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- Title
GrpE-like regulation of the Hsc70 chaperone by the anti-apoptotic protein BAG-1.
- Authors
Höhfeld, Jörg; Jentsch, Stefan
- 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 ∼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.
- Subjects
APOPTOSIS; CELL death; PROTEINS; PROTEIN kinases; ADENOSINE triphosphatase; STEROID hormones; GROWTH factors; MOLECULAR chaperones
- Publication
EMBO Journal, 1997, Vol 16, Issue 20, p6209
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1093/emboj/16.20.6209