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CDK-Dependent Hsp70 Phosphorylation Controls G1 Cyclin Abundance and Cell-Cycle Progression.
MedLine Citation:
PMID:  23217712     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
In budding yeast, the essential functions of Hsp70 chaperones Ssa1-4 are regulated through expression level, isoform specificity, and cochaperone activity. Suggesting a novel regulatory paradigm, we find that phosphorylation of Ssa1 T36 within a cyclin-dependent kinase (CDK) consensus site conserved among Hsp70 proteins alters cochaperone and client interactions. T36 phosphorylation triggers displacement of Ydj1, allowing Ssa1 to bind the G1 cyclin Cln3 and promote its degradation. The stress CDK Pho85 phosphorylates T36 upon nitrogen starvation or pheromone stimulation, destabilizing Cln3 to delay onset of S phase. In turn, the mitotic CDK Cdk1 phosphorylates T36 to block Cln3 accumulation in G2/M. Suggesting broad conservation from yeast to human, CDK-dependent phosphorylation of Hsc70 T38 similarly regulates Cyclin D1 binding and stability. These results establish an active role for Hsp70 chaperones as signal transducers mediating growth control of G1 cyclin abundance and activity.
Authors:
Andrew W Truman; Kolbrun Kristjansdottir; Donald Wolfgeher; Naushaba Hasin; Sigrun Polier; Hong Zhang; Sarah Perrett; Chrisostomos Prodromou; Gary W Jones; Stephen J Kron
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cell     Volume:  151     ISSN:  1097-4172     ISO Abbreviation:  Cell     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1308-18     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL 60637, USA; Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA.
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