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  • 标题:Suppression of p160ROCK bypasses cell cycle arrest after Aurora-A/STK15 depletion
  • 本地全文:下载
  • 作者:Jian Du ; Gregory J. Hannon
  • 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.
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