Aurora激酶生化通路对细胞有丝分裂可塑性的调节作用
摘要
细胞分裂周期是由时空上高度精密调节的蛋白相互作用信号途径所协调的，从而保证子代细胞从母代得到准确的分成两个相同的等分的遗传信息。细胞周期机制在时间与空间上高度协调控制，一旦这些精确调控的丢失则会丧失基因组稳定性和细胞的可塑性，从而增加癌症发生的风险。
激酶信号途径调节有丝分裂纺锤体的动态性与可塑性以确保准确的染色体分离。有丝分裂启动的关键因子是cyclin-dependent kinase，Cdc2。此外，还有三类serine／threonine激酶家族在有丝分裂中起了重要的调节作用：Polo kinases，Aurora kinases，the NIMA-related kinases。在多种癌症中过表达的Aurora激酶家族参与调节中心体成熟，纺锤体组装，染色体分离和胞质分裂。我博士期间的研究工作主要集中在Aurora激酶信号途径对有丝分裂纺锤体动态性与可塑性的功能调节。
在这里，我们首次对在纺锤体可塑性起关键作用的新中心体结合蛋白ATIP3进行鉴定与功能性描述。使用单一识别的抗体，我的免疫荧光结果表明内源性ATIP3在进入分裂期定位在中心体上，胞质分裂时转移到中体上。外源性ATIP3与微管共定位，缺失突变分析表明489-762残基负责ATIP3与微管结合。通过RNA干扰抑制ATIP3的表达会导致严重的有丝分裂差错：多极纺锤体、不正常的中心粒结构、细胞周期阻断、甚至凋亡。生化试验结果显示ATIP3能与Aurora-A在体内体外相互作用，暗示ATIP3的磷酸化调节在双极纺锤体组装和有丝分裂进程起了重要的作用。
Survivin作为一个内层着丝粒蛋白不仅参与调节染色体分离和胞质分裂，还参与抑制细胞凋亡。survivin在很多肿瘤中过表达，揭示了它的抗调亡功能在肿瘤发生中的可能性作用。为了阐明现阶段对有丝分裂纺锤体结合的survivin如何决定细胞命运的模糊认识，我进行了系统的突变分析，结果令人惊奇：survivin在有丝分裂结构上的分布独立于它在细胞命运决定中的规律。另外，这些突变体都具有与Aurora-B结合的能力并且不影响Aurora-B和CENP-E在动点和中体的定位。而过表达survivin促凋亡点突变体的细胞可以顺利完成细胞分裂，但在进入下一个间期时走向凋亡。我们相信survivin在有丝分裂中的调节功能在时间和空间上都与它的抑制细胞凋亡的功能相互独立。
我在对Aurora-B分子功能进行研究时鉴定了一个新的Aurora-B结合蛋白：p53。肿瘤抑制子p53在应对多种细胞胁迫过程中决定细胞生长或死亡中起了重要的作用。我的生化试验表明发现Aurora-B可以磷酸化p53 Ser315位残基。有趣的是，在293T细胞中表达时，非磷酸化突变体p53~(S315A)比模拟磷酸化突变体p53~(S315D)具有更高的稳定性。因此，我的研究首次证明肿瘤抑制子p53在时间与空间上被CDK2，Aurora-A，Aurora-B所调节。
综上所述，我们的研究阐明了Aurora激酶与它们的底物ATIP3、survivin、p53的相互作用规律，为进一步认识Aurora激酶信号通路对细胞有丝分裂纺锤体动态性与可塑性的调节机理提供了新思路。
The cell division cycle is orchestrated by a cascade of spatiotemporal regulated protein interaction, which ensures a faithful segregation of parent genome into two identical copies for equal distribution into two daughter cells. Any perturbation of this highly coordinated temporal and spatial control of cell cycle machinery will lead to a compromised genomic stability and cellular plasticity, which contributes to the tumorigenesis.
Mitosis is driven by kinase cascades that govern mitotic spindle dynamics and plasticity to ensure accurate chromosome segregation. The key switch for the onset of mitosis is the archetypal cyclin-dependent kinase, Cdc2. In addition to the master mitotic kinase Cdc2, there are three protein serine/threonine kinase families, the Polo kinases, Aurora kinases and the NIMA-related kinases. Aurora kinases regulate centrosome maturation, spindle assembly, chromosome segregation and cytokinesis, which overexpress in a variety of tumors. My doctoral project is centered on the functional delineation of Aurora kinase cascade in mitotic spindle dynamics and plasticity.
Here, we present my identification and functional characterization of a novel centrosome-associated protein ATIP3 essential for mitotic spindle plasticity. Using mono-specific antibody, my immunofluorescence microscopic analysis demonstrated that endogenous ATIP3 is localized at centrosome at the onset of mitosis, and relocated to the midbody during cytokinesis, while exogenous ATIP3 localized to MTs. My deletion analysis revealed that the region containing 489-762aa is essential for ATIP3 binding to microtubule. Inhibition of ATIP3 by RNA interference resulted in severe mitotic defects: multi-polar spindles, abnormal centrioles, mitotic delays, and apoptosis. Our biochemical characterization revealed that ATIP3 is a substrate of Aurora-A in vitro and in vivo, indicating the phospho-regulation of ATIP3 plays an important role in the assembly of a bipolar spindle and in orchestration of mitotic progression.
Survivin is an inner centromere protein implicated in cell division and apoptotic decision. Survivin is overexpressed in most solid tumor, raising the possibility of its anti-apoptotic function in tumorigenesis. To clarify the confusion in the literature as to the functional relevance of survivin in cell fate decision when it is associated with the mitotic spindle, I conducted a systemic mutational analysis. To my surprise, its distribution to the mitotic apparatus is independent of its role in cell fate decision. In addition, those survivin mutants bear Aurora-B-binding activity and did not perturb the localization of Aurora-B and CENP-E to either kinetochore of midbody. In addition, cells overexpressing these survivin mutants progressed throughout mitosis completely, and committed apoptosis in the next interphase. We believe that the function of survivin in mitosis is spatio-temporally separated from its role in apoptosis.
My pursuit for molecular function of Aurora-B led to the identification of a novel Aurora-B-binding partner p53. The tumor suppressor p53 plays an important role in the decision of cell growth or death in response to a variety of stimuli. My biochemical characterizeation shows that p53 is phosphorylated by Aurora-B at Ser315. Interestingly, the non-phosphorylatable mutant of p53~(S315A) bears an increased stability compared to that of phosphor-mimicking mutant p53~(S315D) when they were expressed in 293T cells. Thus, my studies provide the first line evidence in which tumor suppressor p53 is regulated by CDK2, Aurora-A and Aurora-B, in a spatial and temporal manner.
Taken together, my studies illustrate functional interplay between Aurora kinases and their cognate substrates such as ATIP3, p53 and survivin, which provide novel insights into a better understanding of Aurora kinase cascade in mitotic spindle dynamics and plasticity.
激酶信号途径调节有丝分裂纺锤体的动态性与可塑性以确保准确的染色体分离。有丝分裂启动的关键因子是cyclin-dependent kinase，Cdc2。此外，还有三类serine／threonine激酶家族在有丝分裂中起了重要的调节作用：Polo kinases，Aurora kinases，the NIMA-related kinases。在多种癌症中过表达的Aurora激酶家族参与调节中心体成熟，纺锤体组装，染色体分离和胞质分裂。我博士期间的研究工作主要集中在Aurora激酶信号途径对有丝分裂纺锤体动态性与可塑性的功能调节。
在这里，我们首次对在纺锤体可塑性起关键作用的新中心体结合蛋白ATIP3进行鉴定与功能性描述。使用单一识别的抗体，我的免疫荧光结果表明内源性ATIP3在进入分裂期定位在中心体上，胞质分裂时转移到中体上。外源性ATIP3与微管共定位，缺失突变分析表明489-762残基负责ATIP3与微管结合。通过RNA干扰抑制ATIP3的表达会导致严重的有丝分裂差错：多极纺锤体、不正常的中心粒结构、细胞周期阻断、甚至凋亡。生化试验结果显示ATIP3能与Aurora-A在体内体外相互作用，暗示ATIP3的磷酸化调节在双极纺锤体组装和有丝分裂进程起了重要的作用。
Survivin作为一个内层着丝粒蛋白不仅参与调节染色体分离和胞质分裂，还参与抑制细胞凋亡。survivin在很多肿瘤中过表达，揭示了它的抗调亡功能在肿瘤发生中的可能性作用。为了阐明现阶段对有丝分裂纺锤体结合的survivin如何决定细胞命运的模糊认识，我进行了系统的突变分析，结果令人惊奇：survivin在有丝分裂结构上的分布独立于它在细胞命运决定中的规律。另外，这些突变体都具有与Aurora-B结合的能力并且不影响Aurora-B和CENP-E在动点和中体的定位。而过表达survivin促凋亡点突变体的细胞可以顺利完成细胞分裂，但在进入下一个间期时走向凋亡。我们相信survivin在有丝分裂中的调节功能在时间和空间上都与它的抑制细胞凋亡的功能相互独立。
我在对Aurora-B分子功能进行研究时鉴定了一个新的Aurora-B结合蛋白：p53。肿瘤抑制子p53在应对多种细胞胁迫过程中决定细胞生长或死亡中起了重要的作用。我的生化试验表明发现Aurora-B可以磷酸化p53 Ser315位残基。有趣的是，在293T细胞中表达时，非磷酸化突变体p53~(S315A)比模拟磷酸化突变体p53~(S315D)具有更高的稳定性。因此，我的研究首次证明肿瘤抑制子p53在时间与空间上被CDK2，Aurora-A，Aurora-B所调节。
综上所述，我们的研究阐明了Aurora激酶与它们的底物ATIP3、survivin、p53的相互作用规律，为进一步认识Aurora激酶信号通路对细胞有丝分裂纺锤体动态性与可塑性的调节机理提供了新思路。
The cell division cycle is orchestrated by a cascade of spatiotemporal regulated protein interaction, which ensures a faithful segregation of parent genome into two identical copies for equal distribution into two daughter cells. Any perturbation of this highly coordinated temporal and spatial control of cell cycle machinery will lead to a compromised genomic stability and cellular plasticity, which contributes to the tumorigenesis.
Mitosis is driven by kinase cascades that govern mitotic spindle dynamics and plasticity to ensure accurate chromosome segregation. The key switch for the onset of mitosis is the archetypal cyclin-dependent kinase, Cdc2. In addition to the master mitotic kinase Cdc2, there are three protein serine/threonine kinase families, the Polo kinases, Aurora kinases and the NIMA-related kinases. Aurora kinases regulate centrosome maturation, spindle assembly, chromosome segregation and cytokinesis, which overexpress in a variety of tumors. My doctoral project is centered on the functional delineation of Aurora kinase cascade in mitotic spindle dynamics and plasticity.
Here, we present my identification and functional characterization of a novel centrosome-associated protein ATIP3 essential for mitotic spindle plasticity. Using mono-specific antibody, my immunofluorescence microscopic analysis demonstrated that endogenous ATIP3 is localized at centrosome at the onset of mitosis, and relocated to the midbody during cytokinesis, while exogenous ATIP3 localized to MTs. My deletion analysis revealed that the region containing 489-762aa is essential for ATIP3 binding to microtubule. Inhibition of ATIP3 by RNA interference resulted in severe mitotic defects: multi-polar spindles, abnormal centrioles, mitotic delays, and apoptosis. Our biochemical characterization revealed that ATIP3 is a substrate of Aurora-A in vitro and in vivo, indicating the phospho-regulation of ATIP3 plays an important role in the assembly of a bipolar spindle and in orchestration of mitotic progression.
