期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:2004
卷号:101
期号:24
页码:8975-8980
DOI:10.1073/pnas.0308484101
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:Alterations in the expression and activity of the centrosomal kinase, Aurora-A/serine/threonine kinase 15 (STK15), affect genomic stability, disrupt the fidelity of centrosome duplication, and induce cellular transformation. Here, we provide evidence that p160ROCK, a Rho-associate serine/threonine kinase, associates with Aurora-A in a protein complex with other STK15-associated factors. Suppression of Aurora-A by small interfering RNA in HeLa cells blocks the ability of centrosomes to organize normal mitotic spindles, induces G2/M cell cycle arrest, and promotes accumulation of tetraploid cells. In many cases, one outcome of such abnormalities is apoptosis. Introduction of a second genetic lesion, suppression of p160ROCK by RNA interference, can rescue abnormal mitotic spindle formation, release the G2/M cell cycle arrest, and alleviate apoptosis, leading to a greater accumulation of aneuploid cells. These results suggest that Aurora-A and p160ROCK act in a common genetic pathway that promotes and monitors progression through G2/M.