nonimmune surveillance. Cell Death Differ, 2004,11(1):13-17.
22. Koumenis C, Alarcon R, Hammond E, Sutphin P, Hoffman W, Murphy M, Derr J, Taya Y, Lowe SW, Kastan M, Giaccia A. Regulation of p53 by hypoxia: dissociation of transcriptional repression and apoptosis from p53-dependent transactivation. Mol Cell Biol,2001.21 (4):1297-1310.
23. Loh SN. The missing zinc:p53 misfolding and cancer. Metallomics,2010, 2(7):442-449.
24. Lundgreen K, Kiilerich P, Tipsmark CK, Madsen SS, Jensen FB. Physiological response in the European flounder (Platichthys flesus) to variable salinity and oxygen conditions. J Comp Physiol B,2008,178(7):909-915.
25. Miled C, Pontoglio M, Garbay S, Yaniv M, Weitzman JB. A genomic map of p53 binding sites identifies novel p53 targets involved in an apoptotic network. Cancer Res,2005,65(12): 5096-5104.
26. Nagaraj NS, Singh OV, Merchant NB. Proteomics:a strategy to understand the novel targets in protein misfolding and cancer therapy. Expert Rev Proteomics, 2010,7(4):613-623.
27. Pan Y, Oprysko PR, Asham AM, Koch CJ, Simon MC. p53 cannot be induced by hypoxia alone but responds to the hypoxic microenvironment. Oncogene, 2004,23(29):4975-4983.
28. Parks SK, Chiche J, Pouyssegur J. pH control mechanisms of tumor survival and growth. J Cell Physiol,2011,226(2):299-308.
29. Reichert M, Steinbach JP, Supra P, Weller M. Modulation of growth and radiochemosensitivity of human malignant glioma cells by acidosis. Cancer, 2002,95(5):1113-1119.
30. Ryan KM,Vousden KH. Characterization of structural p53 mutants which show selective defects in apoptosis but not cell cycle arrest. Mol Cell Biol,1998, 18(7):3692-3698.
31. Scian MJ, Carchman EH, Mohanraj L, Stagliano KE, Anderson MA, Deb D, Crane BM, Kiyono T, Windle B, Deb SP, Deb S. Wild-type p53 and p73 negatively regulate expression of proliferation related genes. Oncogene,2008, 27(18):2583-2593.
32. Tschop K,Engeland K. Cell cycle-dependent transcription of cyclin B2 is influenced by DNA methylation but is independent of methylation in the CDE and CHR elements. FEBS J,2007,274(20):5235-5249.
33. Villiard E, Brinkmann H, Moiseeva O, Mallette FA, Ferbeyre G, Roy S. Urodele p53 tolerates amino acid changes found in p53 variants linked to human cancer. BMC Evol Biol,2007,7:180.
34. 魏登邦,魏莲,张建梅,于红妍,王晓君.地下鼠对洞道环境适应的研究进展.青海大学学报(自然科学版夕,2007,25(5)：54-57.
35. 魏登邦,张建梅,魏莲,于红妍,王晓君.高原鼢鼠对低氧高二氧化碳环境适应的相关血液生理指标的季节变化.动物学报2006,52(5)：871-877.
1. Bratton SB,Salvesen GS. Regulation of the Apaf-l-caspase-9 apoptosome. J Cell Sci,2010,123(Pt 19):3209-3214.
2. Budhram-Mahadeo V, Morris PJ, Smith MD, Midgley CA, Boxer LM, Latchman DS. p53 suppresses the activation of the Bcl-2 promoter by the Brn-3a POU family transcription factor. J Biol Chem,1999, 274(21):15237-15244.
3. Han J, Jogie-Brahim S, Harada A, Oh Y. Insulin-like growth factor-binding protein-3 suppresses tumor growth via activation of caspase-dependent apoptosis and cross-talk with NF-kappaB signaling. Cancer Lett,2011, 307(2):200-210.
4. Ingermann AR, Yang YF, Han J, Mikami A, Garza AE, Mohanraj L, Fan L, Idowu M, Ware JL, Kim HS, Lee DY, Oh Y. Identification of a novel cell death receptor mediating IGFBP-3-induced anti-tumor effects in breast and prostate cancer. J Biol Chem,2010,285(39):30233-30246.
5. Kim HS, Ingermann AR, Tsubaki J, Twigg SM, Walker GE, Oh Y. Insulin-like growth factor-binding protein 3 induces caspase-dependent apoptosis through a death receptor-mediated pathway in MCF-7 human breast cancer cells. Cancer Res,2004,64(6):2229-2237.
6. Norris PS,Haas M. A fluorescent p53GFP fusion protein facilitates its detection in mammalian cells while retaining the properties of wild-type p53. Oncogene, 1997,15(18):2241-2247.
7. Rowan S, Ludwig RL, Haupt Y, Bates S, Lu X, Oren M, Vousden KH. Specific loss of apoptotic but not cell-cycle arrest function in a human tumor derived p53 mutant. EMBO J,1996,15(4):827-838.
8. Ryan KM,Vousden KH. Characterization of structural p53 mutants which show selective defects in apoptosis but not cell cycle arrest. Mol Cell Biol,1998, 18(7):3692-3698.
9. Wahlfors J, Loimas S, Pasanen T, Hakkarainen T. Green fluorescent protein (GFP) fusion constructs in gene therapy research. Hislochem Cell Biol,2001, 115(1):59-65.
10. Wu Y, Mehew JW, Heckman CA, Arcinas M, Boxer I.M. Negative regulation of bcl-2 expression by p53 in hematopoietic cells. Oncogene,2001, 20(2):240-251.
11. Yamanaka Y, Fowlkes JL, Wilson EM, Rosenfeld RG, Oh Y. Characterization of insulin-like growth factor binding protein-3 (IGFBP-3) binding to human breast cancer cells:kinetics of IGFBP-3 binding and identification of receptor binding domain on the IGFBP-3 molecule. Endocrinology,1999,140(3):1319-1328.
12. Yang E,Korsmeyer SJ. Molecular thanatopsis:a discourse on the BCL2 family and cell death. Blood,1996,88(2):386-401.
13. Zou H, Yang R, Hao J, Wang J, Sun C, Fesik SW, Wu JC, Tomaselli KJ, Armstrong RC. Regulation of the Apaf-1/caspase-9 apoptosome by caspase-3 and XIAP. J Biol Chem,2003,278(10):8091-8098.
1. Ashur-Fabian O, Avivi A, Trakhtenbrot L, Adamsky K, Cohen M, Kajakaro G, Joel A, Amariglio N, Nevo E, Rechavi G. Evolution of p53 in hypoxia-stressed Spalax mimics human tumor mutation. Proc Natl Acad Sci U S A,2004, 101(33):12236-12241.
