Logo image
Back
PP2A(Cdc55) regulates G(1) cyclin stability
Journal article   Open access   Peer reviewed

PP2A(Cdc55) regulates G(1) cyclin stability

Paula McCourt, Christina Gallo-Ebert, Yan Gonghong, Yu Jiang and Joseph T. Nickels
Cell cycle (Georgetown, Tex.), v 12(8), pp 1201-1210
15 Apr 2013
DOI: https://doi.org/10.4161/cc.24231
PMID: 23518505
url
https://doi.org/10.4161/cc.24231View
Published, Version of Record (VoR) Open

Abstract

Cell Biology Life Sciences & Biomedicine Science & Technology
Maintaining accurate progression through the cell cycle requires the proper temporal expression and regulation of cyclins. The mammalian D-type cyclins promote G(1)-S transition. D1 cyclin protein stability is regulated through its ubiquitylation and resulting proteolysis catalyzed by the SCF E3 ubiquitin ligase complex containing the F-box protein, Fbx4. SCF E3-ligase-dependent ubiquitylation of D1 is trigged by an increase in the phosphorylation status of the cyclin. As inhibition of ubiquitin-dependent D1 degradation is seen in many human cancers, we set out to uncover how D-type cyclin phosphorylation is regulated. Here we show that in S. cerevisiae, a heterotrimeric protein phosphatase 2A (PP2A(Cdc55)) containing the mammalian PPP2R2/PR55 B subunit ortholog Cdc55 regulates the stability of the G(1) cyclin Cln2 by directly regulating its phosphorylation state. Cells lacking Cdc55 contain drastically reduced Cln2 levels caused by degradation due to cdk-dependent hyperphosphorylation, as a Cln2 mutant unable to be phosphorylated by the yeast cdk Cdc28 is highly stable in cdc55-null cells. Moreover, cdc55-null cells become inviable when the SCFGrr1 activity known to regulate Cln2 levels is eliminated or when Cln2 is overexpressed, indicating a critical relationship between SCF and PP2A functions in regulating cell cycle progression through modulation of G(1)-S cyclin degradation/stability. In sum, our results indicate that PP2A is absolutely required to maintain G(1)-S cyclin levels through modulating their phosphorylation status, an event necessary to properly transit through the cell cycle.

Metrics

2 Record Views
9 citations in Web of Science
10 citations in Scopus

Details

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Web of Science research areas
Cell Biology
Logo image