Aurora kinase-A regulates kinetochore/chromatin associated microtubule assembly in human cells.
Microtubule nucleation and formation from the kinetochore/chromatin have been proposed to contribute to bipolar spindle assembly facilitating equal segregation of chromosomes in mitosis. Although two independent pathways involving the small Ran GTPase-TPX2 proteins and the chromosomal passenger complex proteins have been implicated in the formation of microtubules from the kinetochore/chromatin, detailed molecular mechanisms integrating the pathways and regulating the process have not been well elucidated. This study demonstrates that Aurora kinase-A plays a central role in the kinetochore/chromatin associated microtubule assembly in human cells by integrating the two pathways regulating the process. Silencing by siRNA and over expression of a kinase inactive mutant revealed involvement of Aurora-A at two critical steps. These include accumulation of g-tubulin in the vicinity of kinetochore/chromatin to create microtubule nucleation sites as well as INCENP and TPX2 mediated activation of Aurora-A facilitating formation and stabilization of microtubules. The findings provide the first evidence of Aurora-A, in association with INCENP and TPX2, being a key regulator of kinetochore/chromatin associated microtubule formation in human cells.
Katayama
Hiroshi
H
Department of Molecular Pathology, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77504, USA.
Sasai
Kaori
K
Kloc
Malgorzata
M
Brinkley
Bill R
BR
Sen
Subrata
S
D064096:Aurora Kinase A; D064127:Aurora Kinases; D002843:Chromatin / Q000201:enzymology* / Q000648:ultrastructure; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004789:Enzyme Activation; D025461:Feedback, Physiological; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D016547:Kinesins / Q000378:metabolism; D018386:Kinetochores / Q000201:enzymology* / Q000648:ultrastructure; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000201:enzymology* / Q000648:ultrastructure; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D008941:Spindle Apparatus / Q000201:enzymology; D000077022:Survivin; D014404:Tubulin / Q000378:metabolism
C107489:BIRC5 protein, human; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; C083767:INCENP protein, human; D051034:Inhibitor of Apoptosis Proteins; C091489:KIF2C protein, human; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D014404:Tubulin; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D016547:Kinesins