2. Asker C, Wiman KG, Selivanova G. p53-induced apoptosis as a safeguard against cancer. Biochem Biophys Res Commun,1999,265(1):1-6.
3. Avivi A, Ashur-Fabian O, Amariglio N, Nevo E, Rechavi G. p53--a key player in tumoral and evolutionary adaptation:a lesson from the Israeli blind subterranean mole rat. Cell Cycle,2005,4(3):368-372.
4. Baker SJ, Fearon ER, Nigro JM, Hamilton SR, Preisinger AC, Jessup JM, vanTuinen P, Ledbetter DH, Barker DF, Nakamura Y, White R, Vogelstein B. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science,1989,244(4901):217-221.
5. Banin S, Moyal L, Shieh S, Taya Y, Anderson CW, Chessa L, Smorodinsky NJ, Prives C, Reiss Y, Shiloh Y, Ziv Y. Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science,1998,281(5383):1674-1677.
6. Bargonetti J, Manfredi JJ, Chen X, Marshak DR, Prives C. A proteolytic fragment from the central region of p53 has marked sequence-specific DNA-binding activity when generated from wild-type but not from oncogenic mutant p53 protein. Genes Dev,1993,7(12B):2565-2574.
7. Canman CE, Lim DS, Cimprich KA, Taya Y, Tamai K, Sakaguchi K, Appella E, Kastan MB, Siliciano JD. Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science,1998,281 (5383):1677-1679.
8. Chen D, Li M, Luo J, Gu W. Direct interactions between IIIF-1 alpha and Mdm2 modulate p53 function. J Biol Chem,2003,278(16):13595-13598.
9. Cho Y, Gorina S, Jeffrey PD, Pavletich NP. Crystal structure of a p53 tumor suppressor-DNA complex:understanding tumorigenic mutations. Science,1994, 265(5170):346-355.
10. Clore GM, Ernst J, Clubb R, Omichinski JG, Kennedy WM, Sakaguchi K, Appella E, Gronenborn AM. Refined solution structure of the oligomerization domain of the tumour suppressor p53. Nat Struct Biol,1995,2(4):321-333.
11. Davison TS, Yin P, Nie E, Kay C, Arrowsmith CH. Characterization of the oligomerization defects of two p53 mutants found in families with Li-Fraumeni and Li-Fraumeni-like syndrome. Oncogene,1998,17(5):651-656.
12. el-Deiry WS. Regulation of p53 downstream genes. Semin Cancer Biol,1998, 8(5):345-357.
13. Fels DR,Koumenis C. HIF-lalpha and p53:the ODD couple? Trends Biochem Sci,2005,30(8):426-429.
14. Glazko GV, Koonin EV, Rogozin IB. Mutation hotspots in the p53 gene in tumors of different origin:correlation with evolutionary conservation and signs of positive selection. Biochim Biophys Acta,2004,1679(2):95-106.
15. Gu J, Kawai H, Wiederschain D, Yuan ZM. Mechanism of functional inactivation of a Li-Fraumeni syndrome p53 that has a mutation outside of the DNA-binding domain. Cancer Res,2001,61(4):1741-1746.
16. Hammond EM, Mandell DJ, Salim A, Krieg AJ, Johnson TM, Shirazi HA, Attardi LD, Giaccia AJ. Genome-wide analysis of p53 under hypoxic conditions. Mol Cell Biol,2006,26(9):3492-3504.
17. Hansson LO, Friedler A, Freund S, Rudiger S, Fersht AR. Two sequence motifs from HIF-lalpha bind to the DNA-binding site of p53. Proc Natl Acad Sci U S A,2002,99(16):10305-10309.
18. Haupt Y, Maya R, Kazaz A, Oren M. Mdm2 promotes the rapid degradation of p53. Nature,1997,387(6630):296-299.
19. Koumenis C, Alarcon R, Hammond E, Sutphin P, Hoffman W, Murphy M, Derr J, Taya Y, Lowe SW, Kastan M, Giaccia A. Regulation of p53 by hypoxia: dissociation of transcriptional repression and apoptosis from p53-dependent transactivation. Mol Cell Biol,2001,21 (4):1297-1310.
20. Kubbutat MH, Jones SN, Vousden KH. Regulation of p53 stability by Mdm2. Nature,1997,387(6630):299-303.
21. Lane DP,Crawford LV. T antigen is bound to a host protein in SV40-transformed cells. Nature,1979,278(5701):261-263.
22. Latronico AC, Pinto EM, Domenice S, Fragoso MC, Martin RM, Zerbini MC, Lucon AM, Mendonca BB. An inherited mutation outside the highly conserved DNA-binding domain of the p53 tumor suppressor protein in children and adults with sporadic adrenocortical tumors.J Clin Endocrinol Metab,2001, 86(10):4970-4973.
23. Lee S, Elenbaas B, Levine A, Griffith J. p53 and its 14 kDa C-terminal domain recognize primary DNA damage in the form of insertion/deletion mismatches. Cell,1995,81 (7):1013-1020.
24. Miled C, Pontoglio M, Garbay S, Yaniv M, Weitzman JB. A genomic map of p53 binding sites identifies novel p53 targets involved in an apoptotic network. Cancer Res,2005,65(12):5096-5104.
25. Murphy M, Ahn J, Walker KK, Hoffman WH, Evans RM, Levine AJ, George DL. Transcriptional repression by wild-type p53 utilizes histone deacetylases, mediated by interaction with mSin3a. Genes Dev,1999,13(19):2490-2501.
26. Nakamura Y, Ozaki T, Niizuma H, Ohira M, Kamijo T, Nakagawara A. Functional characterization of a new p53 mutant generated by homozygous deletion in a neuroblastoma cell line. Biochem Biophys Res Commun,2007, 354(4):892-898.
27. Nieminen AL, Qanungo S, Schneider EA, Jiang BH. Agani FH. Mdm2 and HIF-1 alpha interaction in tumor cells during hypoxia. J Cell Physiol,2005, 204(2):364-369.
28. Nikinmaa M,Rees BB. Oxygen-dependent gene expression in fishes. Am J Physiol Regul Integr Comp Physiol,2005,288(5):R1079-1090.
29. Pietenpol JA, Tokino T, Thiagalingam S, el-Deiry WS, Kinzler KW, Vogelstein B. Sequence-specific transcriptional activation is essential for growth suppression by p53. Proc Natl Acad Sci USA,1994,91(6):1998-2002.
