AIP regulates stability of Aurora-A at early mitotic phase coordinately with GSK-3beta.
Glycogen synthase kinase-3 (GSK-3beta) regulates microtubule dynamics and cellular polarity through phosphorylating various microtubule associating proteins and plus-end tracking proteins. Although it was also reported that GSK-3beta is inactivated by protein kinase B at the spindle poles, functions and targets of GSK-3beta in the mitotic phase are unknown. Here, we identified Aurora-A-interacting protein (AIP), a negative regulator of Aurora-A, as a binding partner of GSK-3beta. AIP was colocalized with Aurora-A and GSK-3beta to the spindle poles in metaphase, and its depletion in cells stabilized and activated Aurora-A in early mitotic phase and caused mitotic cell arrest. Treatment of the cells with a GSK-3beta inhibitor reduced the protein level of Aurora-A and this reduction was suppressed by AIP knockdown. AIP was phosphorylated by GSK-3beta, and an AIP mutant in which the GSK-3beta phosphorylation site was mutated could bind and downregulate Aurora-A more efficiently. These results suggest that GSK-3beta modulates the early mitotic Aurora-A level through binding and phosphorylating AIP.
Fumoto
K
K
Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Lee
P-C
PC
Saya
H
H
Kikuchi
A
A
D064127:Aurora Kinases; D002460:Cell Line; D004795:Enzyme Stability; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008938:Mitosis; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000378:metabolism*; D011506:Proteins / Q000032:analysis / Q000502:physiology*; D008941:Spindle Apparatus / Q000737:chemistry
D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C103265:aryl hydrocarbon receptor-interacting protein; D064127:Aurora Kinases; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D017346:Protein Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3