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PP1-mediated dephosphorylation of phosphoproteins at mitotic exit is controlled by inhibitor-1 and PP1 phosphorylation
Open accessAbstract
Loss of cell division cycle 2 (Cdc2, also known as Cdk1) activity after cyclin B degradation is necessary, but not sufficient, for mitotic exit. Proteins phosphorylated by Cdc2 and downstream mitotic kinases must be dephosphorylated. We report here that protein phosphatase-1 (PP1) is the main catalyst of mitotic phosphoprotein dephosphorylation. Suppression of PP1 during early mitosis is maintained through dual inhibition by Cdc2 phosphorylation and the binding of inhibitor-1. Protein kinase A (PKA) phosphorylates inhibitor-1, mediating binding to PP1. As Cdc2 levels drop after cyclin B degradation, auto-dephosphorylation of PP1 at its Cdc2 phosphorylation site (Thr 320) allows partial PP1 activation. This promotes PP1-regulated dephosphorylation at the activating site of inhibitor-1 (Thr 35) followed by dissociation of the inhibitor-1–PP1 complex and then full PP1 activation to promote mitotic exit. Thus, Cdc2 both phosphorylates multiple mitotic substrates and inhibits their PP1-mediated dephosphorylation.
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Cited by
Greatwall Phosphorylates an Inhibitor of Protein Phosphatase 2Α That Is Essential for Mitosis
Mochida, S., Maslen, S. L., Skehel, M., & Hunt, T. (2010) · Science · doi:10.1126/science.1195689 · Cited by 425
Mochida, S., Ikeo, S., Gannon, J., & Hunt, T. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.238 · Cited by 275
Protein Serine/Threonine Phosphatases: Keys to Unlocking Regulators and Substrates
Brautigan, D. L., & Shenolikar, S. (2018) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-062917-012332 · Cited by 191
A PP1-PP2A phosphatase relay controls mitotic progression
Grallert, A., Boke, E., Hagting, A., Hodgson, B., Connolly, Y., Griffiths, J. R., Smith, D. L., Pines, J., & Hagan, I. M. (2015) · Nature · doi:10.1038/nature14019 · Cited by 188
Self-organization of intracellular gradients during mitosis
Fuller, B. G. (2010) · Cell Division · doi:10.1186/1747-1028-5-5 · Cited by 42
Metadata
- Authors
- Wu, J. Q., Guo, J. Y., Tang, W., Yang, C.-S., Freel, C. D., Chen, C., Nairn, A. C., & Kornbluth, S.
- Venue
- Nature Cell Biology
- Published
- 2009-04-26
- Volume
- 11
- Issue
- 5
- Pages
- 644-651
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2095346103
- Cited by
- 234
- References
- 0
- FWCI
- 9.35
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: PP1-mediated dephosphorylation of phosphoproteins at mitotic exit is controlled by inhibitor-1 and PP1 phosphorylation. https://app.cochat.ai/papers/10.1038/ncb1871
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- Wu, J. Q., Guo, J. Y., Tang, W., Yang, C.-S., Freel, C. D., Chen, C., Nairn, A. C., & Kornbluth, S. (2009). PP1-mediated dephosphorylation of phosphoproteins at mitotic exit is controlled by inhibitor-1 and PP1 phosphorylation. Nature Cell Biology. https://doi.org/10.1038/ncb1871
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