30. Resnick MA,Inga A. Functional mutants of the sequence-specific transcription factor p53 and implications for master genes of diversity. Proc Natl Acad Sci U SA,2003,100(17):9934-9939.
31. Sakaguchi K, Herrera JE, Saito S, Miki T, Bustin M, Vassilev A, Anderson CW, Appella E. DNA damage activates p53 through a phosphorylation-acetylation cascade. Genes Dev,1998,12(18):2831-2841.
32. Sanchez-Puig N, Veprintsev DB, Fersht AR. Binding of natively unfolded HIF-lalpha ODD domain to p53. Mol Cell,2005,17(1):11-21.
33. Shaulsky G, Goldfinger N, Ben-Ze'ev A, Rotter V. Nuclear accumulation of p53 protein is mediated by several nuclear localization signals and plays a role in tumorigenesis. Mol Cell Biol,1990,10(12):6565-6577.
34. Shieh SY, Ikeda M, Taya Y, Prives C. DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell,1997,91(3):325-334.
35. Stommel JM, Marchenko ND, Jimenez GS, Moll UM, Hope TJ, Wahl GM. A leucine-rich nuclear export signal in the p53 tetramerization domain:regulation of subcellular localization and p53 activity by NES masking. EMBO J,1999, 18(6):1660-1672.
36. Takagi M, Absalon MJ, McLure KG, Kastan MB. Regulation of p53 translation and induction after DNA damage by ribosomal protein L26 and nucleolin. Cell, 2005,123(1):49-63.
37. Thut CJ, Chen JL, Klemm R, Tjian R. p53 transcriptional activation mediated by coactivators TAFII40 and TAFII60. Science,1995,267(5194):100-104.
38. Walker KK,Levine AJ. Identification of a novel p53 functional domain that is necessary for efficient growth suppression. Proc Natl Acad Sci U S A,1996, 93(26):15335-15340.
39. Wang BQ, Kostrub CF, Finkelstein A, Burton ZF. Production of human RAP30 and RAP74 in bacterial cells. Protein Expr Purif,1993,4(3):207-214.
40. Waterman MJ, Stavridi ES, Waterman JL, Halazonetis TD. ATM-dependent activation of p53 involves dephosphorylation and association with 14-3-3 proteins. Nat Genet,1998,19(2):175-178.
41. Woo RA, McLure KG, Lees-Miller SP, Rancourt DE, Lee PW. DNA-dependent protein kinase acts upstream of p53 in response to DNA damage. Nature,1998, 394(6694):700-704.
42. Zagzag D, Zhong H, Scalzitti JM, Laughner E, Simons JW, Semenza GL. Expression of hypoxia-inducible factor 1 alpha in brain tumors:association with angiogenesis, invasion, and progression. Cancer,2000,88(11):2606-2618.
43. Zhao K, Chai X, Johnston K, Clements A, Marmorstein R. Crystal structure of the mouse p53 core DNA-binding domain at 2.7 A resolution.J Biol Chem, 2001,276(15):12120-12127.
2. Avivi A, Ashur-Fabian O, Amariglio N, Nevo E, Rechavi G. p53-a key player in tumoral and evolutionary adaptation: a lesson from the Israeli blind subterranean mole rat. Cell Cycle,2005,4(3): 368-372.
3. Cai Y, Du JZ. Comparative physiology in China 1984-2007. Comp Biochem Physiol C Toxicol Pharmacol,2008,148(4):296-304.
4. Cao YB, Chen XQ, Wang S, Chen XC, Wang YX, Chang JP, Du JZ. Growth hormone and insulin-like growth factor of naked carp (Gymnocypris przewalskii) in Lake Qinghai:expression in different water environments. Gen Comp Endocrinol,2009,161(3):400-406.
5. Cao YB, Chen XQ, Wang S, Wang YX, Du JZ. Evolution and regulation of the downstream gene of hypoxia-inducible factor-1 alpha in naked carp (Gymnocypris przewalskii) from Lake Qinghai, China. J Mol Evol,2008, 67(5):570-580.
6. Chen XQ, Wang SJ, Du JZ, Chen XC. Diversities in hepatic HIF-1, IGF-I/IGFBP-1, LDH/ICD, and their mRNA expressions induced by CoCl(2) in Qinghai-Tibetan plateau mammals and sea level mice. Am J Physiol Regul Integr Comp Physiol,2007,292(1):R516-526.
7. Du JZ, Li QF, Chen XG. The changing of corticosterone level in native Ochotona curzoniae. Acta Theriologica Sinica,1983,3(1):47-52.
8. Du JZ, Li QF, Chen XG. Effect of Simulated Altitude on liver of Ochotona curzoniae and rats. Acta Zool. Fennica,1984,171:201-203.
9. Du JZ, Wang Y, Brauner C, Richards J, Chen X. "Diversity in a changing environment"-the International Conference of Comparative Physiology, Biochemistry and Toxicology and 6th Chinese Comparative Physiology Conference. Comp Biochem Physiol C Toxicol Pharmacol,2008, 148(4):293-295.
10. Du JZ, Zhou ZQ. Report on the 5th Comparative Physiology Conference of Chinese Association for Physiological Sciences. Comp Biochem Physiol A Physiol 2005,140:257-273.
11. Glazko GV, Koonin EV, Rogozin IB. Mutation hotspots in the p53 gene in tumors of different origin:correlation with evolutionary conservation and signs of positive selection. Biochim Biophys Acta,2004,1679(2):95-106.
12. Hernandez I, Maddison LA, Wei Y, DeMayo F, Petras T, Li B, Gingrich JR, Rosen JM, Greenberg NM. Prostate-specific expression of p53(R172L) differentially regulates p21, Bax, and mdm2 to inhibit prostate cancer progression and prolong survival. Mol Cancer Res,2003,1 (14):1036-1047.
13. Klein G. Cancer, apoptosis, and nonimmune surveillance. Cell Death Differ, 2004,11(1):13-17.
14. Li QF, Chen XG, You ZB, Du JZ. A comparative study on effects of acute hypoxia upon livers of three small mammals. Acta Theriologica Sinica 1987, 7(1):51-57.
15. Li QF, Du JZ. Effect of chronic hypoxia on liver of Ochotona curzoniae and rat. Acta Theriologica Sinica,1986,6(4):261-266.
16. Matey V, Richards JG, Wang Y, Wood CM, Rogers J, Davies R, Murray BW, Chen XQ, Du J, Brauner CJ. The effect of hypoxia on gill morphology and ionoregulatory status in the Lake Qinghai scaleless carp, Gymnocypris przewalskii. J Exp Biol,2008,211(Pt 7):1063-1074.
