Regulation of greatwall kinase by protein stabilization and nuclear localization

Tomomi M. Yamamoto, Ling Wang, Laura A. Fisher, Frank D. Eckerdt, Aimin Peng

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Greatwall (Gwl) functions as an essential mitotic kinase by antagonizing protein phosphatase 2A. In this study we identifi ed Hsp90, Cdc37 and members of the importin a and b families as the major binding partners of Gwl. Both Hsp90/Cdc37 chaperone and importin complexes associated with the N-terminal kinase domain of Gwl, whereas an intact glycine-rich loop at the N-terminus of Gwl was essential for binding of Hsp90/Cdc37 but not importins. We found that Hsp90 inhibition led to destabilization of Gwl, a mechanism that may partially contribute to the emerging role of Hsp90 in cell cycle progression and the anti-proliferative potential of Hsp90 inhibition. Moreover, in agreement with its importin association, Gwl exhibited nuclear localization in interphase Xenopus S3 cells, and dynamic nucleocytoplasmic distribution during mitosis. We identified KR456/457 as the locus of importin binding and the functional NLS of Gwl. Mutation of this site resulted in exclusion of Gwl from the nucleus. Finally, we showed that the Gwl nuclear localization is indispensable for the biochemical function of Gwl in promoting mitotic entry.

Original languageEnglish (US)
Pages (from-to)3565-3575
Number of pages11
JournalCell Cycle
Volume13
Issue number22
DOIs
StatePublished - Nov 15 2014

Fingerprint

Karyopherins
Nuclear Proteins
Protein Kinases
Phosphotransferases
Protein Phosphatase 2
Interphase
Xenopus
Mitosis
Glycine
Cell Cycle
Mutation

Keywords

  • Greatwall kinase
  • Hsp90
  • Importin
  • Mitosis
  • Nuclear localization

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Regulation of greatwall kinase by protein stabilization and nuclear localization. / Yamamoto, Tomomi M.; Wang, Ling; Fisher, Laura A.; Eckerdt, Frank D.; Peng, Aimin.

In: Cell Cycle, Vol. 13, No. 22, 15.11.2014, p. 3565-3575.

Research output: Contribution to journalArticle

Yamamoto, Tomomi M. ; Wang, Ling ; Fisher, Laura A. ; Eckerdt, Frank D. ; Peng, Aimin. / Regulation of greatwall kinase by protein stabilization and nuclear localization. In: Cell Cycle. 2014 ; Vol. 13, No. 22. pp. 3565-3575.
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