Survivin is an inner centromere protein implicated in cell division and apoptotic decision. Survivin is overexpressed in most solid tumor, raising the possibility of its anti-apoptotic function in tumorigenesis. To clarify the confusion in the literature as to the functional relevance of survivin in cell fate decision when it is associated with the mitotic spindle, I conducted a systemic mutational analysis. To my surprise, its distribution to the mitotic apparatus is independent of its role in cell fate decision. In addition, those survivin mutants bear Aurora-B-binding activity and did not perturb the localization of Aurora-B and CENP-E to either kinetochore of midbody. In addition, cells overexpressing these survivin mutants progressed throughout mitosis completely, and committed apoptosis in the next interphase. We believe that the function of survivin in mitosis is spatio-temporally separated from its role in apoptosis.
My pursuit for molecular function of Aurora-B led to the identification of a novel Aurora-B-binding partner p53. The tumor suppressor p53 plays an important role in the decision of cell growth or death in response to a variety of stimuli. My biochemical characterizeation shows that p53 is phosphorylated by Aurora-B at Ser315. Interestingly, the non-phosphorylatable mutant of p53~(S315A) bears an increased stability compared to that of phosphor-mimicking mutant p53~(S315D) when they were expressed in 293T cells. Thus, my studies provide the first line evidence in which tumor suppressor p53 is regulated by CDK2, Aurora-A and Aurora-B, in a spatial and temporal manner.
Taken together, my studies illustrate functional interplay between Aurora kinases and their cognate substrates such as ATIP3, p53 and survivin, which provide novel insights into a better understanding of Aurora kinase cascade in mitotic spindle dynamics and plasticity.
引文
Adams, R. R., A. A. Tavares, et al., (1998). "pavarotti encodes a kinesin-like protein required to organize the central spindle and contractile ring for cytokinesis." Genes Dev 12(10): 1483-94.
Adams, R. R., S. P. Wheatley, et al., (2000). "INCENP binds the Aurora-related kinase AIRK2 and is required to target it to chromosomes, the central spindle and cleavage furrow." Curr Biol 10(17): 1075-8.
Anand, S., S. Penrhyn-Lowe, et al., (2003). "AURORA-A amplification overrides the mitotic spindle assembly checkpoint, inducing resistance to Taxol." Cancer Cell 3(1): 51-62.
Andrews, P. D. (2005). "Aurorakinases: shining lights on the therapeutic horizon?" Oncogene 24(32): 5005-15.
Andrews, P. D., Y. Ovechkina, et al., (2004). "Aurora-B regulates MCAK at the mitotic centromere." Dev Cell 6(2): 253-68.
Araki, K., K. Nozaki, et al., (2004). "High expression of Aurora-B/Auroraand Ipll-like midbody-associated protein (AIM-l) in astrocytomas." J Neuroonco167(1-2): 53-64.
Barros, T. P., K. Kinoshita, et al., (2005). "AuroraA activates D-TACC-Msps complexes exclusively at centrosomes to stabilize centrosomal Microtubules." J Cell Biol 170(7): 1039-46.
Bayliss, R., T. Sardon, et al., (2004). "Determinants for Aurora-A activation and Aurora-B discrimination by TPX2." Cell Cycle 3(4): 404-3.
Bayliss, R., T. Sardon, et al., (2003). "Structural basis of Aurora-A activation by TPX2 at the mitotic spindle." Mol Cell 12(4): 851-62.
Berdnik, D. and J. A. Knoblich (2002). "Drosophila Aurora-A is required for centrosome maturation and actin-dependent asymmetric protein localization during mitosis." Curr Biol 12(8): 640-7.
Bernard, M., P. Sanseau, et al., (1998). "Cloning of STK13, a third human protein kinase related to Drosophila Auroraand budding yeast Ipl1 that maps on chromosome 19q13.3-ter." Genomics 53(3): 406-9.
Bischoff, J. R., L. Anderson, et al., (1998). "A homologue of Drosophila Aurorakinase is oncogenic and amplified in human colorectal cancers." Embo J 17(11): 3052-65.
Bolton, M. A., W. Lan, et al., (2002). "Aurora-B kinase exists in a complex with survivin and INCENP and its kinase activity is stimulated by survivin binding and phosphorylation." Mol Biol Cell 13(9): 3064-37.
Brinkley, B. R. (2001). "Managing the centrosome numbers game: from chaos to stability in cancer cell division." Trends Cell Biol 11 (1): 18-21.
Castro, A., Y. Arlot-Bonnemains, et al., (2002). "APC/Fizzy-Related targets Aurora-A kinase for proteolysis." EMBO Rep 3(5): 457-62.
Castro, A., S. Vigneron, et al., (2002). "The D-Box-activating domain (DAD) is a new proteolysis signal that stimulates the silent D-Box sequence of Aurora-A." EMBO Rep 3(12): 1209-14.
Cazales, M., E. Schmitt, et al., (2005). "CDC25B phosphorylation by Aurora-A occurs at the G2/M transition and is inhibited by DNA damage." Cell Cycle 4(9): 1233-8.
Chan, C. S. and D. Botstein (1993). "Isolation and characterization of chromosome-gain and increase-in-ploidy mutants in yeast." Genetics 135(3): 677-91.
Cheetham, G. M., R. M. Knegtel, et al., (2002). "Crystal structure of Aurora-2, an oncogenic serine/threonine kinase." J Biol Chem 277(45): 42419-22.
Chen, H. L., C. J. Tang, et al., (2005). "Overexpression of an Aurora-C kinase-deficient mutant disrupts the Aurora-B/INCENP complex and induces polyploidy." J Biomed Sci 12(2): 297-310.
Chen, J., S. Jin, et al., (2003). "Survivin enhances Aurora-B kinase activity and localizes Aurora-B in human cells." J Biol Chem 278(1): 486-90.
Chen, S. S., P. C. Chang, et al., (2002). "Suppression of the STK15 oncogenic activity requires a transactivation-independent p53 function." Embo J 21(17): 4491-9.
Clarke, P. R. and C. Zhang (2001). "Ran GTPase: a master regulator of nuclear structure and function during the eukaryotic cell division cycle?" Trends Cell Biol 11(9): 366-71.
Crane, R., A. Kloepfer, et al., (2004). "Requirements for the destruction of human Aurora-A." J Cell Sci 117(Pt 25): 5975-83.
Crosio, C., G M. Fimia, et al., (2002). "Mitotic phosphorylation of histone H3: spatio-temporal regulation by mammalian Aurorakinases." Mol Cell Biol 22(3): 874-45.
Davies, H., G. R. Bignell, et al., (2002). "Mutations of the BRAF gene in human cancer." Nature 417(6892): 949-54.
Ditchfield, C., V. L. Johnson, et al., (2003). "Aurora-B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores." J Cell Biol 161(2): 267-80.
Du, J. and G. J. Hannon (2002). "The centrosomal kinase Aurora-A/STK15 interacts with a putative tumor suppressor NM23-H1." Nucleic Acids Res 30(24): 5465-75.
Du, J. and G J. Hannon (2004). "Suppression of p160ROCK bypasses cell cycle arrest after Aurora-A/STK15 depletion." Proc Natl Acad Sci U S A 101(24): 8975-80.
Ewart-Toland, A., P. Briassouli, et al., (2003). "Identification of Stk6/STK15 as a candidate low-penetrance tumor-susceptibility gene in mouse and human." Nat Genet 34(4): 403-12.
Eyers, P. A., E. Erikson, et al., (2003). "A novel mechanism for activation of the protein kinase AuroraA." Curr Biol 13(8): 691-7.
Eyers, P. A. and J. L. Maller (2004). "Regulation of Xenopus AuroraA activation by TPX2." J Biol Chem 279(10): 9008-15.
Ferrari, S., O. Matin, et al., (2005). "Aurora-A site specificity: a study with synthetic peptide sUbstrates." Biochem J 390(Pt 1): 293-302.
Fischle, W., B. S. Tseng, et al., (2005). "Regulation of HP1-chromatin binding by histone H3 methylation and phosphorylation." Nature 438(7071): 1116-22.
Fujiwara, T., M. Bandi, et al., (2005). "Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells." Nature 437(7061): 1043-7.
Furukawa, T., N. Kanai, et al., (2006). "AURKA is one of the downstream targets of MAPK1/ERK2 in pancreatic cancer." Oncogene 25(35): 4831-9.
Giet, R., D. McLean, et al., (2002). "Drosophila AuroraA kinase is required to localize D-TACC to centrosomes and to regulate astral Microtubules." J Cell Biol 156(3): 437-51.
Giet, R., R. Uzbekov, et al., (1999). "The Xenopus laevis Aurora-related protein kinase pEg2 associates with and phosphorylates the kinesin-related protein XIEg5." J Biol Chem 274(21): 15005-13.
Glotzer, M. (2005). "The molecular requirements for cytokinesis." Science 307(5716): 1735-9.
Glover, D. M., M. H. Leibowitz, et al., (1995). "Mutations in Auroraprevent centrosome separation leading to the formation of monopolar spindles." Cell 81(1): 95-105.
Goepfert, T. M., Y. E. Adigun, et al., (2002). "Centrosome amplification and overexpression of AuroraA are early events in rat mammary carcinogenesis." Cancer Res 62(14): 4115-22.
Goto, H., Y. Yasui, et al., (2002). "Aurora-B phosphorylates Histone H3 at serine28 with regard to the mitotic chromosome condensation." Genes Cells 7(1): 11-7.
Grieco, D,, A. Porcellini, et al., (1996). "Requirement for cAMP-PKA pathway activation by M phase-promoting factor in the transition from mitosis to interphase." Science 271(5256): 1718-23.
Hannak, E., M. Kirkham, et al., (2001). "Aurora-A kinase is required for centrosome maturation in Caenorhabditis elegans." J Cell Biol 155(7): 1109-16.
Harrington, E. A., D. Bebbington, et al., (2004). "VX-680, a potent and selective small-molecule inhibitor of the Aurorakinases, suppresses tumor growth in vivo." Nat Med 10(3): 262-7.
Hata, T., T. Furukawa, et al., (2005). "RNA interference targeting Aurorakinase a suppresses tumor growth and enhances the taxane chemosensitivity in human pancreatic cancer cells." Cancer Res 65(7): 2899-905.
Hauf, S., R. W. Cole, et al., (2003). "The small molecule Hesperadin reveals a role for Aurora-B in correcting kinetochore-Microtubule attachment and in maintaining the spindle assembly checkpoint." J Cell Biol 161(2): 281-94.
Haydon, C. E., P. A. Eyers, et al., (2003). "Identification of novel phosphorylation sites on Xenopus laevis AuroraA and analysis of phosphopeptide enrichment by immobilized metal-affinity chromatography." Mol Cell Proteomics 2(10): 1055-67.
Helps, N. R., X. Luo, et al., (2000). "NIMA-related kinase 2 (Nek2), a cell-cycle-regulated protein kinase localized to centrosomes, is complexed to protein phosphatase 1." Biochem J 349(Pt 2): 509-18.