17. Miled C, Pontoglio M, Garbay S, Yaniv M, Weitzman JB. A genomic map of p53 binding sites identifies novel p53 targets involved in an apoptotic network. Cancer Res,2005,65(12):5096-5104.
18. O'Bryan DM, Xie Z, Wang Y, Du J, Brauner CJ, Richards JG, Wood CM, Chen XQ, Murray BW. Phylogeography and conservation genetics of Lake Qinghai scaleless carp Gymnocypris przewalskii. J Fish Biol,2010,77(9):2072-2092.
19. Pietenpol JA, Tokino T, Thiagalingam S, el-Deiry WS, Kinzler KW, Vogelstein B. Sequence-specific transcriptional activation is essential for growth suppression by p53. Proc Natl Acad Sci USA,1994,91(6):1998-2002.
20. Soussi T, Caron de Fromentel C, May P. Structural aspects of the p53 protein in relation to gene evolution. Oncogene,1990,5(7):945-952.
21. Soussi T, May P. Structural aspects of the p53 protein in relation to gene evolution:a second look. JMol Biol,1996,260(5):623-637.
22. Wei DB, Wei L, Zhang JM, Yu HY. Blood-gas properties of plateau zokor (Myospalax baileyi). Comp Biochem Physiol A Mol Integr Physiol,2006, 145(3):372-375.
23. Wood CM, Du J, Rogers J, Brauner CJ, Richards JG, Semple JW, Murray BW, Chen XQ, Wang Y. Przewalski's naked carp (Gymnocypris przewalskii):an endangered species taking a metabolic holiday in Lake Qinghai, China. Physiol Biochem Zool,2007,80(1):59-77.
24. Zhao Y, Chen XQ, Du JZ. Cellular adaptation to hypoxia and p53 transcription regulation. J Zhejiang Univ Sci B,2009,10(5):404-410.
25. 吕永达,霍仲厚.(2005)特殊环境生理学(军事医学科学院出版社).
1. Appella E,Anderson CW. Post-translational modifications and activation of p53 by genotoxic stresses. Eur J Biochem,2001,268(10):2764-2772.
2. Arnold K, Bordoli L, Kopp J, Schwede T. The SWISS-MODEL workspace:a web-based environment for protein structure homology modelling. Bioinformatics,2006,22(2):195-201.
3. Ashur-Fabian O, Avivi A, Trakhtenbrot L, Adamsky K, Cohen M, Kajakaro G, Joel A, Amariglio N, Nevo E, Rechavi G. Evolution of p53 in hypoxia-stressed Spalax mimics human tumor mutation. Proc Natl Acad Sci U S A,2004, 101 (33):12236-12241.
4. Asker C, Wiman KG, Selivanova G. p53-induced apoptosis as a safeguard against cancer. Biochem Biophys Res Commun,1999,265(1):1-6.
5. Avivi A, Ashur-Fabian O, Amariglio N, Nevo E, Rechavi G. p53--a key player in tumoral and evolutionary adaptation:a lesson from the Israeli blind subterranean mole rat. Cell Cycle,2005,4(3):368-372.
6. Baker SJ, Fearon ER, Nigro JM, Hamilton SR, Preisinger AC, Jessup JM, vanTuinen P, Ledbetter DH, Barker DF, Nakamura Y, White R, Vogelstein B. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science,1989,244(4901):217-221.
7. Bargonetti J, Manfredi JJ, Chen X, Marshak DR, Prives C. A proteolytic fragment from the central region of p53 has marked sequence-specific DNA-binding activity when generated from wild-type but not from oncogenic mutant p53 protein. Genes Dev,1993,7(12B):2565-2574.
8. Brodsky LI, Jacob-Hirsch J, Avivi A, Trakhtenbrot L, Zeligson S, Amariglio N, Paz A, Korol AB, Band M, Rechavi G, Nevo E. Evolutionary regulation of the blind subterranean mole rat, Spalax, revealed by genome-wide gene expression. Proc Natl Acad Sci USA,2005,102(47):17047-17052.
9. Brodsky MH, Nordstrom W, Tsang G, Kwan E, Rubin GM, Abrams JM. Drosophila p53 binds a damage response element at the reaper locus. Cell, 2000,101(1):103-113.
10. Brunhoff C, Galbreath KE, Fedorov VB, Cook JA, Jaarola M. Holarctic phylogeography of the root vole (Microtus oeconomus):implications for late Quaternary biogeography of high latitudes. Mol Ecol,2003,12(4):957-968.
11. Cho Y, Gorina S, Jeffrey PD, Pavletich NP. Crystal structure of a p53 tumor suppressor-DNA complex:understanding tumorigenic mutations. Science,1994, 265(5170):346-355.
12. Clore GM, Ernst J, Clubb R, Omichinski JG, Kennedy WM, Sakaguchi K, Appella E, Gronenborn AM. Refined solution structure of the oligomerization domain of the tumour suppressor p53. Nat Struct Biol,1995,2(4):321-333.
13. Derry WB, Putzke AP, Rothman JH. Caenorhabditis elegans p53:role in apoptosis, meiosis, and stress resistance. Science,2001,294(5542):591-595.
14. el-Deiry WS. Regulation of p53 downstream genes. Semin Cancer Biol,1998, 8(5):345-357.
15. Fleck CC,Carey HV. Modulation of apoptotic pathways in intestinal mucosa during hibernation. Am J Physiol Regul Integr Comp Physiol,2005, 289(2):R586-R595.
16. Glazko GV, Koonin EV, Rogozin IB. Mutation hotspots in the p53 gene in tumors of different origin:correlation with evolutionary conservation and signs of positive selection. Biochim Biophys Acta,2004,1679(2):95-106.
17. Gu W, Shi XL, Roeder RG. Synergistic activation of transcription by CBP and p53. Nature,1997,387(6635):819-823.
18. Guex N,Peitsch MC. SWISS-MODEL and the Swiss-PdbViewer:an environment for comparative protein modeling. Electrophoresis,1997, 18(15):2714-2723.
19. Hammond EM,Giaccia AJ. The role of p53 in hypoxia-induced apoptosis. Biochem Biophys Res Commun,2005,331 (3):718-725.
20. Hammond EM, Mandell DJ, Salim A, Krieg AJ, Johnson TM, Shirazi HA, Attardi LD, Giaccia AJ. Genome-wide analysis of p53 under hypoxic conditions. Mol Cell Biol,2006,26(9):3492-3504.
21. Humphrey W, Dalke A, Schulten K. VMD:visual molecular dynamics. J Mol Graph,1996,14(l):33-38,27-38.
22. Koumenis C, Alarcon R, Hammond E, Sutphin P, Hoffman W, Murphy M, Derr J, Taya Y, Lowe SW, Kastan M, Giaccia A. Regulation of p53 by hypoxia: dissociation of transcriptional repression and apoptosis from p53-dependent transactivation. Mol Cell Biol,2001,21 (4):1297-1310.
23. Kruse JP,Gu W. Modes of p53 regulation. Cell,2009,137(4):609-622.
24. Lane DP,Crawford LV. T antigen is bound to a host protein in SV40-transformed cells. Nature,1979,278(5701):261-263.
25. Lee S, Elenbaas B, Levine A, Griffith J. p53 and its 14 kDa C-terminal domain recognize primary DNA damage in the form of insertion/deletion mismatches. Cell,1995,81(7):1013-1020.
26. Levine AJ. p53, the cellular gatekeeper for growth and division. Cell,1997, 88(3):323-331.
27. Liang SH,Clarke MF. The nuclear import of p53 is determined by the presence of a basic domain and its relative position to the nuclear localization signal. Oncogene,1999,18(12):2163-2166.
28. Miled C, Pontoglio M, Garbay S, Yaniv M, Weitzman JB. A genomic map of p53 binding sites identifies novel p53 targets involved in an apoptotic network. Cancer Res,2005,65(12):5096-5104.
29. Murphy M, Ahn J, Walker KK, Hoffman WH, Evans RM, Levine AJ, George DL. Transcriptional repression by wild-type p53 utilizes histone deacetylases, mediated by interaction with mSin3a. Genes Dev,1999,13(19):2490-2501.
30. Pietenpol JA, Tokino T, Thiagalingam S, el-Deiry WS, Kinzler KW, Vogelstein B. Sequence-specific transcriptional activation is essential for growth suppression by p53. Proc Natl Acad Sci U S A,1994,91 (6):1998-2002.
31. Rau Embry M, Billiard SM, Di Giulio RT. Lack of p53 induction in fish cells by model chemotherapeutics. Oncogene,2006,25(14):2004-2010.
32. Sakaguchi K, Herrera JE, Saito S, Miki T, Bustin M, Vassilev A, Anderson CW, Appella E. DNA damage activates p53 through a phosphorylation-acetylation cascade. Genes Dev,1998,12(18):2831-2841.
33. Schwede T, Kopp J, Guex N, Peitsch MC. SWISS-MODEL:An automated protein homology-modeling server. Nucleic Acids Re.s,2003, 31(13):3381-3385.
34. Shaulsky G, Goldfinger N, Ben-Ze'ev A, Rotter V. Nuclear accumulation of p53 protein is mediated by several nuclear localization signals and plays a role in tumorigenesis. Mol Cell Biol,1990,10(12):6565-6577.
35. Sionov RV,Haupt Y. The cellular response to p53:the decision between life and death. Oncogene,1999,18(45):6145-6157.
36. Soussi T, Caron de Fromentel C, May P. Structural aspects of the p53 protein in relation to gene evolution. Oncogene,1990,5(7):945-952.
37. Soussi T,May P. Structural aspects of the p53 protein in relation to gene evolution:a second look. JMol Biol,1996,260(5):623-637.
38. Stommel JM, Marchenko ND, Jimenez GS, Moll UM, Hope TJ, Wahl GM. A leucine-rich nuclear export signal in the p53 tetramerization domain:regulation of subcellular localization and p53 activity by NES masking. EMBO J,1999, 18(6):1660-1672.
39. Thut CJ, Chen JL, Klemm R, Tjian R. p53 transcriptional activation mediated by coactivators TAFII40 and TAFII60. Science,1995,267(5194):100-104.
40. Villiard E, Brinkmann H, Moiseeva O, Mallette FA, Ferbeyre G, Roy S. Urodele p53 tolerates amino acid changes found in p53 variants linked to human cancer. BMC Evol Biol,2007,7:180.
41. Vousden KH,Prives C. Blinded by the Light:The Growing Complexity of p53. Cell,2009,137(3):413-431.
42. Walker KK,Levine AJ. Identification of a novel p53 functional domain that is necessary for efficient growth suppression. Proc Natl Acad Sci U S A,1996, 93(26):15335-15340.
43. Wang BQ, Kostrub CF, Finkelstein A, Burton ZF. Production of human RAP30 and RAP74 in bacterial cells. Protein Expr Purif,1993,4(3):207-214.
44. Wei DB, Wei L, Zhang JM, Yu HY. Blood-gas properties of plateau zokor (Myospalax baileyi). Comp Biochem Physiol A Mol Integr Physiol,2006, 145(3):372-375.
45. Yang Z. PAML:a program package for phylogenetic analysis by maximum likelihood. Comput Appl Biosci,1997,13(5):555-556.
46. 邴积才，张三亮,郭文辉,强维秀,汪有奎.中华鼢鼠、甘肃鼢鼠发生规律研究.甘肃林业科技2001,26(2)：12-15.
47. 樊乃昌,施银柱.中国鼢鼠(Eospalax)亚属分类研究.兽类学报,1982,2(2)：183-199.
48. 王晓君,魏登邦,魏莲,张建梅,于红妍.高原鼢鼠和高原鼠兔红细胞低氧适应特征.四川动物2008,27(6)：1100-1103.
49. 王玉山,王德华,王祖望.高原鼠兔和根田鼠的最大代谢率.动物学报,2001,47(6)：601-608.
50. 魏登邦,魏莲.高原鼢鼠的红细胞、血红蛋白及肌红蛋白的测定结果.青海大学学报：自然科学版，2001,19(4)：1-2,12.
51. 魏登邦,张建梅,魏莲,于红妍，王晓君.高原鼢鼠对低氧高二氧化碳环境适应的相关血液生理指标的季节变化.动物学报,2006,52(5)：871-877.
1. Alarcon R, Koumenis C, Geyer RK, Maki CG, Giaccia AJ. Hypoxia induces p53 accumulation through MDM2 down-regulation and inhibition of E6-mediated degradation. Cancer Res,1999,59(24):6046-6051.
2. Ashur-Fabian O, Avivi A, Trakhtenbrot L, Adamsky K, Cohen M, Kajakaro G, Joel A, Amariglio N, Nevo E, Rechavi G. Evolution of p53 in hypoxia-stressed Spalax mimics human tumor mutation. Proc Natl Acad Sci U S A,2004, 101(33):12236-12241.
3. Asker C, Wiman KG, Selivanova G. p53-induced apoptosis as a safeguard against cancer. Biochem Biophys Res Commun,1999,265(1):1-6.
