Homeostatic control of START through negative feedback between Cln3-Cdk1 and Rim15/Greatwall kinase in budding yeast

  1. Nicolas Talarek
  2. Elisabeth Gueydon
  3. Etienne Schwob  Is a corresponding author
  1. CNRS, Université de Montpellier, France

Abstract

How cells coordinate growth and division is key for size homeostasis. Phosphorylation by G1-CDK of Whi5/Rb inhibitors of SBF/E2F transcription factors triggers irreversible S-phase entry in yeast and metazoans, but why this occurs at a given cell size is not fully understood. We show that the yeast Rim15-Igo1,2 pathway, orthologous to Gwl-Arpp19/ENSA, is up-regulated in early G1 and helps promoting START by preventing PP2ACdc55 to dephosphorylate Whi5. RIM15 overexpression lowers cell size while IGO1,2 deletion delays START in cells with low CDK activity. Deletion of WHI5, CDC55 and ectopic CLN2 expression suppress the START delay of igo1,2∆ cells. Rim15 activity increases after cells switch from fermentation to respiration, where Igo1,2 contribute to chromosome maintenance. Interestingly Cln3-Cdk1 also inhibits Rim15 activity, which enables homeostatic control of Whi5 phosphorylation and cell cycle entry. We propose that Rim15/Gwl regulation of PP2A plays a hitherto unappreciated role in cell size homeostasis during metabolic rewiring of the cell cycle.

Article and author information

Author details

  1. Nicolas Talarek

    Institut de Génétique Moléculaire de Montpellier, CNRS, Université de Montpellier, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Elisabeth Gueydon

    Institut de Génétique Moléculaire de Montpellier, CNRS, Université de Montpellier, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Etienne Schwob

    Institut de Génétique Moléculaire de Montpellier, CNRS, Université de Montpellier, Montpellier, France
    For correspondence
    schwob@igmm.cnrs.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9369-6419

Funding

Fondation ARC pour la Recherche sur le Cancer (PJA 20151203349)

  • Etienne Schwob

Agence Nationale de la Recherche (ANR-14-CE11-0007-03)

  • Etienne Schwob

European Commission FP7 MC-IEF (628961 ESCA-Y)

  • Nicolas Talarek

Fondation ARC pour la Recherche sur le Cancer (PDF20121206166)

  • Nicolas Talarek

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Andrea Musacchio, Max Planck Institute of Molecular Physiology, Germany

Publication history

  1. Received: February 21, 2017
  2. Accepted: June 10, 2017
  3. Accepted Manuscript published: June 10, 2017 (version 1)
  4. Version of Record published: June 26, 2017 (version 2)

Copyright

© 2017, Talarek 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.

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  1. Nicolas Talarek
  2. Elisabeth Gueydon
  3. Etienne Schwob
(2017)
Homeostatic control of START through negative feedback between Cln3-Cdk1 and Rim15/Greatwall kinase in budding yeast
eLife 6:e26233.
https://doi.org/10.7554/eLife.26233

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