Hirota, T., N. Kunitoku, et al., (2003). "Aurora-A and an interacting activator, the LIM protein Ajuba, are required for mitotic commitment in human cells." Cell 114(5): 585-98.
Hirota, T., J. J. Lipp, et al., (2005). "Histone H3 serine 10 phosphorylation by Aurora-B causes HP1 dissociation from heterochromatin." Nature 438(7071): 1176-80.
Honda, K., H. Mihara, et al., (2000). "Degradation of human Aurora2 protein kinase by the anaphase-promoting complex-Ubiquitin-proteasome pathway." Oncogene 19(24): 2812-9.
Honda, R., R. Korner, et al., (2003). "Exploring the functional interactions between Aurora-B, INCENP, and survivin in mitosis." Mol Biol Cell 14(8): 3325-41.
Hsu, J. Y., Z. W. Sun, et al., (2000). "Mitotic phosphorylation of histone H3 is governed by Ipl1/Aurorakinase and Glc7/PP1 phosphatase in budding yeast and nematodes." Cell 102(3): 279-91.
Hu, H. M., C. K. Chuang, et al., (2000). "Genomic organization, expression, and chromosome localization of a third Aurora-related kinase gene, Aie1." DNA Cell Biol 19(11): 679-88.
Hutterer, A., D. Berdnik, et al., (2006). "Mitotic activation of the kinase Aurora-A requires its binding partner Bora." Dev Cell 11(2): 147-57.
Jiang, Y., Y. Zhang, et al., (2003). "AuroraA overexpression overrides the mitotic spindle checkpoint triggered by nocodazole, a Microtubule destabilizer." Oncogene 22(51): 8293-301.
Ju, H., H. Cho, et al., (2006). "Functional polymorphism 57Val＞Ile of Aurorakinase A associated with increased risk of gastric cancer progression." Cancer Lett 242(2): 273-9.
Kaitna, S., M. Mendoza, et al., (2000). "Incenp and an Aurora-like kinase form a complex essential for chromosome segregation and efficient completion of cytokinesis." Curr Biol 10(19): 1172-81.
Katayama, H., T. Ota, et al., (1999). "Mitotic kinase expression and colorectal cancer progression." J Natl Cancer Inst 91(13): 1160-2.
Katayama, H., K. Sasai, et al., (2004). "Phosphorylation by Aurorakinase A induces MDM2-mediated destabilization and inhibition of p53." Nat Genet 36(1): 55-62.
Katayama, H., H. Zhou, et al., (2001). "Interaction and feedback regulation between STK15/BTAK/Aurora-A kinase and protein phosphatase 1 through mitotic cell division cycle." J Biol Chem 276(49): 46219-24.
Kawasaki, A., I. Matsumura, et al., (2001). "Downregulation of an AIM-1 kinase couples with megakaryocytic polyploidization of human hematopoietic cells." J Cell Biol 152(2): 275-87.
Keen, N. and S. Taylor (2004). "Aurora-kinase inhibitors as anticancer agents." Nat Rev Cancer 4(12): 927-36.
Kiat, L. S., K. M. Hui, et al., (2002). "Aurora-A kinase interacting protein (AIP), a novel negative regulator of human Aurora-A kinase." J Biol Chem 277(47): 45558-85.
Kimura, M, Y. Matsuda, et al., (1999). "Cell cycle-dependent expression and centrosome localization of a third human Aurora/Ipl1-related protein kinase, AIK3." J Biol Chem 274(11): 7334-40.
Kimura, M. T., T. Mori, et al., (2005). "Two functional coding single nucleotide polymorphisms in STK15 (Aurora-A) coordinately increase esophageal cancer risk." Cancer Res 65(9): 3548-54.
Kinoshita, K., T. L. Noetzel, et al., (2005). "AuroraA phosphorylation of TACC3/maskin is required for centrosome-dependent Microtubule assembly in mitosis." J Cell Biol 170(7): 1047-55.
Koffa, M. D., C. M. Casanova, et al., (2006). "HURP is part of a Ran-dependent complex involved in spindle formation." Curr Biol 16(8): 743-54.
Kramer, E. R., N. Scheuringer, et al., (2000). "Mitotic regulation of the APC activator proteins CDC20 and CDH1." Mol Biol Cell 11(5): 1555-69.
Krystyniak, A., C. Garcia-Echeverria, et al., (2006). "Inhibition of AuroraA in response to DNA damage." Oncogene 25(3): 338-48.
Kufer, T. A., H. H. Sillje, et al., (2002). "Human TPX2 is required for targeting Aurora-A kinase to the spindle." J Cell Biol 158(4): 617-23.
Kunitoku, N., T. Sasayama, et al., (2003). "CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of Aurora-B at inner centromeres and for kinetochore function." Dev Cell 5(6): 853-64.
Kuriyama, R., S. Dragas-Granoic, et al., (1994). "Heterogeneity and Microtubule interaction of the CHO1 antigen, a mitosis-specific kinesin-like protein. Analysis of sUbdomains expressed in insect sf9 cells." J Cell Sci 107 (Pt 12): 3485-99.
Lampson, M. A., K. Renduchitala, et al., (2004). "Correcting improper chromosome-spindle attachments during cell division." Nat Cell Biol 6(3): 232-7.
Lan, W., X. Zhang, et al., (2004). "Aurora-B phosphorylates centromeric MCAK and regulates its localization and Microtubule depolymerization activity." Curr Biol 14(4): 273-86.
Lee, M. J., F. Gergely, et al., (2001). "Msps/XMAP215 interacts with the centrosomal protein D-TACC to regulate Microtubule behaviour." Nat Cell Biol 3(7): 643-9.
Lengauer, C., K. W. Kinzler, et al., (1998). "Genetic instabilities in human cancers." Nature 396(6712): 643-9.
Li, X., G. Sakashita, et al., (2004). "Direct association with inner centromere protein (INCENP) activates the novel chromosomal passenger protein, Aurora-C." J Biol Chem 279(45): 47201-11.
Littlepage, L. E., H. Wu, et al., (2002). "Identification of phosphorylated residues that affect the activity of the mitotic kinase Aurora-A." Proc Natl Acad Sci U S A 99(24): 15440-5.
Liu, Q., S. Kaneko, et al., (2004). "Aurora-A abrogation of p53 DNA binding and transactivation activity by phosphorylation of serine 215." J Biol Chem 279(50): 52175-82.
Marumoto, T., T. Hirota, et al., (2002). "Roles of Aurora-A kinase in mitotic entry and G2 checkpoint in mammalian cells." Genes Cells 7(11): 1173-82.
Marumoto, T., S. Honda, et al., (2003). "Aurora-A kinase maintains the fidelity of early and late mitotic events in HeLa cells." J Biol Chem 278(51): 51786-95.
Mclntosh, J. R., E. L. Grishchuk, et al., (2002). "Chromosome-Microtubule interactions during mitosis." Annu Rev Cell Dev Biol 18: 193-219.
Meraldi, P., R. Honda, et al., (2002). "Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53-/-cells." Embo J 21(4): 483-92.
Meraldi, P. and E. A. Nigg (2002). "The centrosome cycle." FEBS Lett 521(1-3): 9-13.
Mesilaty-Gross, S., A. Reich, et al., (1999). "The Drosophila STAM gene homolog is in a tight gene cluster, and its expression correlates to that of the adjacent gene ial." Gene 231(1-2): 173-86.
Miao, X., T. Sun, et al., (2004). "Functional STK15 Phe31Ile polymorphism is associated with the occurrence and advanced disease status of esophageal squamous cell carcinoma." Cancer Res 64(8): 2680-3.
Mori D, Yano Y, et al., (2007). "NDEL1 phosphorylation bt Aurora-A kinase is essential for centrosomal maturation, separation, and TACC3 recruitment." Mol Cell Biol 27(1): 352-67
Morrow, C. J., A. Tighe, et al., (2005). "Bub1 and Aurora-B cooperate to maintain BubR1-mediated inhibition of APC/CCdc20." J Cell Sci 118(Pt 16): 3639-52.
Nasmyth, K. (2001). "Disseminating the genome: joining, resolving, and separating sister chromatids during mitosis and meiosis." Annu Rev Genet 35: 673-745.
Nasmyth, K. (2002). "Segregating sister genomes: the molecular biology of chromosome separation." Science 297(5581): 559-65.
Neben, K., A. Korshunov, et al., (2004). "Microarray-based screening for molecular markers in medulloblastoma revealed STK15 as independent predictor for survival." Cancer Res 64(9): 3103-11.
Nguyen, H. G., D. Chinnappan, et al., (2005). "Mechanism of Aurora-B degradation and its dependency on intact KEN and A-boxes: identification of an aneuploidy-promoting property." Mol Cell Biol 25(12): 4977-92.
Nigg, E. A. (2001). "Mitotic kinases as regulators of cell division and its checkpoints." Nat Rev Mol Cell Biol 2(1): 21-32.
Nislow, C., V. A. Lombillo, et al., (1992). "A plus-end-directed motor enzyme that moves antiparallel Microtubules in vitro localizes to the interzone of mitotic spindles." Nature 359(6395): 543-7.
Norton, L. and J. Massague (2006). "Is cancer a disease of self-seeding?" Nat Med 12(8): 875-8.
Ohi, R., T. Sapra, et al., (2004). "Differentiation of cytoplasmic and meiotic spindle assembly MCAK functions by Aurora-B-dependent phosphorylation." Mol Biol Cell 15(6): 2895-906.
Ota, T., S. Suto, et al., (2002). "Increased mitotic phosphorylation of histone H3 attributable to AIM-1/Aurora-B overexpression contributes to chromosome number instability." Cancer Res 62(18): 5168-77.
Ouchi, M., N. Fujiuchi, et al., (2004). "BRCA1 phosphorylation by Aurora-A in the regulation of G2 to M transition." J Biol Chem 279(19): 19643-8.
Pinsky, B. A., C. Kung, et al., (2006). "The Ipl1-Auroraprotein kinase activates the spindle checkpoint by creating unattached kinetochores." Nat Cell Biol 8(1): 78-83.
Powers, J., O. Bossinger, et al., (1998). "A nematode kinesin required for cleavage furrow advancement." Curr Biol 8(20): 1133-6.
Pugacheva, E. N. and E. A. Golemis (2005). "The focal adhesion scaffolding protein HEF1 regulates activation of the Aurora-A and Nek2 kinases at the centrosome." Nat Cell Biol 7(10): 937-46.
Raich, W. B., A. N. Moran, et al., (1998). "Cytokinesis and midzone Microtubule organization in Caenorhabditis elegans require the kinesin-like protein ZEN-4." Mol Biol Cell 9(8): 2037-49.
Ried, T., K. Heselmeyer-Haddad, et al., (1999). "Genomic changes defining the genesis, progression, and malignancy potential in solid human tumors: a phenotype/genotype correlation." Genes Chromosomes Cancer 25(3): 195-204.
Roghi, C., R. Giet, et al., (1998). "The Xenopus protein kinase peg2 associates with the centrosome in a cell cycle-dependent manner, binds to the spindle Microtubules and is involved in bipolar mitotic spindle assembly." J Cell Sci 111 (Pt 5): 557-72.
Royce, M. E., W. Xia, et al., (2004). "STK15/Aurora-A expression in primary breast tumors is correlated with nuclear grade but not with prognosis." Cancer 100(1): 12-9.
Sasai, K., H. Katayama, et al., (2004). "Aurora-C kinase is a novel chromosomal passenger protein that can complement Aurora-B kinase function in mitotic cells." Cell Motil Cytoskeleton 59(4): 249-63.
Satinover, D. L., C. A. Leach, et al., (2004). "Activation of Aurora-A kinase by protein phosphatase inhibitor-2, a bifunctional signaling protein." Proc Natl Acad Sci USA 101(23): 8625-30.
Schumacher, J. M., N. Ashcroft, et at., (1998). "A highly conserved centrosomal kinase, AIR-1, is required for accurate cell cycle progression and segregation of developmental factors in Caenorhabditis elegans embryos." Development 125(22): 4391-402.
Schumacher, J. M., A. Golden, et al., (1998). "AIR-2: An Aurora/Ipl1-related protein kinase associated with chromosomes and midbody Microtubules is required for polar body extrusion and cytokinesis in Caenorhabditis elegans embryos." J Cell Biol 143(6): 1635-46.
Sen, S., H. Zhou, et al., (1997). "A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines." Oncogene 14(18): 2195-200.
Sessa, F., M. Mapelli, et al., (2005). "Mechanism of Aurora-B activation by INCENP and inhibition by hesperadin." Mol Cell 18(3): 379-91.
Sillje, H. H., S. Nagel, et al., (2006). "HURP is a Ran-importin beta-regulated protein that stabilizes kinetochore Microtubules in the vicinity of chromosomes." Curr Biol 16(8): 731-42.
Stenoien, D. L., S. Sen, et al., (2003). "Dynamic association of a tumor amplified kinase, Aurora-A, with the centrosome and mitotic spindle." Cell Motil Cytoskeleton 55(2): 134-46.
Taguchi, S., K. Honda, et al., (2002). "Degradation of human Aurora-A protein kinase is mediated by hCdh1." FEBS Lett 519(1-3): 59-65.
Tanaka, T. U. (2002). "Bi-orienting chromosomes on the mitotic spindle." Curr Opin Cell Biol 14(3): 365-71.
Tang, C. J., C. Y. Lin, et al., (2006). "Dynamic localization and functional implications of Aurora-C kinase during male mouse meiosis." Dev Biol 290(2): 398-410.
Tatsuka, M., H. Katayama, et al., (1998). "Multinuclearity and increased ploidy caused by overexpression of the Aurora- and Ipl1-like midbody-associated protein mitotic kinase in human cancer cells." Cancer Res 58(21): 4811-6.
Terada, Y., Y. Uetake, et al., (2003). "Interaction of Aurora-A and centrosomin at the Microtubule-nucleating site in Drosophila and mammalian cells." J Cell Biol 162(5): 757-63.
Tsai, M. Y., C. Wiese, et al., (2003). "A Ran signalling pathway mediated by the mitotic kinase AuroraA in spindle assembly." Nat Cell Biol 5(3): 242-8.
Tsai, M. Y. and Y. Zheng (2005). "AuroraA kinase-coated beads function as Microtubule-organizing centers and enhance RanGTP-induced spindle assembly." Curr Biol 15(23): 2156-63.
Tseng, T. C., S. H. Chen, et al., (1998). "Protein kinase profile of sperm and eggs: cloning and characterization of two novel testis-specific protein kinases (ALE1, ALE2) related to yeast and fly chromosome segregation regulators." DNA Cell Biol 17(10): 823-33.
Uhlmann, F. (2001). "Secured cutting: controlling separase at the metaphase to anaphase transition." EMBO Rep 2(6): 487-92.
Vigneron, S., S. Prieto, et al., (2004). "Kinetochore localization of spindle checkpoint proteins: who controls whom?" Mol Biol Cell 15(10): 4584-96.
Walter, A. O., W. Seghezzi, et al., (2000). "The mitotic serine/threonine kinase Aurora2/AIK is regulated by phosphorylation and degradation." Oncogene 19(42): 4906-16.
Wang, X. X., R. Liu, et al., (2006). "Overexpression of Aurora-A kinase promotes tumor cell proliferation and inhibits apoptosis in esophageal squamous cell carcinoma cell line." Cell Res 16(4): 356-66.
Wei, Y., C. A. Mizzen, et al., (1998). "Phosphorylation of histone H3 at serine 10 is correlated with chromosome condensation during mitosis and meiosis in Tetrahymena." Proc Natl Acad Sci USA 95(13): 7480-4.
Wei, Y., L. Yu, et al., (1999). "Phosphorylation of histone H3 is required for proper chromosome condensation and segregation." Cell 97(1): 99-109.
Wong, J. and G. Fang (2006). "HURP controls spindle dynamics to promote proper interkinetochore tension and efficient kinetochore capture." J Cell Biol 173(6): 879-91.
Wu, J. C., T. Y. Chen, et al., (2005). "Identification of V23RalA-Ser194 as a critical mediator for Aurora-A-induced cellular motility and transformation by small pool expression screening." J Biol Chem 280(10): 9013-22.
Xie, W., L. Li, et al., (1998). "Cell cycle-dependent sUbcellular localization of the TSG101 protein and mitotic and nuclear abnormalities associated with TSG101 deficiency." Proc Natl Acad Sci USA 95(4): 1595-600.
Yanagida, M. (2000). "Cell cycle mechanisms of sister chromatid separation; roles of Cut1/separin and Cut2/securin." Genes Cells 5(1): 1-8.
Yang, H., C. C. Ou, et al., (2004). "Aurora-A kinase regulates telomerase activity through c-Myc in human ovarian and breast epithelial cells." Cancer Res 64(2): 463-7.
Yu, C. T., J. M. Hsu, et al., (2005). "Phosphorylation and stabilization of HURP by Aurora-A: implication of HURP as a transforming target of Aurora-A." Mol Cell Biol 25(14): 5789-800.
Yu, X., K. Minter-Dykhouse, et al., (2005). "Chfr is required for tumor suppression and AuroraA regulation." Nat Genet 37(4): 401-6.
Zeitlin, S. G, R. D. Shelby, et al., (2001). "CENP-A is phosphorylated by Aurora-B kinase and plays an unexpected role in completion of cytokinesis." J Cell Biol 155(7): 1147-57.
Zhang, D., T. Hirota, et al., (2004). "Cre-loxP-controlled periodic Aurora-A overexpression induces mitotic abnormalities and hyperplasia in mammary glands of mouse models." Oncogene 23(54): 8720-30.
Zhao, Z. S., J. P. Lim, et al., (2005). "The GIT-associated kinase PAK targets to the centrosome and regulates Aurora-A." Mol Cell 20(2): 237-49.
Zhou, H., J. Kuang, et al., (1998). "Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation." Nat Genet 20(2): 189-93.
Andrews, P. D. (2005). Aurorakinases: shining lights on the therapeutic horizon? Oncogene 24(32): 5005-15.
Badanoo. J. L., T. M. Teslovich, et al., (2005). The centrosome in human genetic disease. Nat Rev Genet 6(3): 194-205.
Barr, F. A., H. H. Sillje, et al., (2004). Polo-like kinases and the orchestration of cell division. Nat Rev Mol Cell Biol 5(6): 429-40.
Blagden, S. P. and D. M. Glover (2003). Polar expeditions-provisioning the centrosome for mitosis. Nat Cell Biol 5(6): 505-11.
Choi, C., M. H. Kim, et al., (2000). Loss of heterozygosity at chromosome segments 8p22 and 8p11.3-21.1 in transitional-cell carcinoma of the urinary bladder. Int J Cancer 86(4): 501-5.
D'Assoro, A. B., W. L. Lingle, et al., (2002). Centrosome amplification and the development of cancer. Oncogene 21 (40): 6146-53.
Di Benedetto, M., I. Bieche, et al., (2006). Structural organization and expression of human MTUS1, a candidate 8p22 tumor suppressor gene encoding a family of angiotensin Ⅱ AT2 receptor-interacting proteins, ATIP. Gene 380(2): 127-36.
Di Benedetto, M., P. Pineau, et al., (2006). Mutation analysis of the 8p22 candidate tumor suppressor gene ATIP/MTUS1 in hepatocellular carcinoma. Mol Cell Endocrinol 252(1-2): 207-15.
Doxsey, S., D. McCollum, et al., (2005). Centrosomes in cellular regulation. Annu Rev Cell Dev Biol 21: 411-34.
Faragher, A. J. and A. M. Fry (2003). Nek2A kinase stimulates centrosome disjunction and is required for formation of bipolar mitotic spindles. Mol Biol Cell 14(7): 2876-89.
Fukasawa, K. (2005). Centrosome amplification, chromosome instability and cancer development. Cancer Lett 230(1): 6-19.
Gustafson, C. E., P. J. Wilson, et al., (1996). Functional evidence for a colorectal cancer tumor suppressor gene at chromosome 8p23-23 by monochromosome transfer. Cancer Res 56(22): 5238-45.
Marumoto, T., D. Zhang, et al., (2005). Aurora-A-a guardian of poles. Nat Rev Cancer 5(1): 43-50.
Mayer, T. U., T. M. Kapoor, et al., (1999). Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen. Science 286(5441): 971-4.
Nigg, E. A. (2002). Centrosome aberrations: cause or consequence of cancer progression? Nat Rev Cancer 2(11): 815-25.
Nouet, S., N. Amzallag, et al., (2004). Trans-inactivation of receptor tyrosine kinases by novel angiotensin Ⅱ AT2 receptor-interacting protein, ATIP. J Biol Chem 279(28): 28989-97.
Ohi, R., M. L. Coughlin, et al., (2003). An inner centromere protein that stimulates the Microtubule depolymerizing activity of a KinI kinesin. Dev Cell 5(2): 309-21.
Pils, D., P. Horak, et al., (2005). Five genes from chromosomal band 8p22 are significantly down-regulated in ovarian carcinoma: N33 and EFA6R have a potential impact on overall survival. Cancer 104(11): 2417-29.
Saunders, W. (2005). Centrosomal amplification and spindle multipolarity in cancer cells. Semin Cancer Biol 15(1): 25-32.
Seibold, S., C. Rudroff, et al., (2003). Identification of a new tumor suppressor gene located at chromosome 8p21.3-22. Faseb J 17(9): 1180-2.
Wruck, C. J., H. Funke-Kaiser, et al., (2005). Regulation of transport of the angiotensin AT2 receptor by a novel membrane-associated Golgi protein. Arterioscler Thromb Vasc Biol 25(1): 57-64.
Bouck, D. C. and Bloom, K. S. (2005) The kinetochore protein Ndc10p is required for spindle stability and cytokinesis in yeast. Proc Natl Acad Sci U S A. 102: 5408-5413.
Conway, E. M., Pollefeyt, S., Cornelissen, J., DeBaere, I., SteinerMosonyi, M., Ong, K., Baens, M., Collen, D., and Schuh, A. C. (2000). Three differentially expressed survivin eDNA variants encode proteins with distinct antiapoptotic fimctions. Blood 95, 1435-1442.
Deveraux, Q. L., and Reed, J. C. (1999). IAP family proteins-suppressors of apoptosis. Genes Dev. 13, 239-252.
Dohi, T., Beltrami, E., Wall, N. R., Plescia, J., Altieri, D. C. (2004). Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis. J. Clin. Invest. 114: 1117-1127
Eamshaw, W. C. and Bernat, R. L. (1991)Chromosomal passengers: toward an integrated view of mitosis. Chromosoma. 100: 139-146.