4. Avivi A, Ashur-Fabian O, Amariglio N, Nevo E, Rechavi G. p53--a key player in tumoral and evolutionary adaptation:a lesson from the Israeli blind subterranean mole rat. Cell Cycle,2005,4(3):368-372.
5. Bronstein I, Martin CS, Fortin JJ, Olesen CE, Voyta JC. Chemiluminescence: sensitive detection technology for reporter gene assays. Clin Chem,1996, 42(9):1542-1546.
6. Chene P. The role of tetramerization in p53 function. Oncogene,2001, 20(21):2611-2617.
7. Chitayat S,Arrowsmith CH. Four p(53)s in a pod. Nat Struct Mol Biol,2010, 17(4):390-391.
8. Dittmer D, Pati S, Zambetti G, Chu S, Teresky AK, Moore M, Finlay C, Levine AJ. Gain of function mutations in p53. Nat Genet,1993,4(1):42-46.
9. Dyer BW, Ferrer FA, Klinedinst DK, Rodriguez R. A noncommercial dual luciferase enzyme assay system for reporter gene analysis. Anal Biochem,2000, 282(1):158-161.
10. el-Deiry WS. Regulation of p53 downstream genes. Semin Cancer Biol,1998, 8(5):345-357.
11. Hernandez I, Maddison LA, Wei Y, DeMayo F, Petras T, Li B, Gingrich JR, Rosen JM, Greenberg NM. Prostate-specific expression of p53(R172L) differentially regulates p21, Bax, and mdm2 to inhibit prostate cancer progression and prolong survival. Mol Cancer Res,2003,1(14):1036-1047.
12. Hjelmeland AB, Wu Q, Heddleston JM, Choudhary GS, Macswords J, Lathia JD, McLendon R, Lindner D, Sloan A, Rich JN. Acidic stress promotes a glioma stem cell phenotype. Cell Death Differ,2010.
13. Hjelmeland AB, Wu Q, Heddleston JM, Choudhary GS, MacSwords J, Lathia JD, McLendon R, Lindner D, Sloan A, Rich JN. Acidic stress promotes a glioma stem cell phenotype. Cell Death Differ,2011,18(5):829-840.
14. Jorgensen JB,Mustafa T. The effect of hypoxia on carbohydrate metabolism in flounder (Platichthys flesus L.)I. Utilization of glycogen and accumulation of glycolytic end products in various tissues. Comp Biochem Physiol B,1980, 67:243-248.
15. Kallinowski F,Vaupel P. pH distributions in spontaneous and isotransplanted rat tumours. BrJ Cancer,1988,58(3):314-321.
16. Kato S, Han SY, Liu W, Otsuka K, Shibata H, Kanamaru R, Ishioka C. Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis. ProcNatl Acad Sci U S A,2003,100(14):8424-8429.
17. Kazianis S, Gan L, Della Coletta L, Santi B, Morizot DC, Nairn RS. Cloning and comparative sequence analysis of TP53 in Xiphophorus fish hybrid melanoma models. Gene,1998,212(1):31-38.
18. Kimura K, Shinmura K, Hasegawa T, Beppu Y, Yokoyama R, Yokota J. Germline p53 mutation in a patient with multiple primary cancers. Jpn J Clin Oncol,2001,31(7):349-351.
19. Kitayner M, Rozenberg H, Kessler N, Rabinovich D, Shaulov L, Haran TE, Shakked Z. Structural basis of DNA recognition by p53 tetramers. Mol Cell, 2006,22(6):741-753.
20. Kitayner M, Rozenberg H, Rohs R, Suad O, Rabinovich D, Honig B, Shakked Z. Diversity in DNA recognition by p53 revealed by crystal structures with Hoogsteen base pairs. Nat Struct Mol Biol,2010,17(4):423-429.
21. Klein G. Cancer, apoptosis, and nonimmune surveillance. Cell Death Differ, 2004,11(1):13-17.
22. Koumenis C, Alarcon R, Hammond E, Sutphin P, Hoffman W, Murphy M, Derr J, Taya Y, Lowe SW, Kastan M, Giaccia A. Regulation of p53 by hypoxia: dissociation of transcriptional repression and apoptosis from p53-dependent transactivation. Mol Cell Biol,2001.21 (4):1297-1310.
23. Loh SN. The missing zinc:p53 misfolding and cancer. Metallomics,2010, 2(7):442-449.
24. Lundgreen K, Kiilerich P, Tipsmark CK, Madsen SS, Jensen FB. Physiological response in the European flounder (Platichthys flesus) to variable salinity and oxygen conditions. J Comp Physiol B,2008,178(7):909-915.
25. Miled C, Pontoglio M, Garbay S, Yaniv M, Weitzman JB. A genomic map of p53 binding sites identifies novel p53 targets involved in an apoptotic network. Cancer Res,2005,65(12): 5096-5104.
26. Nagaraj NS, Singh OV, Merchant NB. Proteomics:a strategy to understand the novel targets in protein misfolding and cancer therapy. Expert Rev Proteomics, 2010,7(4):613-623.
27. Pan Y, Oprysko PR, Asham AM, Koch CJ, Simon MC. p53 cannot be induced by hypoxia alone but responds to the hypoxic microenvironment. Oncogene, 2004,23(29):4975-4983.
28. Parks SK, Chiche J, Pouyssegur J. pH control mechanisms of tumor survival and growth. J Cell Physiol,2011,226(2):299-308.
29. Reichert M, Steinbach JP, Supra P, Weller M. Modulation of growth and radiochemosensitivity of human malignant glioma cells by acidosis. Cancer, 2002,95(5):1113-1119.
30. Ryan KM,Vousden KH. Characterization of structural p53 mutants which show selective defects in apoptosis but not cell cycle arrest. Mol Cell Biol,1998, 18(7):3692-3698.
31. Scian MJ, Carchman EH, Mohanraj L, Stagliano KE, Anderson MA, Deb D, Crane BM, Kiyono T, Windle B, Deb SP, Deb S. Wild-type p53 and p73 negatively regulate expression of proliferation related genes. Oncogene,2008, 27(18):2583-2593.
32. Tschop K,Engeland K. Cell cycle-dependent transcription of cyclin B2 is influenced by DNA methylation but is independent of methylation in the CDE and CHR elements. FEBS J,2007,274(20):5235-5249.
33. Villiard E, Brinkmann H, Moiseeva O, Mallette FA, Ferbeyre G, Roy S. Urodele p53 tolerates amino acid changes found in p53 variants linked to human cancer. BMC Evol Biol,2007,7:180.
34. 魏登邦,魏莲,张建梅,于红妍,王晓君.地下鼠对洞道环境适应的研究进展.青海大学学报(自然科学版夕,2007,25(5)：54-57.
