Regulation of Aurora-A kinase on the mitotic spindle.
The error-free segregation of duplicated chromosomes during cell division is essential for the maintenance of an intact genome. This process is brought about by a highly dynamic bipolar array of microtubules, the mitotic spindle. The formation and function of the mitotic spindle during M-phase of the cell cycle is regulated by protein phosphorylation, involving multiple protein kinases and phosphatases. Prominent among the enzymes implicated in spindle assembly is the serine/threonine-specific protein kinase Aurora-A. In several common human tumors, Aurora-A is overexpressed, and deregulation of this kinase was shown to result in mitotic defects and aneuploidy. Moreover, recent genetic evidence directly links the human Aurora-A gene to cancer susceptibility. Several of the physiological substrates of Aurora-A presumably await identification, but recent studies are beginning to shed light on the regulation of this critical mitotic kinase. Here, we review these findings with particular emphasis on the role of TPX2, a prominent spindle component implicated in a Ran-GTP-mediated spindle assembly pathway.
Kufer
Thomas A
TA
Max Planck Institute for Biochemistry, Department of Cell Biology, Am Klopferspitz 18, 82152 Martinsried, Germany.
Nigg
Erich A
EA
Silljé
Herman H W
HH
D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000378:metabolism*; D020090:Chromosome Segregation / Q000502:physiology*; D005786:Gene Expression Regulation; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D008941:Spindle Apparatus / Q000378:metabolism / Q000502:physiology*; D029867:Xenopus Proteins; D020931:ran GTP-Binding Protein / Q000378:metabolism
D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D029867:Xenopus Proteins; D011494:Protein Kinases; C112134:AURKA protein, Xenopus; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D020931:ran GTP-Binding Protein