Gruneberg, U., et al., (2004) Relocation of Aurora-B from centromeres to the central spindle at the metaphase to anaphase transition requires Mklp2. J. Cell. Biol. 166: 167-172.
Guse, A., et al., (2005) Phosphorylation of ZEN-4/MKLP1 by Aurora-B regulates completion of cytokinesis. Curr Biol. 15: 778-786.
Jones, T.A., Zou, J.Y., and Cowan, S.W., and Kjeldgaard, M. (1991). Improved methods for binding protein models in electron density maps and the location of errors in these models. Acta Crystallogr. A 47, 110-119.
Kobayashi, K., Hatano, M., Otaki, M., Ogasawara, T., and Tokuhisa, T. (1999). Expression of a murine. homoiogue of the inhibitor of apoptosis protein is related to cell proliferation. Proc. Natl. Acad. Sci. USA 96, 1457-1462.
Li, F., Ambrosini, G., Chu, E.Y., Plescia, J., Tognin, S., Marchisio, P.C., and Altieri, D.C. (1998). Control of apoptosis and mitotic spindle checkpoint by survivin. Nature 396, 580-584.
Muchmore, S.W., Chen, J., Jakob, C., Zakula, D., Matayoshi, E.D., Wu, W., Zhang, H., Li, F., Ng. S. C., and Altieri, D.C. (2000). Crystal structure and mutagenic analysis of the inhibitor-of-opoptosis protein survivin. Mol. Cell 6, 173-182.
O'Connor, D.S., Grossman, D., Plescia, J., Li, F., Zhang, H., Villa, A., Tognin, S., Marchisio, P.C., Altieri, D.C., 2000. Regulation of apoptosis at cell division by p34cdc2phosphorylation of survivin. Proc. Natl. Acad. Sci. U.S.A. 97, 13103-131037.
Pereira, G. and Schiebel, E. (2003) Separase regulates INCENP-Aurora-B anaphase spindle function through Cdc14. Science. 302: 2120-2124.
Riedl SJ, Shi Y. (2004). Molecular mechanisms of caspase regulation during apoptosis. Nat Rev Mol Cell Biol. 5: 897-907.
Shi Y. (2002) Mechanisms of caspase activation and inhibition during apoptosis. Mol Cell. 9: 459-470.
Song Z., Yao X., Wu M. (2003) Direct interaction between survivin and Smac/DIABLO is essential for the anti-apoptotic activity of survivin during Taxol-induced apoptosis. J. Biol. Chem. 278, 23130-23140
Tamm, I., Wang, Y., Sausville, E., Scudiero, D.A., Vigna, N., Oltersdorf, T., and Reed, J.C. (1998). IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res. 58, 5315-5320.
Terada, Y., et al., (1998) AIM-1: a mammalian midbody-associated protein required for cytokinesis. EMBO J. 17: 667-676.
Wheatley, S.P., et al., (2001) INCENP is required for proper targeting of survivin to the centromeres and the anaphase spindle during mitosis. Curr Biol. 11: 886-890.
Zeitlin, S.G., et al., (2001)Differential regulation of CENP-A and histone H3 phosphory-lation in G2/M. J Cell Sci. 114: 653-661.
Berger, M., Stahl, N,, Del Sal, G. & Haupt, Y. (2005) Mutations in proline 82 of p53 impAIR its activation by Pin1 and Chk2 in response to DNA damage. Mol. Cell Biol. 25, 5380-5388.
Chipuk, J. E., Bouchier-Hayes, L., Kuwana, T., Newmeyer, D. D. & Green, D. R. (2005) PUMA couples the nuclear and cytoplasmic proapoptotic function of p53. Science 309, 1732-1735.
Craig, A. L. et al., (1999) Novel phosphorylation sites of human tumour suppressor protein p53 at Ser20 and Thr18 that disrupt the binding of MDM2 (mouse doUble minute 2) protein are modified in human cancers. Biochem. J. 342, 133-141.
Dornan, D., Shimizu, H., Burch, L., Smith, A. J. & Hupp, T. R. (2003) The proline repeat domain of p53 binds directly to the transcriptional coactivator p300 and allosterically controls DNA-dependent acetylation of p53. Mol. Cell Biol. 23, 8846-8861.
Green, D. R. & Chipuk, J. E. (2006) p53 and metabolism: inside the TIGAR. Cell 126, 30-32.
Harms, K., Nozell, S. & Chen, X. (2004) The common and distinct target genes of the p53 family transcription factors. Cell. Mol. Life Sci. 61, 822-842.
Honda, R., Tanaka, H. & Yasuda, H. (1997) Oncoprotein MDM2 is a Ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett. 420, 25-27.
Ito, A. et al., (2001) p300/CBP-mediated p53 acetylation is commonly induced by p53-activating agents and inhibited by MDM2. EMBO J. 20, 1331-1340.
Katayama, H., K. Sasai, et al., (2004). "Phosphorylation by Aurorakinase A induces MDM2-mediated destabilization and inhibition of p53." Nat Genet 36(1): 55-62.
Lambert, P. F., Kashanchi, F., Radonovich, M. F., Shiekhattar, R. & Brady, J. N. (1998) Phosphorylation of p53 serine 15 increases interaction with CBP. J. Biol. Chem. 273, 33048-33053.
Laptenko, O. & Prives, C. (2006) Transcriptional regulation by p53: one protein, many possibilities. Cell Death Differ. 13, 951-961.
McKinney, K., Mattia, M., Gottifredi, V. & Prives, C. (2004) p53 linear diffusion along DNA requires its C terminus. Mol. Cell 16, 413-424.
Mihara, M. et al., (2003) p53 has a direct apoptogenic role at the mitochondria. Mol. Cell 11, 577-590.
Oliner, J. D. et al., (1993) Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature 362, 857-860.
Price, B. D., Hughes-Davis, L., and Park, S. J.(1995) Cdk2 kinase phosphorylates serine 315 of human p53 in vitro. Oncogene 11, 73-80.
Stommel, J. M. et al., (1999) A leucine-rich nuclear export signal in the p53 tetramerization domain: regulation of sUbcellular localization and p53 activity by NES masking. EMBO J. 18, 1660-1672.
Walker, K. & Levine, A. (1996) Identification of a novel p53 functional domain that is necessary for efficient growth suppression. Proc. Natl. Acad. Sci. USA 93, 15335-15340.
Weinberg, R. L., Freund, S. M., Veprintsev, D. B., Bycroft, M. & Fersht, A. R. (2004) Regulation of DNA binding of p53 by its C-terminal domain. J. Mol. Biol. 342, 801-811.
Zhang, Y. & Xiong, Y. (2001) A p53 amino-terminal nuclear export signal inhibited by DNA damage-induced phosphorylation. Science 292, 1910-1915.
Adams, R. R., S. P. Wheatley, et al., (2000). "INCENP binds the Aurora-related kinase AIRK2 and is required to target it to chromosomes, the central spindle and cleavage furrow." Curr Biol 10(17): 1075-8.
Anand, S., S. Penrhyn-Lowe, et al., (2003). "AURORA-A amplification overrides the mitotic spindle assembly checkpoint, inducing resistance to Taxol." Cancer Cell 3(1): 51-62.
Andrews, P. D. (2005). "Aurorakinases: shining lights on the therapeutic horizon?" Oncogene 24(32): 5005-15.
Andrews, P. D., Y. Ovechkina, et al., (2004). "Aurora-B regulates MCAK at the mitotic centromere." Dev Cell 6(2): 253-68.
Araki, K., K. Nozaki, et al., (2004). "High expression of Aurora-B/Auroraand Ipll-like midbody-associated protein (AIM-l) in astrocytomas." J Neuroonco167(1-2): 53-64.
Barros, T. P., K. Kinoshita, et al., (2005). "AuroraA activates D-TACC-Msps complexes exclusively at centrosomes to stabilize centrosomal Microtubules." J Cell Biol 170(7): 1039-46.
Bayliss, R., T. Sardon, et al., (2004). "Determinants for Aurora-A activation and Aurora-B discrimination by TPX2." Cell Cycle 3(4): 404-3.
Bayliss, R., T. Sardon, et al., (2003). "Structural basis of Aurora-A activation by TPX2 at the mitotic spindle." Mol Cell 12(4): 851-62.
Berdnik, D. and J. A. Knoblich (2002). "Drosophila Aurora-A is required for centrosome maturation and actin-dependent asymmetric protein localization during mitosis." Curr Biol 12(8): 640-7.
Bernard, M., P. Sanseau, et al., (1998). "Cloning of STK13, a third human protein kinase related to Drosophila Auroraand budding yeast Ipl1 that maps on chromosome 19q13.3-ter." Genomics 53(3): 406-9.
Bischoff, J. R., L. Anderson, et al., (1998). "A homologue of Drosophila Aurorakinase is oncogenic and amplified in human colorectal cancers." Embo J 17(11): 3052-65.
Bolton, M. A., W. Lan, et al., (2002). "Aurora-B kinase exists in a complex with survivin and INCENP and its kinase activity is stimulated by survivin binding and phosphorylation." Mol Biol Cell 13(9): 3064-37.
Brinkley, B. R. (2001). "Managing the centrosome numbers game: from chaos to stability in cancer cell division." Trends Cell Biol 11 (1): 18-21.
Castro, A., Y. Arlot-Bonnemains, et al., (2002). "APC/Fizzy-Related targets Aurora-A kinase for proteolysis." EMBO Rep 3(5): 457-62.
Castro, A., S. Vigneron, et al., (2002). "The D-Box-activating domain (DAD) is a new proteolysis signal that stimulates the silent D-Box sequence of Aurora-A." EMBO Rep 3(12): 1209-14.
Cazales, M., E. Schmitt, et al., (2005). "CDC25B phosphorylation by Aurora-A occurs at the G2/M transition and is inhibited by DNA damage." Cell Cycle 4(9): 1233-8.
Chan, C. S. and D. Botstein (1993). "Isolation and characterization of chromosome-gain and increase-in-ploidy mutants in yeast." Genetics 135(3): 677-91.
Cheetham, G. M., R. M. Knegtel, et al., (2002). "Crystal structure of Aurora-2, an oncogenic serine/threonine kinase." J Biol Chem 277(45): 42419-22.
Chen, H. L., C. J. Tang, et al., (2005). "Overexpression of an Aurora-C kinase-deficient mutant disrupts the Aurora-B/INCENP complex and induces polyploidy." J Biomed Sci 12(2): 297-310.
Chen, J., S. Jin, et al., (2003). "Survivin enhances Aurora-B kinase activity and localizes Aurora-B in human cells." J Biol Chem 278(1): 486-90.
Chen, S. S., P. C. Chang, et al., (2002). "Suppression of the STK15 oncogenic activity requires a transactivation-independent p53 function." Embo J 21(17): 4491-9.
Clarke, P. R. and C. Zhang (2001). "Ran GTPase: a master regulator of nuclear structure and function during the eukaryotic cell division cycle?" Trends Cell Biol 11(9): 366-71.
Crane, R., A. Kloepfer, et al., (2004). "Requirements for the destruction of human Aurora-A." J Cell Sci 117(Pt 25): 5975-83.
Crosio, C., G M. Fimia, et al., (2002). "Mitotic phosphorylation of histone H3: spatio-temporal regulation by mammalian Aurorakinases." Mol Cell Biol 22(3): 874-45.
Davies, H., G. R. Bignell, et al., (2002). "Mutations of the BRAF gene in human cancer." Nature 417(6892): 949-54.
Ditchfield, C., V. L. Johnson, et al., (2003). "Aurora-B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores." J Cell Biol 161(2): 267-80.
Du, J. and G. J. Hannon (2002). "The centrosomal kinase Aurora-A/STK15 interacts with a putative tumor suppressor NM23-H1." Nucleic Acids Res 30(24): 5465-75.
Du, J. and G J. Hannon (2004). "Suppression of p160ROCK bypasses cell cycle arrest after Aurora-A/STK15 depletion." Proc Natl Acad Sci U S A 101(24): 8975-80.
Ewart-Toland, A., P. Briassouli, et al., (2003). "Identification of Stk6/STK15 as a candidate low-penetrance tumor-susceptibility gene in mouse and human." Nat Genet 34(4): 403-12.
Eyers, P. A., E. Erikson, et al., (2003). "A novel mechanism for activation of the protein kinase AuroraA." Curr Biol 13(8): 691-7.
Eyers, P. A. and J. L. Maller (2004). "Regulation of Xenopus AuroraA activation by TPX2." J Biol Chem 279(10): 9008-15.
Ferrari, S., O. Matin, et al., (2005). "Aurora-A site specificity: a study with synthetic peptide sUbstrates." Biochem J 390(Pt 1): 293-302.
Fischle, W., B. S. Tseng, et al., (2005). "Regulation of HP1-chromatin binding by histone H3 methylation and phosphorylation." Nature 438(7071): 1116-22.
Fujiwara, T., M. Bandi, et al., (2005). "Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells." Nature 437(7061): 1043-7.
Furukawa, T., N. Kanai, et al., (2006). "AURKA is one of the downstream targets of MAPK1/ERK2 in pancreatic cancer." Oncogene 25(35): 4831-9.
Giet, R., D. McLean, et al., (2002). "Drosophila AuroraA kinase is required to localize D-TACC to centrosomes and to regulate astral Microtubules." J Cell Biol 156(3): 437-51.
Giet, R., R. Uzbekov, et al., (1999). "The Xenopus laevis Aurora-related protein kinase pEg2 associates with and phosphorylates the kinesin-related protein XIEg5." J Biol Chem 274(21): 15005-13.
Glotzer, M. (2005). "The molecular requirements for cytokinesis." Science 307(5716): 1735-9.
Glover, D. M., M. H. Leibowitz, et al., (1995). "Mutations in Auroraprevent centrosome separation leading to the formation of monopolar spindles." Cell 81(1): 95-105.
Goepfert, T. M., Y. E. Adigun, et al., (2002). "Centrosome amplification and overexpression of AuroraA are early events in rat mammary carcinogenesis." Cancer Res 62(14): 4115-22.
Goto, H., Y. Yasui, et al., (2002). "Aurora-B phosphorylates Histone H3 at serine28 with regard to the mitotic chromosome condensation." Genes Cells 7(1): 11-7.
Grieco, D,, A. Porcellini, et al., (1996). "Requirement for cAMP-PKA pathway activation by M phase-promoting factor in the transition from mitosis to interphase." Science 271(5256): 1718-23.
Hannak, E., M. Kirkham, et al., (2001). "Aurora-A kinase is required for centrosome maturation in Caenorhabditis elegans." J Cell Biol 155(7): 1109-16.
Harrington, E. A., D. Bebbington, et al., (2004). "VX-680, a potent and selective small-molecule inhibitor of the Aurorakinases, suppresses tumor growth in vivo." Nat Med 10(3): 262-7.
Hata, T., T. Furukawa, et al., (2005). "RNA interference targeting Aurorakinase a suppresses tumor growth and enhances the taxane chemosensitivity in human pancreatic cancer cells." Cancer Res 65(7): 2899-905.
Hauf, S., R. W. Cole, et al., (2003). "The small molecule Hesperadin reveals a role for Aurora-B in correcting kinetochore-Microtubule attachment and in maintaining the spindle assembly checkpoint." J Cell Biol 161(2): 281-94.
Haydon, C. E., P. A. Eyers, et al., (2003). "Identification of novel phosphorylation sites on Xenopus laevis AuroraA and analysis of phosphopeptide enrichment by immobilized metal-affinity chromatography." Mol Cell Proteomics 2(10): 1055-67.
Helps, N. R., X. Luo, et al., (2000). "NIMA-related kinase 2 (Nek2), a cell-cycle-regulated protein kinase localized to centrosomes, is complexed to protein phosphatase 1." Biochem J 349(Pt 2): 509-18.
Hirota, T., N. Kunitoku, et al., (2003). "Aurora-A and an interacting activator, the LIM protein Ajuba, are required for mitotic commitment in human cells." Cell 114(5): 585-98.
Hirota, T., J. J. Lipp, et al., (2005). "Histone H3 serine 10 phosphorylation by Aurora-B causes HP1 dissociation from heterochromatin." Nature 438(7071): 1176-80.
Honda, K., H. Mihara, et al., (2000). "Degradation of human Aurora2 protein kinase by the anaphase-promoting complex-Ubiquitin-proteasome pathway." Oncogene 19(24): 2812-9.
Honda, R., R. Korner, et al., (2003). "Exploring the functional interactions between Aurora-B, INCENP, and survivin in mitosis." Mol Biol Cell 14(8): 3325-41.
Hsu, J. Y., Z. W. Sun, et al., (2000). "Mitotic phosphorylation of histone H3 is governed by Ipl1/Aurorakinase and Glc7/PP1 phosphatase in budding yeast and nematodes." Cell 102(3): 279-91.
Hu, H. M., C. K. Chuang, et al., (2000). "Genomic organization, expression, and chromosome localization of a third Aurora-related kinase gene, Aie1." DNA Cell Biol 19(11): 679-88.
Hutterer, A., D. Berdnik, et al., (2006). "Mitotic activation of the kinase Aurora-A requires its binding partner Bora." Dev Cell 11(2): 147-57.
Jiang, Y., Y. Zhang, et al., (2003). "AuroraA overexpression overrides the mitotic spindle checkpoint triggered by nocodazole, a Microtubule destabilizer." Oncogene 22(51): 8293-301.
Ju, H., H. Cho, et al., (2006). "Functional polymorphism 57Val＞Ile of Aurorakinase A associated with increased risk of gastric cancer progression." Cancer Lett 242(2): 273-9.
Kaitna, S., M. Mendoza, et al., (2000). "Incenp and an Aurora-like kinase form a complex essential for chromosome segregation and efficient completion of cytokinesis." Curr Biol 10(19): 1172-81.
Katayama, H., T. Ota, et al., (1999). "Mitotic kinase expression and colorectal cancer progression." J Natl Cancer Inst 91(13): 1160-2.
Katayama, H., K. Sasai, et al., (2004). "Phosphorylation by Aurorakinase A induces MDM2-mediated destabilization and inhibition of p53." Nat Genet 36(1): 55-62.
Katayama, H., H. Zhou, et al., (2001). "Interaction and feedback regulation between STK15/BTAK/Aurora-A kinase and protein phosphatase 1 through mitotic cell division cycle." J Biol Chem 276(49): 46219-24.
Kawasaki, A., I. Matsumura, et al., (2001). "Downregulation of an AIM-1 kinase couples with megakaryocytic polyploidization of human hematopoietic cells." J Cell Biol 152(2): 275-87.
Keen, N. and S. Taylor (2004). "Aurora-kinase inhibitors as anticancer agents." Nat Rev Cancer 4(12): 927-36.
Kiat, L. S., K. M. Hui, et al., (2002). "Aurora-A kinase interacting protein (AIP), a novel negative regulator of human Aurora-A kinase." J Biol Chem 277(47): 45558-85.
Kimura, M, Y. Matsuda, et al., (1999). "Cell cycle-dependent expression and centrosome localization of a third human Aurora/Ipl1-related protein kinase, AIK3." J Biol Chem 274(11): 7334-40.
Kimura, M. T., T. Mori, et al., (2005). "Two functional coding single nucleotide polymorphisms in STK15 (Aurora-A) coordinately increase esophageal cancer risk." Cancer Res 65(9): 3548-54.
Kinoshita, K., T. L. Noetzel, et al., (2005). "AuroraA phosphorylation of TACC3/maskin is required for centrosome-dependent Microtubule assembly in mitosis." J Cell Biol 170(7): 1047-55.
Koffa, M. D., C. M. Casanova, et al., (2006). "HURP is part of a Ran-dependent complex involved in spindle formation." Curr Biol 16(8): 743-54.
Kramer, E. R., N. Scheuringer, et al., (2000). "Mitotic regulation of the APC activator proteins CDC20 and CDH1." Mol Biol Cell 11(5): 1555-69.
Krystyniak, A., C. Garcia-Echeverria, et al., (2006). "Inhibition of AuroraA in response to DNA damage." Oncogene 25(3): 338-48.
Kufer, T. A., H. H. Sillje, et al., (2002). "Human TPX2 is required for targeting Aurora-A kinase to the spindle." J Cell Biol 158(4): 617-23.
Kunitoku, N., T. Sasayama, et al., (2003). "CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of Aurora-B at inner centromeres and for kinetochore function." Dev Cell 5(6): 853-64.
Kuriyama, R., S. Dragas-Granoic, et al., (1994). "Heterogeneity and Microtubule interaction of the CHO1 antigen, a mitosis-specific kinesin-like protein. Analysis of sUbdomains expressed in insect sf9 cells." J Cell Sci 107 (Pt 12): 3485-99.
Lampson, M. A., K. Renduchitala, et al., (2004). "Correcting improper chromosome-spindle attachments during cell division." Nat Cell Biol 6(3): 232-7.
Lan, W., X. Zhang, et al., (2004). "Aurora-B phosphorylates centromeric MCAK and regulates its localization and Microtubule depolymerization activity." Curr Biol 14(4): 273-86.
Lee, M. J., F. Gergely, et al., (2001). "Msps/XMAP215 interacts with the centrosomal protein D-TACC to regulate Microtubule behaviour." Nat Cell Biol 3(7): 643-9.
Lengauer, C., K. W. Kinzler, et al., (1998). "Genetic instabilities in human cancers." Nature 396(6712): 643-9.
Li, X., G. Sakashita, et al., (2004). "Direct association with inner centromere protein (INCENP) activates the novel chromosomal passenger protein, Aurora-C." J Biol Chem 279(45): 47201-11.
Littlepage, L. E., H. Wu, et al., (2002). "Identification of phosphorylated residues that affect the activity of the mitotic kinase Aurora-A." Proc Natl Acad Sci U S A 99(24): 15440-5.
Liu, Q., S. Kaneko, et al., (2004). "Aurora-A abrogation of p53 DNA binding and transactivation activity by phosphorylation of serine 215." J Biol Chem 279(50): 52175-82.
Marumoto, T., T. Hirota, et al., (2002). "Roles of Aurora-A kinase in mitotic entry and G2 checkpoint in mammalian cells." Genes Cells 7(11): 1173-82.
Marumoto, T., S. Honda, et al., (2003). "Aurora-A kinase maintains the fidelity of early and late mitotic events in HeLa cells." J Biol Chem 278(51): 51786-95.
