Suppression of p160ROCK bypasses cell cycle arrest after Aurora-A/STK15 depletion.
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 G(2)/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 G(2)/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 G(2)/M.
Du
Jian
J
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Hannon
Gregory J
GJ
D017209:Apoptosis / Q000502:physiology; D064096:Aurora Kinase A; D064127:Aurora Kinases; D002453:Cell Cycle / Q000502:physiology*; D002478:Cells, Cultured; D002875:Chromosomes / Q000648:ultrastructure; D005347:Fibroblasts / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D016195:G2 Phase / Q000502:physiology; D020868:Gene Silencing; D042822:Genomic Instability / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008938:Mitosis / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D008941:Spindle Apparatus / Q000648:ultrastructure; D014162:Transfection; D054460:rho-Associated Kinases
D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases