Homeostatic control of START through negative feedback between Cln3-Cdk1 and Rim15/Greatwall kinase in budding yeast
- 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
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.
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.
Metrics
-
- 2,212
- views
-
- 393
- downloads
-
- 38
- 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)
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
