Document Detail

Hog1 mediates cell-cycle arrest in G1 phase by the dual targeting of Sic1.
MedLine Citation:
PMID:  15448699     Owner:  NLM     Status:  MEDLINE    
Activation of stress-activated protein kinases (SAPKs) is essential for proper cell adaptation to extracellular stimuli. The exposure of yeast cells to high osmolarity, or mutations that lead to activation of the Hog1 SAPK, result in cell-cycle arrest. The mechanisms by which Hog1 and SAPKs in general regulate cell-cycle progression are not completely understood. Here we show that Hog1 regulates cell cycle progression at the G1 phase by a dual mechanism that involves downregulation of cyclin expression and direct targeting of the CDK-inhibitor protein Sic1. Hog1 interacts physically with Sic1 in vivo and in vitro, and phosphorylates a single residue at the carboxyl terminus of Sic1, which, in combination with the downregulation of cyclin expression, results in Sic1 stabilization and inhibition of cell-cycle progression. Cells lacking Sic1 or containing a Sic1 allele mutated in the Hog1 phosphorylation site are unable to arrest at G1 phase after Hog1 activation, and become sensitive to osmostress. Together, our data indicate that the Sic1 CDK-inhibitor is the molecular target for the SAPK Hog1 that is required to modulate cell-cycle progression in response to stress.
Xavier Escoté; Meritxell Zapater; Josep Clotet; Francesc Posas
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-09-19
Journal Detail:
Title:  Nature cell biology     Volume:  6     ISSN:  1465-7392     ISO Abbreviation:  Nat. Cell Biol.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-10-01     Completed Date:  2004-11-09     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  100890575     Medline TA:  Nat Cell Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  997-1002     Citation Subset:  IM    
Cell Signaling Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, E-08003 Barcelona, Spain.
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MeSH Terms
Antibodies, Monoclonal / metabolism
Cyclin-Dependent Kinase Inhibitor Proteins
Cyclins / metabolism
Enzyme Activation
G1 Phase*
Gene Expression Regulation, Fungal*
Mitogen-Activated Protein Kinases / metabolism*
Osmotic Pressure
Saccharomyces cerevisiae / chemistry
Saccharomyces cerevisiae Proteins / chemistry,  genetics*,  metabolism*
Two-Hybrid System Techniques
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Cyclin-Dependent Kinase Inhibitor Proteins; 0/Cyclins; 0/SIC1 protein, S cerevisiae; 0/Saccharomyces cerevisiae Proteins; EC 2.7.10.-/HOG1 protein, S cerevisiae; EC Protein Kinases

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