Mclntosh, J. R., E. L. Grishchuk, et al., (2002). "Chromosome-Microtubule interactions during mitosis." Annu Rev Cell Dev Biol 18: 193-219.
Meraldi, P., R. Honda, et al., (2002). "Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53-/-cells." Embo J 21(4): 483-92.
Meraldi, P. and E. A. Nigg (2002). "The centrosome cycle." FEBS Lett 521(1-3): 9-13.
Mesilaty-Gross, S., A. Reich, et al., (1999). "The Drosophila STAM gene homolog is in a tight gene cluster, and its expression correlates to that of the adjacent gene ial." Gene 231(1-2): 173-86.
Miao, X., T. Sun, et al., (2004). "Functional STK15 Phe31Ile polymorphism is associated with the occurrence and advanced disease status of esophageal squamous cell carcinoma." Cancer Res 64(8): 2680-3.
Mori D, Yano Y, et al., (2007). "NDEL1 phosphorylation bt Aurora-A kinase is essential for centrosomal maturation, separation, and TACC3 recruitment." Mol Cell Biol 27(1): 352-67
Morrow, C. J., A. Tighe, et al., (2005). "Bub1 and Aurora-B cooperate to maintain BubR1-mediated inhibition of APC/CCdc20." J Cell Sci 118(Pt 16): 3639-52.
Nasmyth, K. (2001). "Disseminating the genome: joining, resolving, and separating sister chromatids during mitosis and meiosis." Annu Rev Genet 35: 673-745.
Nasmyth, K. (2002). "Segregating sister genomes: the molecular biology of chromosome separation." Science 297(5581): 559-65.
Neben, K., A. Korshunov, et al., (2004). "Microarray-based screening for molecular markers in medulloblastoma revealed STK15 as independent predictor for survival." Cancer Res 64(9): 3103-11.
Nguyen, H. G., D. Chinnappan, et al., (2005). "Mechanism of Aurora-B degradation and its dependency on intact KEN and A-boxes: identification of an aneuploidy-promoting property." Mol Cell Biol 25(12): 4977-92.
Nigg, E. A. (2001). "Mitotic kinases as regulators of cell division and its checkpoints." Nat Rev Mol Cell Biol 2(1): 21-32.
Nislow, C., V. A. Lombillo, et al., (1992). "A plus-end-directed motor enzyme that moves antiparallel Microtubules in vitro localizes to the interzone of mitotic spindles." Nature 359(6395): 543-7.
Norton, L. and J. Massague (2006). "Is cancer a disease of self-seeding?" Nat Med 12(8): 875-8.
Ohi, R., T. Sapra, et al., (2004). "Differentiation of cytoplasmic and meiotic spindle assembly MCAK functions by Aurora-B-dependent phosphorylation." Mol Biol Cell 15(6): 2895-906.
Ota, T., S. Suto, et al., (2002). "Increased mitotic phosphorylation of histone H3 attributable to AIM-1/Aurora-B overexpression contributes to chromosome number instability." Cancer Res 62(18): 5168-77.
Ouchi, M., N. Fujiuchi, et al., (2004). "BRCA1 phosphorylation by Aurora-A in the regulation of G2 to M transition." J Biol Chem 279(19): 19643-8.
Pinsky, B. A., C. Kung, et al., (2006). "The Ipl1-Auroraprotein kinase activates the spindle checkpoint by creating unattached kinetochores." Nat Cell Biol 8(1): 78-83.
Powers, J., O. Bossinger, et al., (1998). "A nematode kinesin required for cleavage furrow advancement." Curr Biol 8(20): 1133-6.
Pugacheva, E. N. and E. A. Golemis (2005). "The focal adhesion scaffolding protein HEF1 regulates activation of the Aurora-A and Nek2 kinases at the centrosome." Nat Cell Biol 7(10): 937-46.
Raich, W. B., A. N. Moran, et al., (1998). "Cytokinesis and midzone Microtubule organization in Caenorhabditis elegans require the kinesin-like protein ZEN-4." Mol Biol Cell 9(8): 2037-49.
Ried, T., K. Heselmeyer-Haddad, et al., (1999). "Genomic changes defining the genesis, progression, and malignancy potential in solid human tumors: a phenotype/genotype correlation." Genes Chromosomes Cancer 25(3): 195-204.
Roghi, C., R. Giet, et al., (1998). "The Xenopus protein kinase peg2 associates with the centrosome in a cell cycle-dependent manner, binds to the spindle Microtubules and is involved in bipolar mitotic spindle assembly." J Cell Sci 111 (Pt 5): 557-72.
Royce, M. E., W. Xia, et al., (2004). "STK15/Aurora-A expression in primary breast tumors is correlated with nuclear grade but not with prognosis." Cancer 100(1): 12-9.
Sasai, K., H. Katayama, et al., (2004). "Aurora-C kinase is a novel chromosomal passenger protein that can complement Aurora-B kinase function in mitotic cells." Cell Motil Cytoskeleton 59(4): 249-63.
Satinover, D. L., C. A. Leach, et al., (2004). "Activation of Aurora-A kinase by protein phosphatase inhibitor-2, a bifunctional signaling protein." Proc Natl Acad Sci USA 101(23): 8625-30.
Schumacher, J. M., N. Ashcroft, et at., (1998). "A highly conserved centrosomal kinase, AIR-1, is required for accurate cell cycle progression and segregation of developmental factors in Caenorhabditis elegans embryos." Development 125(22): 4391-402.
Schumacher, J. M., A. Golden, et al., (1998). "AIR-2: An Aurora/Ipl1-related protein kinase associated with chromosomes and midbody Microtubules is required for polar body extrusion and cytokinesis in Caenorhabditis elegans embryos." J Cell Biol 143(6): 1635-46.
Sen, S., H. Zhou, et al., (1997). "A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines." Oncogene 14(18): 2195-200.
Sessa, F., M. Mapelli, et al., (2005). "Mechanism of Aurora-B activation by INCENP and inhibition by hesperadin." Mol Cell 18(3): 379-91.
Sillje, H. H., S. Nagel, et al., (2006). "HURP is a Ran-importin beta-regulated protein that stabilizes kinetochore Microtubules in the vicinity of chromosomes." Curr Biol 16(8): 731-42.
Stenoien, D. L., S. Sen, et al., (2003). "Dynamic association of a tumor amplified kinase, Aurora-A, with the centrosome and mitotic spindle." Cell Motil Cytoskeleton 55(2): 134-46.
Taguchi, S., K. Honda, et al., (2002). "Degradation of human Aurora-A protein kinase is mediated by hCdh1." FEBS Lett 519(1-3): 59-65.
Tanaka, T. U. (2002). "Bi-orienting chromosomes on the mitotic spindle." Curr Opin Cell Biol 14(3): 365-71.
Tang, C. J., C. Y. Lin, et al., (2006). "Dynamic localization and functional implications of Aurora-C kinase during male mouse meiosis." Dev Biol 290(2): 398-410.
Tatsuka, M., H. Katayama, et al., (1998). "Multinuclearity and increased ploidy caused by overexpression of the Aurora- and Ipl1-like midbody-associated protein mitotic kinase in human cancer cells." Cancer Res 58(21): 4811-6.
Terada, Y., Y. Uetake, et al., (2003). "Interaction of Aurora-A and centrosomin at the Microtubule-nucleating site in Drosophila and mammalian cells." J Cell Biol 162(5): 757-63.
Tsai, M. Y., C. Wiese, et al., (2003). "A Ran signalling pathway mediated by the mitotic kinase AuroraA in spindle assembly." Nat Cell Biol 5(3): 242-8.
Tsai, M. Y. and Y. Zheng (2005). "AuroraA kinase-coated beads function as Microtubule-organizing centers and enhance RanGTP-induced spindle assembly." Curr Biol 15(23): 2156-63.
Tseng, T. C., S. H. Chen, et al., (1998). "Protein kinase profile of sperm and eggs: cloning and characterization of two novel testis-specific protein kinases (ALE1, ALE2) related to yeast and fly chromosome segregation regulators." DNA Cell Biol 17(10): 823-33.
Uhlmann, F. (2001). "Secured cutting: controlling separase at the metaphase to anaphase transition." EMBO Rep 2(6): 487-92.
Vigneron, S., S. Prieto, et al., (2004). "Kinetochore localization of spindle checkpoint proteins: who controls whom?" Mol Biol Cell 15(10): 4584-96.
Walter, A. O., W. Seghezzi, et al., (2000). "The mitotic serine/threonine kinase Aurora2/AIK is regulated by phosphorylation and degradation." Oncogene 19(42): 4906-16.
Wang, X. X., R. Liu, et al., (2006). "Overexpression of Aurora-A kinase promotes tumor cell proliferation and inhibits apoptosis in esophageal squamous cell carcinoma cell line." Cell Res 16(4): 356-66.
Wei, Y., C. A. Mizzen, et al., (1998). "Phosphorylation of histone H3 at serine 10 is correlated with chromosome condensation during mitosis and meiosis in Tetrahymena." Proc Natl Acad Sci USA 95(13): 7480-4.
Wei, Y., L. Yu, et al., (1999). "Phosphorylation of histone H3 is required for proper chromosome condensation and segregation." Cell 97(1): 99-109.
Wong, J. and G. Fang (2006). "HURP controls spindle dynamics to promote proper interkinetochore tension and efficient kinetochore capture." J Cell Biol 173(6): 879-91.
Wu, J. C., T. Y. Chen, et al., (2005). "Identification of V23RalA-Ser194 as a critical mediator for Aurora-A-induced cellular motility and transformation by small pool expression screening." J Biol Chem 280(10): 9013-22.
Xie, W., L. Li, et al., (1998). "Cell cycle-dependent sUbcellular localization of the TSG101 protein and mitotic and nuclear abnormalities associated with TSG101 deficiency." Proc Natl Acad Sci USA 95(4): 1595-600.
Yanagida, M. (2000). "Cell cycle mechanisms of sister chromatid separation; roles of Cut1/separin and Cut2/securin." Genes Cells 5(1): 1-8.
Yang, H., C. C. Ou, et al., (2004). "Aurora-A kinase regulates telomerase activity through c-Myc in human ovarian and breast epithelial cells." Cancer Res 64(2): 463-7.
Yu, C. T., J. M. Hsu, et al., (2005). "Phosphorylation and stabilization of HURP by Aurora-A: implication of HURP as a transforming target of Aurora-A." Mol Cell Biol 25(14): 5789-800.
Yu, X., K. Minter-Dykhouse, et al., (2005). "Chfr is required for tumor suppression and AuroraA regulation." Nat Genet 37(4): 401-6.
Zeitlin, S. G, R. D. Shelby, et al., (2001). "CENP-A is phosphorylated by Aurora-B kinase and plays an unexpected role in completion of cytokinesis." J Cell Biol 155(7): 1147-57.
Zhang, D., T. Hirota, et al., (2004). "Cre-loxP-controlled periodic Aurora-A overexpression induces mitotic abnormalities and hyperplasia in mammary glands of mouse models." Oncogene 23(54): 8720-30.
Zhao, Z. S., J. P. Lim, et al., (2005). "The GIT-associated kinase PAK targets to the centrosome and regulates Aurora-A." Mol Cell 20(2): 237-49.
Zhou, H., J. Kuang, et al., (1998). "Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation." Nat Genet 20(2): 189-93.
Andrews, P. D. (2005). Aurorakinases: shining lights on the therapeutic horizon? Oncogene 24(32): 5005-15.
