Aurora-A — A guardian of poles

被引:0
作者
Tomotoshi Marumoto
Dongwei Zhang
Hideyuki Saya
机构
[1] Graduate School of Medical Sciences,Department of Tumor Genetics and Biology
[2] Kumamoto University,undefined
[3] 1-1-1 Honjo,undefined
来源
Nature Reviews Cancer | 2005年 / 5卷
关键词
D O I
暂无
中图分类号
学科分类号
摘要
Aurora/Ipl1-related kinases are evolutionally conserved serine/threonine kinases that regulate mitotic progression in various organisms. Humans have three classes of Aurora kinases (A, B and C). Aurora-A and -B are ubiquitously expressed and regulate cell-cycle events from G2 to M phase.Aurora-A is localized at centrosome during interphase, translocated to mitotic spindles in early mitotic phase and degraded after metaphase–anaphase transition. Activation of Aurora-A is required for mitotic entry, centrosome maturation, centrosome separation and chromosome alignment, and inactivation is also necessary for exit from mitosis.Human Aurora-A is frequently amplified in various cancers. The levels of Aurora-A mRNA and protein are increased in those tumours and the overexpression of Aurora-A efficiently transforms immortalized rodent fibroblasts, indicating that Aurora-A is an oncoprotein.Aurora-A kinase is activated by interaction with Ajuba and TPX2 during late G2 and mitotic phases, respectively.Overexpression of Aurora-A induces abnormalities in G2 checkpoint and spindle checkpoint and cytokinesis failure. Those abnormalities lead to chromosome instability but are not sufficient for tumorigenesis in animal models. Additional changes such as p53 inactivation and expression of pro-survival proteins might be required for Aurora-A-mediated tumorigenesis.Aurora-kinase inhibition effectively blocks cell growth and induces apoptosis in cancer cells. It might provide a new approach for the treatment of many human malignancies.
引用
收藏
页码:42 / 50
页数:8
相关论文
共 206 条
[1]  
Nigg EA(2001)Mitotic kinases as regulators of cell division and its checkpoints Nature Rev. Mol. Cell Biol. 2 21-32
[2]  
Li X(2004)Direct association with inner centromere protein (INCENP) activates the novel chromosomal passenger protein, Aurora-C J. Biol. Chem. 279 47201-47211
[3]  
Hu HM(2000)Genomic organization, expression, and chromosome localization of a third aurora-related kinase gene, DNA Cell Biol. 19 679-688
[4]  
Chuang CK(1998)A homologue of EMBO J. 17 3052-3065
[5]  
Lee MJ(1998) aurora kinase is oncogenic and amplified in human colorectal cancers Nature Genet. 20 189-193
[6]  
Tseng TC(2000)Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation Clin. Cancer Res. 6 1833-1839
[7]  
Tang TK(2002)Frequent amplification of chromosomal region 20q12-q13 in ovarian cancer Jpn J. Cancer Res. 93 1114-1122
[8]  
Bischoff JR(2004)Differentially regulated genes as putative targets of amplifications at 20q in ovarian cancers Mol. Cancer Ther. 3 451-457
[9]  
Zhou H(1999)The mitotic serine threonine kinase, Aurora-2, is a potential target for drug development in human pancreatic cancer Cancer Res. 59 2041-2044
[10]  
Tanner MM(2000)Centrosomal kinase AIK1 is overexpressed in invasive ductal carcinoma of the breast Jpn J. Cancer Res. 91 1007-1014