Fcp1 phosphatase controls Greatwall kinase to promote PP2A-B55 activation and mitotic progression

  1. Rosa Della Monica
  2. Roberta Visconti
  3. Nando Cervone
  4. Angela Flavia Serpico
  5. Domenico Grieco  Is a corresponding author
  1. CEINGE Biotecnologie Avanzate, Italy
  2. Consiglio Nazionale delle Ricerche, Italy

Abstract

During cell division, progression through mitosis is driven by a protein phosphorylation wave. This wave namely depends on an activation-inactivation cycle of cyclin B-dependent kinase (Cdk) 1 while activities of major protein phosphatases, like PP1 and PP2A, appear directly or indirectly repressed by Cdk1. However, how Cdk1 inactivation is coordinated with reactivation of major phosphatases at mitosis exit still lacks substantial knowledge. We show here that activation of PP2A-B55, a major mitosis exit phosphatase, required the phosphatase Fcp1 downstream Cdk1 inactivation in human cells. During mitosis exit, Fcp1 bound Greatwall (Gwl), a Cdk1-stimulated kinase that phosphorylates Ensa/ARPP19 and converts these proteins into potent PP2A-B55 inhibitors during mitosis onset, and dephosphorylated it at Cdk1 phosphorylation sites. Fcp1-catalyzed dephosphorylation drastically reduced Gwl kinase activity towards Ensa/ARPP19 promoting PP2A-B55 activation. Thus, Fcp1 coordinates Cdk1 and Gwl inactivation to derepress PP2A-B55, generating a dephosphorylation switch that drives mitosis progression.

Article and author information

Author details

  1. Rosa Della Monica

    CEINGE Biotecnologie Avanzate, Naples, Italy
    Competing interests
    The authors declare that no competing interests exist.
  2. Roberta Visconti

    Istituto per l'endocrinologia e l'oncologia Gaetano Salvatore"", Consiglio Nazionale delle Ricerche, Naples, Italy
    Competing interests
    The authors declare that no competing interests exist.
  3. Nando Cervone

    CEINGE Biotecnologie Avanzate, Naples, Italy
    Competing interests
    The authors declare that no competing interests exist.
  4. Angela Flavia Serpico

    CEINGE Biotecnologie Avanzate, Naples, Italy
    Competing interests
    The authors declare that no competing interests exist.
  5. Domenico Grieco

    CEINGE Biotecnologie Avanzate, Naples, Italy
    For correspondence
    domenico.grieco@unina.it
    Competing interests
    The authors declare that no competing interests exist.

Copyright

© 2015, Della Monica et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,314
    views
  • 404
    downloads
  • 28
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Rosa Della Monica
  2. Roberta Visconti
  3. Nando Cervone
  4. Angela Flavia Serpico
  5. Domenico Grieco
(2015)
Fcp1 phosphatase controls Greatwall kinase to promote PP2A-B55 activation and mitotic progression
eLife 4:e10399.
https://doi.org/10.7554/eLife.10399

Share this article

https://doi.org/10.7554/eLife.10399

Further reading

    1. Cell Biology
    Yan Song, Linda J Fothergill ... Gene W Yeo
    Research Article

    Dynamic interactions between gut mucosal cells and the external environment are essential to maintain gut homeostasis. Enterochromaffin (EC) cells transduce both chemical and mechanical signals and produce 5-hydroxytryptamine to mediate disparate physiological responses. However, the molecular and cellular basis for functional diversity of ECs remains to be adequately defined. Here, we integrated single-cell transcriptomics with spatial image analysis to identify 14 EC clusters that are topographically organized along the gut. Subtypes predicted to be sensitive to the chemical environment and mechanical forces were identified that express distinct transcription factors and hormones. A Piezo2+ population in the distal colon was endowed with a distinctive neuronal signature. Using a combination of genetic, chemogenetic, and pharmacological approaches, we demonstrated Piezo2+ ECs are required for normal colon motility. Our study constructs a molecular map for ECs and offers a framework for deconvoluting EC cells with pleiotropic functions.

    1. Cell Biology
    2. Developmental Biology
    Sarah Y Coomson, Salil A Lachke
    Insight

    A study in mice reveals key interactions between proteins involved in fibroblast growth factor signaling and how they contribute to distinct stages of eye lens development.