AIP regulates stability of Aurora-A at early mitotic phase coordinately with GSK-3β

K. Fumoto, P. C. Lee, Hideyuki Saya, A. Kikuchi

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Glycogen synthase kinase-3 (GSK-3β) regulates microtubule dynamics and cellular polarity through phosphorylating various microtubule associating proteins and plus-end tracking proteins. Although it was also reported that GSK-3β is inactivated by protein kinase B at the spindle poles, functions and targets of GSK-3β 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-3β. AIP was colocalized with Aurora-A and GSK-3β 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-3β inhibitor reduced the protein level of Aurora-A and this reduction was suppressed by AIP knockdown. AIP was phosphorylated by GSK-3β, and an AIP mutant in which the GSK-3β phosphorylation site was mutated could bind and downregulate Aurora-A more efficiently. These results suggest that GSK-3β modulates the early mitotic Aurora-A level through binding and phosphorylating AIP.

Original languageEnglish
Pages (from-to)4478-4487
Number of pages10
JournalOncogene
Volume27
Issue number32
DOIs
Publication statusPublished - 2008 Jul 24

Fingerprint

Glycogen Synthase Kinase 3
Protein Stability
Proteins
Spindle Poles
Microtubule Proteins
Proto-Oncogene Proteins c-akt
Mutant Proteins
Metaphase
Microtubules
Down-Regulation
Phosphorylation

Keywords

  • AIP
  • Aurora
  • Cell cycle
  • GSK-3β
  • Mitosis

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

AIP regulates stability of Aurora-A at early mitotic phase coordinately with GSK-3β. / Fumoto, K.; Lee, P. C.; Saya, Hideyuki; Kikuchi, A.

In: Oncogene, Vol. 27, No. 32, 24.07.2008, p. 4478-4487.

Research output: Contribution to journalArticle

Fumoto, K. ; Lee, P. C. ; Saya, Hideyuki ; Kikuchi, A. / AIP regulates stability of Aurora-A at early mitotic phase coordinately with GSK-3β. In: Oncogene. 2008 ; Vol. 27, No. 32. pp. 4478-4487.
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