Badanoo. J. L., T. M. Teslovich, et al., (2005). The centrosome in human genetic disease. Nat Rev Genet 6(3): 194-205.
Barr, F. A., H. H. Sillje, et al., (2004). Polo-like kinases and the orchestration of cell division. Nat Rev Mol Cell Biol 5(6): 429-40.
Blagden, S. P. and D. M. Glover (2003). Polar expeditions-provisioning the centrosome for mitosis. Nat Cell Biol 5(6): 505-11.
Choi, C., M. H. Kim, et al., (2000). Loss of heterozygosity at chromosome segments 8p22 and 8p11.3-21.1 in transitional-cell carcinoma of the urinary bladder. Int J Cancer 86(4): 501-5.
D'Assoro, A. B., W. L. Lingle, et al., (2002). Centrosome amplification and the development of cancer. Oncogene 21 (40): 6146-53.
Di Benedetto, M., I. Bieche, et al., (2006). Structural organization and expression of human MTUS1, a candidate 8p22 tumor suppressor gene encoding a family of angiotensin Ⅱ AT2 receptor-interacting proteins, ATIP. Gene 380(2): 127-36.
Di Benedetto, M., P. Pineau, et al., (2006). Mutation analysis of the 8p22 candidate tumor suppressor gene ATIP/MTUS1 in hepatocellular carcinoma. Mol Cell Endocrinol 252(1-2): 207-15.
Doxsey, S., D. McCollum, et al., (2005). Centrosomes in cellular regulation. Annu Rev Cell Dev Biol 21: 411-34.
Faragher, A. J. and A. M. Fry (2003). Nek2A kinase stimulates centrosome disjunction and is required for formation of bipolar mitotic spindles. Mol Biol Cell 14(7): 2876-89.
Fukasawa, K. (2005). Centrosome amplification, chromosome instability and cancer development. Cancer Lett 230(1): 6-19.
Gustafson, C. E., P. J. Wilson, et al., (1996). Functional evidence for a colorectal cancer tumor suppressor gene at chromosome 8p23-23 by monochromosome transfer. Cancer Res 56(22): 5238-45.
Marumoto, T., D. Zhang, et al., (2005). Aurora-A-a guardian of poles. Nat Rev Cancer 5(1): 43-50.
Mayer, T. U., T. M. Kapoor, et al., (1999). Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen. Science 286(5441): 971-4.
Nigg, E. A. (2002). Centrosome aberrations: cause or consequence of cancer progression? Nat Rev Cancer 2(11): 815-25.
Nouet, S., N. Amzallag, et al., (2004). Trans-inactivation of receptor tyrosine kinases by novel angiotensin Ⅱ AT2 receptor-interacting protein, ATIP. J Biol Chem 279(28): 28989-97.
Ohi, R., M. L. Coughlin, et al., (2003). An inner centromere protein that stimulates the Microtubule depolymerizing activity of a KinI kinesin. Dev Cell 5(2): 309-21.
Pils, D., P. Horak, et al., (2005). Five genes from chromosomal band 8p22 are significantly down-regulated in ovarian carcinoma: N33 and EFA6R have a potential impact on overall survival. Cancer 104(11): 2417-29.
Saunders, W. (2005). Centrosomal amplification and spindle multipolarity in cancer cells. Semin Cancer Biol 15(1): 25-32.
Seibold, S., C. Rudroff, et al., (2003). Identification of a new tumor suppressor gene located at chromosome 8p21.3-22. Faseb J 17(9): 1180-2.
Wruck, C. J., H. Funke-Kaiser, et al., (2005). Regulation of transport of the angiotensin AT2 receptor by a novel membrane-associated Golgi protein. Arterioscler Thromb Vasc Biol 25(1): 57-64.
Bouck, D. C. and Bloom, K. S. (2005) The kinetochore protein Ndc10p is required for spindle stability and cytokinesis in yeast. Proc Natl Acad Sci U S A. 102: 5408-5413.
Conway, E. M., Pollefeyt, S., Cornelissen, J., DeBaere, I., SteinerMosonyi, M., Ong, K., Baens, M., Collen, D., and Schuh, A. C. (2000). Three differentially expressed survivin eDNA variants encode proteins with distinct antiapoptotic fimctions. Blood 95, 1435-1442.
Deveraux, Q. L., and Reed, J. C. (1999). IAP family proteins-suppressors of apoptosis. Genes Dev. 13, 239-252.
Dohi, T., Beltrami, E., Wall, N. R., Plescia, J., Altieri, D. C. (2004). Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis. J. Clin. Invest. 114: 1117-1127
Eamshaw, W. C. and Bernat, R. L. (1991)Chromosomal passengers: toward an integrated view of mitosis. Chromosoma. 100: 139-146.
Gruneberg, U., et al., (2004) Relocation of Aurora-B from centromeres to the central spindle at the metaphase to anaphase transition requires Mklp2. J. Cell. Biol. 166: 167-172.
Guse, A., et al., (2005) Phosphorylation of ZEN-4/MKLP1 by Aurora-B regulates completion of cytokinesis. Curr Biol. 15: 778-786.
Jones, T.A., Zou, J.Y., and Cowan, S.W., and Kjeldgaard, M. (1991). Improved methods for binding protein models in electron density maps and the location of errors in these models. Acta Crystallogr. A 47, 110-119.
Kobayashi, K., Hatano, M., Otaki, M., Ogasawara, T., and Tokuhisa, T. (1999). Expression of a murine. homoiogue of the inhibitor of apoptosis protein is related to cell proliferation. Proc. Natl. Acad. Sci. USA 96, 1457-1462.
Li, F., Ambrosini, G., Chu, E.Y., Plescia, J., Tognin, S., Marchisio, P.C., and Altieri, D.C. (1998). Control of apoptosis and mitotic spindle checkpoint by survivin. Nature 396, 580-584.
Muchmore, S.W., Chen, J., Jakob, C., Zakula, D., Matayoshi, E.D., Wu, W., Zhang, H., Li, F., Ng. S. C., and Altieri, D.C. (2000). Crystal structure and mutagenic analysis of the inhibitor-of-opoptosis protein survivin. Mol. Cell 6, 173-182.
O'Connor, D.S., Grossman, D., Plescia, J., Li, F., Zhang, H., Villa, A., Tognin, S., Marchisio, P.C., Altieri, D.C., 2000. Regulation of apoptosis at cell division by p34cdc2phosphorylation of survivin. Proc. Natl. Acad. Sci. U.S.A. 97, 13103-131037.
Pereira, G. and Schiebel, E. (2003) Separase regulates INCENP-Aurora-B anaphase spindle function through Cdc14. Science. 302: 2120-2124.
Riedl SJ, Shi Y. (2004). Molecular mechanisms of caspase regulation during apoptosis. Nat Rev Mol Cell Biol. 5: 897-907.
Shi Y. (2002) Mechanisms of caspase activation and inhibition during apoptosis. Mol Cell. 9: 459-470.
Song Z., Yao X., Wu M. (2003) Direct interaction between survivin and Smac/DIABLO is essential for the anti-apoptotic activity of survivin during Taxol-induced apoptosis. J. Biol. Chem. 278, 23130-23140
Tamm, I., Wang, Y., Sausville, E., Scudiero, D.A., Vigna, N., Oltersdorf, T., and Reed, J.C. (1998). IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res. 58, 5315-5320.
Terada, Y., et al., (1998) AIM-1: a mammalian midbody-associated protein required for cytokinesis. EMBO J. 17: 667-676.
Wheatley, S.P., et al., (2001) INCENP is required for proper targeting of survivin to the centromeres and the anaphase spindle during mitosis. Curr Biol. 11: 886-890.
Zeitlin, S.G., et al., (2001)Differential regulation of CENP-A and histone H3 phosphory-lation in G2/M. J Cell Sci. 114: 653-661.
Berger, M., Stahl, N,, Del Sal, G. & Haupt, Y. (2005) Mutations in proline 82 of p53 impAIR its activation by Pin1 and Chk2 in response to DNA damage. Mol. Cell Biol. 25, 5380-5388.
Chipuk, J. E., Bouchier-Hayes, L., Kuwana, T., Newmeyer, D. D. & Green, D. R. (2005) PUMA couples the nuclear and cytoplasmic proapoptotic function of p53. Science 309, 1732-1735.
Craig, A. L. et al., (1999) Novel phosphorylation sites of human tumour suppressor protein p53 at Ser20 and Thr18 that disrupt the binding of MDM2 (mouse doUble minute 2) protein are modified in human cancers. Biochem. J. 342, 133-141.
Dornan, D., Shimizu, H., Burch, L., Smith, A. J. & Hupp, T. R. (2003) The proline repeat domain of p53 binds directly to the transcriptional coactivator p300 and allosterically controls DNA-dependent acetylation of p53. Mol. Cell Biol. 23, 8846-8861.
Green, D. R. & Chipuk, J. E. (2006) p53 and metabolism: inside the TIGAR. Cell 126, 30-32.
Harms, K., Nozell, S. & Chen, X. (2004) The common and distinct target genes of the p53 family transcription factors. Cell. Mol. Life Sci. 61, 822-842.
Honda, R., Tanaka, H. & Yasuda, H. (1997) Oncoprotein MDM2 is a Ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett. 420, 25-27.
Ito, A. et al., (2001) p300/CBP-mediated p53 acetylation is commonly induced by p53-activating agents and inhibited by MDM2. EMBO J. 20, 1331-1340.
Katayama, H., K. Sasai, et al., (2004). "Phosphorylation by Aurorakinase A induces MDM2-mediated destabilization and inhibition of p53." Nat Genet 36(1): 55-62.
Lambert, P. F., Kashanchi, F., Radonovich, M. F., Shiekhattar, R. & Brady, J. N. (1998) Phosphorylation of p53 serine 15 increases interaction with CBP. J. Biol. Chem. 273, 33048-33053.
Laptenko, O. & Prives, C. (2006) Transcriptional regulation by p53: one protein, many possibilities. Cell Death Differ. 13, 951-961.
McKinney, K., Mattia, M., Gottifredi, V. & Prives, C. (2004) p53 linear diffusion along DNA requires its C terminus. Mol. Cell 16, 413-424.
Mihara, M. et al., (2003) p53 has a direct apoptogenic role at the mitochondria. Mol. Cell 11, 577-590.
Oliner, J. D. et al., (1993) Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature 362, 857-860.
Price, B. D., Hughes-Davis, L., and Park, S. J.(1995) Cdk2 kinase phosphorylates serine 315 of human p53 in vitro. Oncogene 11, 73-80.
Stommel, J. M. et al., (1999) A leucine-rich nuclear export signal in the p53 tetramerization domain: regulation of sUbcellular localization and p53 activity by NES masking. EMBO J. 18, 1660-1672.
Walker, K. & Levine, A. (1996) Identification of a novel p53 functional domain that is necessary for efficient growth suppression. Proc. Natl. Acad. Sci. USA 93, 15335-15340.
Weinberg, R. L., Freund, S. M., Veprintsev, D. B., Bycroft, M. & Fersht, A. R. (2004) Regulation of DNA binding of p53 by its C-terminal domain. J. Mol. Biol. 342, 801-811.
Zhang, Y. & Xiong, Y. (2001) A p53 amino-terminal nuclear export signal inhibited by DNA damage-induced phosphorylation. Science 292, 1910-1915.