Document Detail


The dual-specificity phosphatase hYVH1 interacts with Hsp70 and prevents heat-shock-induced cell death.
MedLine Citation:
PMID:  18973475     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
hYVH1 [human orthologue of YVH1 (yeast VH1-related phosphatase)] is an atypical dual-specificity phosphatase that is widely conserved throughout evolution. Deletion studies in yeast have suggested a role for this phosphatase in regulating cell growth. However, the role of the human orthologue is unknown. The present study used MS to identify Hsp70 (heat-shock protein 70) as a novel hYVH1-binding partner. The interaction was confirmed using endogenous co-immunoprecipitation experiments and direct binding of purified proteins. Endogenous Hsp70 and hYVH1 proteins were also found to co-localize specifically to the perinuclear region in response to heat stress. Domain deletion studies revealed that the ATPase effector domain of Hsp70 and the zinc-binding domain of hYVH1 are required for the interaction, indicating that this association is not simply a chaperone-substrate complex. Thermal phosphatase assays revealed hYVH1 activity to be unaffected by heat and only marginally affected by non-reducing conditions, in contrast with the archetypical dual-specificity phosphatase VHR (VH1-related protein). In addition, Hsp70 is capable of increasing the phosphatase activity of hYVH1 towards an exogenous substrate under non-reducing conditions. Furthermore, the expression of hYVH1 repressed cell death induced by heat shock, H2O2 and Fas receptor activation but not cisplatin. Co-expression of hYVH1 with Hsp70 further enhanced cell survival. Meanwhile, expression of a catalytically inactive hYVH1 or a hYVH1 variant that is unable to interact with Hsp70 failed to protect cells from the various stress conditions. The results suggest that hYVH1 is a novel cell survival phosphatase that co-operates with Hsp70 to positively affect cell viability in response to cellular insults.
Authors:
Priya R Sharda; Christopher A Bonham; Eliseos J Mucaki; Zareen Butt; Panayiotis O Vacratsis
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  418     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-02-06     Completed Date:  2009-03-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  391-401     Citation Subset:  IM    
Affiliation:
Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON N9B3P4, Canada.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Cell Death / genetics,  physiology
Cell Survival / genetics
Cells, Cultured
Dual Specificity Phosphatase 1 / chemistry,  genetics,  metabolism*,  physiology*
Dual-Specificity Phosphatases / chemistry,  genetics,  metabolism,  physiology
HSP70 Heat-Shock Proteins / metabolism*
Heat-Shock Response* / physiology
Hela Cells
Humans
Molecular Chaperones / metabolism,  physiology
Protein Binding / physiology
Protein Interaction Domains and Motifs
Transfection
Chemical
Reg. No./Substance:
0/HSP70 Heat-Shock Proteins; 0/Molecular Chaperones; EC 3.1.3.48/DUSP1 protein, human; EC 3.1.3.48/Dual Specificity Phosphatase 1; EC 3.1.3.48/Dual-Specificity Phosphatases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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