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PMID: 9321400 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

GrpE-like regulation of the hsc70 chaperone by the anti-apoptotic protein BAG-1.

The EMBO journal ·Vol. 16 ·No. 20 ·1997-10-15 ·Pages 6209-16

Höhfeld J, Jentsch S

Abstract

The BAG-1 protein appears to inhibit cell death by binding to Bcl-2, the Raf-1 protein kinase, and certain growth factor receptors, but the mechanism of inhibition remains enigmatic. BAG-1 also interacts with several steroid hormone receptors which require the molecular chaperones Hsc70 and Hsp90 for activation. Here we show that BAG-1 is a regulator of the Hsc70 chaperone. BAG-1 binds to the ATPase domain of Hsc70 and, in cooperation with Hsp40, stimulates Hsc70's steady-state ATP hydrolysis activity approximately 40-fold. Similar to the action of the GrpE protein on bacterial Hsp70, BAG-1 accelerates the release of ADP from Hsc70. Thus, BAG-1 regulates the Hsc70 ATPase in a manner contrary to the Hsc70-interacting protein Hip, which stabilizes the ADP-bound state. Intriguingly, BAG-1 and Hip compete in binding to the ATPase domain of Hsc70. Our results reveal an unexpected diversity in the regulation of Hsc70 and raise the possibility that the observed anti-apoptotic function of BAG-1 may be exerted through a modulation of the chaperone activity of Hsc70 on specific protein folding and maturation pathways.

MeSH Terms
Adenosine Diphosphate/metabolism Adenosine Triphosphatases/metabolism Adenosine Triphosphate/metabolism Apoptosis/physiology Carrier Proteins/isolation & purification,metabolism DNA-Binding Proteins HSC70 Heat-Shock Proteins HSP40 Heat-Shock Proteins HSP70 Heat-Shock Proteins/metabolism Heat-Shock Proteins/metabolism Humans Models, Biological Molecular Chaperones/metabolism Protein Binding Transcription Factors
Chemicals
BCL2-associated athanogene 1 protein Carrier Proteins DNA-Binding Proteins DNAJB1 protein, human GRPEL1 protein, human GrpE-like 1 mitochondrial protein, vertebrate HSC70 Heat-Shock Proteins HSP40 Heat-Shock Proteins HSP70 Heat-Shock Proteins HSPA8 protein, human Heat-Shock Proteins Hip chaperone Molecular Chaperones Transcription Factors Adenosine Diphosphate Adenosine Triphosphate Adenosine Triphosphatases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Höhfeld J
ZMBH, Zentrum für Molekulare Biologie, Universität Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany. j-hoehfeld@sun0.urz.uni-heidelberg.de
Jentsch S
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/16.20.6209
Email
j-hoehfeld@sun0.urz.uni-heidelberg.de
Published
1997-10-15
Pages
6209-16
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1326305
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1093/emboj/16.20.6209 PMC Full Text View journal details
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