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.
Skip Nav Destination
Follow us on Twitter @Biochem_Journal
Article navigation
March 2009
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
February 11 2009
The dual-specificity phosphatase hYVH1 interacts with Hsp70 and prevents heat-shock-induced cell death
Priya R. Sharda;
Priya R. Sharda
1Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON, Canada N9B 3P4
Search for other works by this author on:
Christopher A. Bonham;
Christopher A. Bonham
1Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON, Canada N9B 3P4
Search for other works by this author on:
Eliseos J. Mucaki;
Eliseos J. Mucaki
1Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON, Canada N9B 3P4
Search for other works by this author on:
Zareen Butt;
Zareen Butt
1Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON, Canada N9B 3P4
Search for other works by this author on:
Panayiotis O. Vacratsis
Panayiotis O. Vacratsis
1
1Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON, Canada N9B 3P4
1To whom correspondence should be addressed (email [email protected]).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
July 23 2008
Revision Received:
October 27 2008
Accepted:
October 30 2008
Accepted Manuscript online:
October 30 2008
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem J (2009) 418 (2): 391–401.
Article history
Received:
July 23 2008
Revision Received:
October 27 2008
Accepted:
October 30 2008
Accepted Manuscript online:
October 30 2008
Citation
Priya R. Sharda, Christopher A. Bonham, Eliseos J. Mucaki, Zareen Butt, Panayiotis O. Vacratsis; The dual-specificity phosphatase hYVH1 interacts with Hsp70 and prevents heat-shock-induced cell death. Biochem J 1 March 2009; 418 (2): 391–401. doi: https://doi.org/10.1042/BJ20081484
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Follow us on Twitter @Biochem_Journal
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() View past webinars > |