Cell cycle-dependent regulation of Greatwall kinase by protein phosphatase 1 and regulatory subunit 3B
© 2017 by The American Society for Biochemistry and Molecular Biology, Inc..
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 PP1γ, 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:292 |
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| Enthalten in: |
The Journal of biological chemistry - 292(2017), 24 vom: 16. Juni, Seite 10026-10034 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ren, Dapeng [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.07.2017 Date Revised 04.12.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1074/jbc.M117.778233 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM271327391 |
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| 245 | 1 | 0 | |a Cell cycle-dependent regulation of Greatwall kinase by protein phosphatase 1 and regulatory subunit 3B |
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| 500 | |a Date Revised 04.12.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2017 by The American Society for Biochemistry and Molecular Biology, Inc. | ||
| 520 | |a 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 PP1γ, 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Xenopus | |
| 650 | 4 | |a cell cycle | |
| 650 | 4 | |a mitosis | |
| 650 | 4 | |a phosphatase | |
| 650 | 4 | |a phosphoprotein phosphatase 1 (PP1) | |
| 650 | 7 | |a Intracellular Signaling Peptides and Proteins |2 NLM | |
| 650 | 7 | |a Protein Subunits |2 NLM | |
| 650 | 7 | |a Recombinant Fusion Proteins |2 NLM | |
| 650 | 7 | |a Recombinant Proteins |2 NLM | |
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| 650 | 7 | |a Protein Serine-Threonine Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a Cyclin-Dependent Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.22 |2 NLM | |
| 650 | 7 | |a Protein Phosphatase 1 |2 NLM | |
| 650 | 7 | |a EC 3.1.3.16 |2 NLM | |
| 700 | 1 | |a Fisher, Laura A |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Williams, Byron C |e verfasserin |4 aut | |
| 700 | 1 | |a Goldberg, Michael L |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Aimin |e verfasserin |4 aut | |
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