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The Greatwall–PP2A Axis in Cell Cycle Control

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Cell Cycle Control

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1170))

Abstract

Cell cycle progression is largely controlled by reversible protein phosphorylation mediated by cyclically activated kinases and phosphatases. It has long been known that cyclin B–Cdk1 activation triggers mitotic entry, and the enzymatic network controlling its activation and inactivation has been well characterized. Much more recently protein phosphatase 2A (PP2A) together with its B55 regulatory subunit has been recognized as the major activity dephosphorylating Cdk1 targets. Moreover, PP2A-B55 activity is high in late M phase and interphase, but low at mitotic entry. A series of discoveries in the fly and frog model systems have uncovered the molecular mechanism mediating this regulation. The Greatwall (Gwl) kinase activates endosulfines, which become specific inhibitors of PP2A-B55. Cdk1-dependent activation of Gwl at mitotic entry leads to PP2A-B55 downregulation, which synergizes with Cdk1 activation to promote the phosphorylated states of several mitotic substrates. Much less is known on the mechanisms inactivating Gwl and endosulfines at mitotic exit. Recent reports show the importance of spatiotemporal regulation of Gwl, endosulfines, and PP2A-B55 for cell cycle progression. The various systems and cell types differ in their dependence on the Gwl–PP2A axis for cell cycle progression. Moreover, this pathway also regulates gene expression in yeast, and this function could be conserved in metazoans.

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Acknowledgements

Work on the Gwl–PP2A axis in V.A.’s lab is supported by the Canadian Institutes of Health Research (CIHR). V.A. also holds a New Investigator Award from the CIHR. P.W. holds a studentship from the Fonds de recherche du Québec—Santé (FRQ-S). IRIC is supported in part by the Canadian Center of Excellence in Commercialization and Research, the Canada Foundation for Innovation, and the FRQ-S. Work in M.M.’s laboratory was funded by grants from Bayer Pharma AG, Fundación Ramón Areces, MINECO (SAF2012-38215), the OncoCycle Programme (S2010/BMD-2470) from the Comunidad de Madrid, and the European Union Seventh Framework Programme (MitoSys project; HEALTH-F5-2010-241548).

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Authors and Affiliations

  1. Department of Biochemistry, Institut de recherche en immunologie et en cancérologie, Université de Montréal, Édouard-Montpetit Blvd., Montréal, QC, Canada, H3T 1J4

    Peng Wang & Vincent Archambault

  2. Spanish National Cancer Research Centre (CNIO), Madrid, Spain

    Marcos Malumbres

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  1. Peng Wang
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  2. Marcos Malumbres
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  3. Vincent Archambault
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Correspondence to Vincent Archambault .

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Editors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA

    Eishi Noguchi

  2. Dept of Biochemistry & Molecular Biology, Drexel University College of Medicine, Philadelphia, USA

    Mariana C. Gadaleta

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Wang, P., Malumbres, M., Archambault, V. (2014). The Greatwall–PP2A Axis in Cell Cycle Control. In: Noguchi, E., Gadaleta, M. (eds) Cell Cycle Control. Methods in Molecular Biology, vol 1170. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0888-2_6

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  • DOI: https://doi.org/10.1007/978-1-4939-0888-2_6

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-0887-5

  • Online ISBN: 978-1-4939-0888-2

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