35. 魏登邦,张建梅,魏莲,于红妍,王晓君.高原鼢鼠对低氧高二氧化碳环境适应的相关血液生理指标的季节变化.动物学报2006,52(5)：871-877.
1. Bratton SB,Salvesen GS. Regulation of the Apaf-l-caspase-9 apoptosome. J Cell Sci,2010,123(Pt 19):3209-3214.
2. Budhram-Mahadeo V, Morris PJ, Smith MD, Midgley CA, Boxer LM, Latchman DS. p53 suppresses the activation of the Bcl-2 promoter by the Brn-3a POU family transcription factor. J Biol Chem,1999, 274(21):15237-15244.
3. Han J, Jogie-Brahim S, Harada A, Oh Y. Insulin-like growth factor-binding protein-3 suppresses tumor growth via activation of caspase-dependent apoptosis and cross-talk with NF-kappaB signaling. Cancer Lett,2011, 307(2):200-210.
4. Ingermann AR, Yang YF, Han J, Mikami A, Garza AE, Mohanraj L, Fan L, Idowu M, Ware JL, Kim HS, Lee DY, Oh Y. Identification of a novel cell death receptor mediating IGFBP-3-induced anti-tumor effects in breast and prostate cancer. J Biol Chem,2010,285(39):30233-30246.
5. Kim HS, Ingermann AR, Tsubaki J, Twigg SM, Walker GE, Oh Y. Insulin-like growth factor-binding protein 3 induces caspase-dependent apoptosis through a death receptor-mediated pathway in MCF-7 human breast cancer cells. Cancer Res,2004,64(6):2229-2237.
6. Norris PS,Haas M. A fluorescent p53GFP fusion protein facilitates its detection in mammalian cells while retaining the properties of wild-type p53. Oncogene, 1997,15(18):2241-2247.
7. Rowan S, Ludwig RL, Haupt Y, Bates S, Lu X, Oren M, Vousden KH. Specific loss of apoptotic but not cell-cycle arrest function in a human tumor derived p53 mutant. EMBO J,1996,15(4):827-838.
8. Ryan KM,Vousden KH. Characterization of structural p53 mutants which show selective defects in apoptosis but not cell cycle arrest. Mol Cell Biol,1998, 18(7):3692-3698.
9. Wahlfors J, Loimas S, Pasanen T, Hakkarainen T. Green fluorescent protein (GFP) fusion constructs in gene therapy research. Hislochem Cell Biol,2001, 115(1):59-65.
10. Wu Y, Mehew JW, Heckman CA, Arcinas M, Boxer I.M. Negative regulation of bcl-2 expression by p53 in hematopoietic cells. Oncogene,2001, 20(2):240-251.
11. Yamanaka Y, Fowlkes JL, Wilson EM, Rosenfeld RG, Oh Y. Characterization of insulin-like growth factor binding protein-3 (IGFBP-3) binding to human breast cancer cells:kinetics of IGFBP-3 binding and identification of receptor binding domain on the IGFBP-3 molecule. Endocrinology,1999,140(3):1319-1328.
12. Yang E,Korsmeyer SJ. Molecular thanatopsis:a discourse on the BCL2 family and cell death. Blood,1996,88(2):386-401.
13. Zou H, Yang R, Hao J, Wang J, Sun C, Fesik SW, Wu JC, Tomaselli KJ, Armstrong RC. Regulation of the Apaf-1/caspase-9 apoptosome by caspase-3 and XIAP. J Biol Chem,2003,278(10):8091-8098.
1. Ashur-Fabian O, Avivi A, Trakhtenbrot L, Adamsky K, Cohen M, Kajakaro G, Joel A, Amariglio N, Nevo E, Rechavi G. Evolution of p53 in hypoxia-stressed Spalax mimics human tumor mutation. Proc Natl Acad Sci U S A,2004, 101(33):12236-12241.
2. Asker C, Wiman KG, Selivanova G. p53-induced apoptosis as a safeguard against cancer. Biochem Biophys Res Commun,1999,265(1):1-6.
3. Avivi A, Ashur-Fabian O, Amariglio N, Nevo E, Rechavi G. p53--a key player in tumoral and evolutionary adaptation:a lesson from the Israeli blind subterranean mole rat. Cell Cycle,2005,4(3):368-372.
4. Baker SJ, Fearon ER, Nigro JM, Hamilton SR, Preisinger AC, Jessup JM, vanTuinen P, Ledbetter DH, Barker DF, Nakamura Y, White R, Vogelstein B. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science,1989,244(4901):217-221.
5. Banin S, Moyal L, Shieh S, Taya Y, Anderson CW, Chessa L, Smorodinsky NJ, Prives C, Reiss Y, Shiloh Y, Ziv Y. Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science,1998,281(5383):1674-1677.
6. Bargonetti J, Manfredi JJ, Chen X, Marshak DR, Prives C. A proteolytic fragment from the central region of p53 has marked sequence-specific DNA-binding activity when generated from wild-type but not from oncogenic mutant p53 protein. Genes Dev,1993,7(12B):2565-2574.
7. Canman CE, Lim DS, Cimprich KA, Taya Y, Tamai K, Sakaguchi K, Appella E, Kastan MB, Siliciano JD. Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science,1998,281 (5383):1677-1679.
8. Chen D, Li M, Luo J, Gu W. Direct interactions between IIIF-1 alpha and Mdm2 modulate p53 function. J Biol Chem,2003,278(16):13595-13598.
9. Cho Y, Gorina S, Jeffrey PD, Pavletich NP. Crystal structure of a p53 tumor suppressor-DNA complex:understanding tumorigenic mutations. Science,1994, 265(5170):346-355.
10. Clore GM, Ernst J, Clubb R, Omichinski JG, Kennedy WM, Sakaguchi K, Appella E, Gronenborn AM. Refined solution structure of the oligomerization domain of the tumour suppressor p53. Nat Struct Biol,1995,2(4):321-333.
11. Davison TS, Yin P, Nie E, Kay C, Arrowsmith CH. Characterization of the oligomerization defects of two p53 mutants found in families with Li-Fraumeni and Li-Fraumeni-like syndrome. Oncogene,1998,17(5):651-656.
12. el-Deiry WS. Regulation of p53 downstream genes. Semin Cancer Biol,1998, 8(5):345-357.
13. Fels DR,Koumenis C. HIF-lalpha and p53:the ODD couple? Trends Biochem Sci,2005,30(8):426-429.
14. Glazko GV, Koonin EV, Rogozin IB. Mutation hotspots in the p53 gene in tumors of different origin:correlation with evolutionary conservation and signs of positive selection. Biochim Biophys Acta,2004,1679(2):95-106.
