Redox-regulated cochaperone activity of the human DnaJ homolog Hdj2

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Title
Redox-regulated cochaperone activity of the human DnaJ homolog Hdj2
Author(s)
Hoon-In Choi; Sang Pil Lee; Kyung Soon Kim; Chae Young Hwang; Yu Ran Lee; S K Chae; Y S Kim; H Z Chae; Ki Sun Kwon
Bibliographic Citation
Free Radical Biology and Medicine, vol. 40, no. 4, pp. 651-659
Publication Year
2006
Abstract
The human DnaJ homolog Hdj2 is a cochaperone containing a cysteine-rich zinc finger domain. We identified a specific interaction of Hdj2 with the cellular redox enzyme thioredoxin using a yeast two-hybrid assay and a coimmunoprecipitation assay, thereby investigating how the redox environment of the cell regulates Hdj2 function. In reconstitution experiments with Hsc70, we found that treatment with H2O2 caused the oxidative inactivation of Hdj2 cochaperone activity. Hdj2 inactivation paralleled the oxidation of cysteine thiols and concomitant release of coordinated zinc, suggesting a role of cysteine residues in the zinc finger domain of Hdj2 as a redox sensor of chaperone-mediated protein-folding machinery. H 2O2-induced negative regulation of Hdj2 cochaperone activity was also confirmed in mammalian cells using luciferase as a foreign reporter cotransfected with Hsc70 and Hdj2. The in vivo oxidation of cysteine residues in Hdj2 was detected only in thioredoxin-knockdown cells, implying that thioredoxin is involved in the in vivo reduction. The oxidative inactivation of Hdj2 was reversible. Wild-type thioredoxin notably recovered the oxidatively inactivated Hdj2 activity accompanied by the reincorporation of zinc, whereas the catalytically inactive mutant thioredoxin (Cys32Ser/Cys35Ser) did not. Taken together, we propose that oxidation and reduction reversibly regulate Hdj2 function in response to the redox states of the cell.
Keyword
chaperonefree radicaloxidative stressprotein foldingthioredoxinzinc finger
ISSN
0891-5849
Publisher
Elsevier
DOI
http://dx.doi.org/10.1177/0095399705282879
Type
Article
Appears in Collections:
Aging Convergence Research Center > 1. Journal Articles
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