Cell cycle-dependent regulation of Greatwall kinase by protein phosphatase 1 and regulatory subunit 3B

Dapeng Ren, Laura A. Fisher, Jing Zhao, Ling Wang, Byron C. Williams, Michael L. Goldberg, Aimin Peng

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Greatwall (Gwl) kinase plays an essential role in the regulation of mitotic entry and progression. Mitotic activation of Gwl requires both cyclin-dependent kinase 1 (CDK1)-dependent phosphorylation and its autophosphorylation at an evolutionarily conserved serine residue near the carboxyl terminus (Ser-883 in Xenopus). In this study we show that Gwl associates with protein phosphatase 1 (PP1), particularly PP1y, which mediates the dephosphorylation of Gwl Ser-883. Consistent with the mitotic activation of Gwl, its association with PP1 is disrupted in mitotic cells and egg extracts. During mitotic exit, PP1-dependent dephosphorylation of Gwl Ser-883 occurs prior to dephosphorylation of other mitotic substrates; replacing endogenous Gwl with a phosphomimetic S883E mutant blocks mitotic exit. Moreover, we identified PP1 regulatory subunit 3B (PPP1R3B) as a targeting subunit that can direct PP1 activity toward Gwl. PPP1R3B bridges PP1 and Gwl association and promotes Gwl Ser-883 dephosphorylation. Consistent with the cell cycle-dependent association of Gwl and PP1, Gwl and PPP1R3B dissociate in M phase. Interestingly, up-regulation of PPP1R3B facilitates mitotic exit and blocks mitotic entry. Thus, our study suggests PPP1R3B as a new cell cycle regulator that functions by governing Gwl dephosphorylation.

Original languageEnglish (US)
Pages (from-to)10026-10034
Number of pages9
JournalJournal of Biological Chemistry
Volume292
Issue number24
DOIs
StatePublished - Jun 16 2017

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Protein Phosphatase 1
Cell Cycle
Phosphotransferases
Cells
Association reactions
Chemical activation
CDC2 Protein Kinase
Phosphorylation
Xenopus
Cell Extracts
Cell Division
Serine
Ovum
Up-Regulation
Substrates

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Cell cycle-dependent regulation of Greatwall kinase by protein phosphatase 1 and regulatory subunit 3B. / Ren, Dapeng; Fisher, Laura A.; Zhao, Jing; Wang, Ling; Williams, Byron C.; Goldberg, Michael L.; Peng, Aimin.

In: Journal of Biological Chemistry, Vol. 292, No. 24, 16.06.2017, p. 10026-10034.

Research output: Contribution to journalArticle

Ren, Dapeng ; Fisher, Laura A. ; Zhao, Jing ; Wang, Ling ; Williams, Byron C. ; Goldberg, Michael L. ; Peng, Aimin. / Cell cycle-dependent regulation of Greatwall kinase by protein phosphatase 1 and regulatory subunit 3B. In: Journal of Biological Chemistry. 2017 ; Vol. 292, No. 24. pp. 10026-10034.
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