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Nat Commun. 2017 Aug 8;8(1):206. doi: 10.1038/s41467-017-00339-4.

Ensa controls S-phase length by modulating Treslin levels.

Author information

1
Université de Montpellier, Centre de Recherche de Biologie Cellulaire de Montpellier, Equipe Labellisée 'Ligue Contre le Cancer', CNRS UMR 5237, 1919 Route de Mende, 34293, Montpellier cedex 5, France.
2
The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia.
3
St. Vincent's Clinical School, Faculty of Medicine, UNSW, Darlinghurst, NSW, 2010, Australia.
4
Institute of Molecular Genetics, CNRS UMR 5535, University of Montpellier, 1919 Route de Mende, 34293, Montpellier, France.
5
Université de Montpellier, Centre de Recherche de Biologie Cellulaire de Montpellier, Equipe Labellisée 'Ligue Contre le Cancer', CNRS UMR 5237, 1919 Route de Mende, 34293, Montpellier cedex 5, France. thierry.lorca@crbm.cnrs.fr.
6
Université de Montpellier, Centre de Recherche de Biologie Cellulaire de Montpellier, Equipe Labellisée 'Ligue Contre le Cancer', CNRS UMR 5237, 1919 Route de Mende, 34293, Montpellier cedex 5, France. anna.castro@crbm.cnrs.fr.

Abstract

The Greatwall/Ensa/PP2A-B55 pathway is essential for controlling mitotic substrate phosphorylation and mitotic entry. Here, we investigate the effect of the knockdown of the Gwl substrate, Ensa, in human cells. Unexpectedly, Ensa knockdown promotes a dramatic extension of S phase associated with a lowered density of replication forks. Notably, Ensa depletion results in a decrease of Treslin levels, a pivotal protein for the firing of replication origins. Accordingly, the extended S phase in Ensa-depleted cells is completely rescued by the overexpression of Treslin. Our data herein reveal a new mechanism by which normal cells regulate S-phase duration by controlling the ubiquitin-proteasome degradation of Treslin in a Gwl/Ensa-dependent pathway.The Greatwall/Ensa/PP2A-B55 pathway controls mitotic substrate phosphorylation and mitotic entry. Here the authors show that cells regulate S phase duration by controlling the ubiquitin-proteasome degradation of Treslin in a Gwl/Ensa-dependent pathway.

PMID:
28785014
PMCID:
PMC5547116
DOI:
10.1038/s41467-017-00339-4
[Indexed for MEDLINE]
Free PMC Article

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