relation: http://d-scholarship-dev.library.pitt.edu/20393/
title: Small molecule modulators of endogenous and co-chaperone-stimulated Hsp70 ATPase activity
creator: Fewell, SW
creator: Smith, CM
creator: Lyon, MA
creator: Dumitrescu, TP
creator: Wipf, P
creator: Day, BW
creator: Brodsky, JL
description: The molecular chaperone and cytoprotective activities of the Hsp70 and Hsp40 chaperones represent therapeutic targets for human diseases such as cancer and those that arise from defects in protein folding; however, very few Hsp70 and no Hsp40 modulators have been described. Using an assay for ATP hydrolysis, we identified and screened small molecules with structural similarity to 15-deoxyspergualin and NSC 630668-R/1 for their effects on endogenous and Hsp40-stimulated Hsp70 ATPase activity. Several of these compounds modulated Hsp70 ATPase activity, consistent with the action of NSC 630668-R/1 observed previously (Fewell, S. W., Day, B. W., and Brodsky, J. L. (2001) J. Biol. Chem. 276, 910-914). In contrast, three compounds inhibited the ability of Hsp40 to stimulate Hsp70 ATPase activity but did not affect the endogenous activity of Hsp70. Two of these agents also compromised the Hsp70/Hsp40-mediated post-translational translocation of a secreted pre-protein in vitro. Together, these data indicate the potential for continued screening of small molecule Hsp70 effectors and that specific modulators of Hsp70-Hsp40 interaction can be obtained, potentially for future therapeutic use.
date: 2004-12-03
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/20393/1/licence.txt
identifier:   Fewell, SW and Smith, CM and Lyon, MA and Dumitrescu, TP and Wipf, P and Day, BW and Brodsky, JL  (2004) Small molecule modulators of endogenous and co-chaperone-stimulated Hsp70 ATPase activity.  Journal of Biological Chemistry, 279 (49).  51131 - 51140.  ISSN 0021-9258     
relation: 10.1074/jbc.M404857200