Title

Functional characterization of the interaction between heat shock protein 70 and the human dual-specificity phosphatase YVH1

Date of Award

2008

Degree Type

Thesis

Degree Name

M.Sc.

Department

Chemistry and Biochemistry

First Advisor

Vacratsis, Panayiotis (Chemistry & Biochemistry)

Keywords

Biochemistry, General.

Rights

CC BY-NC-ND 4.0

Abstract

YVH1 (DUSP12) is a highly conserved atypical dual-specificity phosphatase. Yeast deletion studies have suggested YVH1 plays a role in cell growth. However, the physiological role of the human orthologue is unknown. Our lab has determined that hYVH1 interacts with HSP70, a heat shock protein that plays a cell survival role. The focus of this study was to further characterize this interaction, and attempt to determine its functional significance. Results determined that this interaction is mediated through the ATPase domain of HSP70 and requires the zinc binding domain of hYVH1. Moreover, hYVH1 was found to be uncompetitively inhibited by ATP. Functional examination determined that catalytic activity of each enzyme is not affected by this interaction. Evidence suggests that over-expression of hYVH1 alters the localization of HSP70 during heat stress. Therefore, our results suggest that the HSP70-hYVH1 interaction may be critical for positioning these cell survival proteins during times of cellular stress.