15. Gu J, Kawai H, Wiederschain D, Yuan ZM. Mechanism of functional inactivation of a Li-Fraumeni syndrome p53 that has a mutation outside of the DNA-binding domain. Cancer Res,2001,61(4):1741-1746.
16. Hammond EM, Mandell DJ, Salim A, Krieg AJ, Johnson TM, Shirazi HA, Attardi LD, Giaccia AJ. Genome-wide analysis of p53 under hypoxic conditions. Mol Cell Biol,2006,26(9):3492-3504.
17. Hansson LO, Friedler A, Freund S, Rudiger S, Fersht AR. Two sequence motifs from HIF-lalpha bind to the DNA-binding site of p53. Proc Natl Acad Sci U S A,2002,99(16):10305-10309.
18. Haupt Y, Maya R, Kazaz A, Oren M. Mdm2 promotes the rapid degradation of p53. Nature,1997,387(6630):296-299.
19. Koumenis C, Alarcon R, Hammond E, Sutphin P, Hoffman W, Murphy M, Derr J, Taya Y, Lowe SW, Kastan M, Giaccia A. Regulation of p53 by hypoxia: dissociation of transcriptional repression and apoptosis from p53-dependent transactivation. Mol Cell Biol,2001,21 (4):1297-1310.
20. Kubbutat MH, Jones SN, Vousden KH. Regulation of p53 stability by Mdm2. Nature,1997,387(6630):299-303.
21. Lane DP,Crawford LV. T antigen is bound to a host protein in SV40-transformed cells. Nature,1979,278(5701):261-263.
22. Latronico AC, Pinto EM, Domenice S, Fragoso MC, Martin RM, Zerbini MC, Lucon AM, Mendonca BB. An inherited mutation outside the highly conserved DNA-binding domain of the p53 tumor suppressor protein in children and adults with sporadic adrenocortical tumors.J Clin Endocrinol Metab,2001, 86(10):4970-4973.
23. Lee S, Elenbaas B, Levine A, Griffith J. p53 and its 14 kDa C-terminal domain recognize primary DNA damage in the form of insertion/deletion mismatches. Cell,1995,81 (7):1013-1020.
24. Miled C, Pontoglio M, Garbay S, Yaniv M, Weitzman JB. A genomic map of p53 binding sites identifies novel p53 targets involved in an apoptotic network. Cancer Res,2005,65(12):5096-5104.
25. Murphy M, Ahn J, Walker KK, Hoffman WH, Evans RM, Levine AJ, George DL. Transcriptional repression by wild-type p53 utilizes histone deacetylases, mediated by interaction with mSin3a. Genes Dev,1999,13(19):2490-2501.
26. Nakamura Y, Ozaki T, Niizuma H, Ohira M, Kamijo T, Nakagawara A. Functional characterization of a new p53 mutant generated by homozygous deletion in a neuroblastoma cell line. Biochem Biophys Res Commun,2007, 354(4):892-898.
27. Nieminen AL, Qanungo S, Schneider EA, Jiang BH. Agani FH. Mdm2 and HIF-1 alpha interaction in tumor cells during hypoxia. J Cell Physiol,2005, 204(2):364-369.
28. Nikinmaa M,Rees BB. Oxygen-dependent gene expression in fishes. Am J Physiol Regul Integr Comp Physiol,2005,288(5):R1079-1090.
29. Pietenpol JA, Tokino T, Thiagalingam S, el-Deiry WS, Kinzler KW, Vogelstein B. Sequence-specific transcriptional activation is essential for growth suppression by p53. Proc Natl Acad Sci USA,1994,91(6):1998-2002.
30. Resnick MA,Inga A. Functional mutants of the sequence-specific transcription factor p53 and implications for master genes of diversity. Proc Natl Acad Sci U SA,2003,100(17):9934-9939.
31. Sakaguchi K, Herrera JE, Saito S, Miki T, Bustin M, Vassilev A, Anderson CW, Appella E. DNA damage activates p53 through a phosphorylation-acetylation cascade. Genes Dev,1998,12(18):2831-2841.
32. Sanchez-Puig N, Veprintsev DB, Fersht AR. Binding of natively unfolded HIF-lalpha ODD domain to p53. Mol Cell,2005,17(1):11-21.
33. Shaulsky G, Goldfinger N, Ben-Ze'ev A, Rotter V. Nuclear accumulation of p53 protein is mediated by several nuclear localization signals and plays a role in tumorigenesis. Mol Cell Biol,1990,10(12):6565-6577.
34. Shieh SY, Ikeda M, Taya Y, Prives C. DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell,1997,91(3):325-334.
35. Stommel JM, Marchenko ND, Jimenez GS, Moll UM, Hope TJ, Wahl GM. A leucine-rich nuclear export signal in the p53 tetramerization domain:regulation of subcellular localization and p53 activity by NES masking. EMBO J,1999, 18(6):1660-1672.
36. Takagi M, Absalon MJ, McLure KG, Kastan MB. Regulation of p53 translation and induction after DNA damage by ribosomal protein L26 and nucleolin. Cell, 2005,123(1):49-63.
37. Thut CJ, Chen JL, Klemm R, Tjian R. p53 transcriptional activation mediated by coactivators TAFII40 and TAFII60. Science,1995,267(5194):100-104.
38. Walker KK,Levine AJ. Identification of a novel p53 functional domain that is necessary for efficient growth suppression. Proc Natl Acad Sci U S A,1996, 93(26):15335-15340.
39. Wang BQ, Kostrub CF, Finkelstein A, Burton ZF. Production of human RAP30 and RAP74 in bacterial cells. Protein Expr Purif,1993,4(3):207-214.
40. Waterman MJ, Stavridi ES, Waterman JL, Halazonetis TD. ATM-dependent activation of p53 involves dephosphorylation and association with 14-3-3 proteins. Nat Genet,1998,19(2):175-178.
41. Woo RA, McLure KG, Lees-Miller SP, Rancourt DE, Lee PW. DNA-dependent protein kinase acts upstream of p53 in response to DNA damage. Nature,1998, 394(6694):700-704.
42. Zagzag D, Zhong H, Scalzitti JM, Laughner E, Simons JW, Semenza GL. Expression of hypoxia-inducible factor 1 alpha in brain tumors:association with angiogenesis, invasion, and progression. Cancer,2000,88(11):2606-2618.
43. Zhao K, Chai X, Johnston K, Clements A, Marmorstein R. Crystal structure of the mouse p53 core DNA-binding domain at 2.7 A resolution.J Biol Chem, 2001,276(15):12120-12127.