The Ubiquitin-related BAG-1 Provides a Link between the Molecular Chaperones Hsc70/Hsp70 and the Proteasome*
- From the Department of Molecular Cell Biology, Max Planck Institute for Biochemistry, Am Klopferspitz 18a, D-82152 Martinsried, Germany
Abstract
The BAG-1 protein modulates the chaperone activity of Hsc70 and Hsp70 in the mammalian cytosol and nucleus. Remarkably, BAG-1 possesses a ubiquitin-like domain at its amino terminus, suggesting a link to the ubiquitin/proteasome system. Here we show that BAG-1 is indeed associated with the 26 S proteasome in HeLa cells. Binding of the chaperone cofactor to the proteolytic complex is regulated by ATP hydrolysis and is not mediated by Hsc70 and Hsp70. The presented findings reveal a role of BAG-1 as a physical link between the Hsc70/Hsp70 chaperone system and the proteasome. In fact, targeting of BAG-1 to the proteasome promotes an association of the chaperones with the proteolytic complex in vitro and in vivo. A regulatory function of the chaperone cofactor at the interface between protein folding and protein degradation is thus indicated.
Footnotes
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↵* This work was supported by Deutsche Forschungsgemeinschaft Grants HO 1518/2-1, 2-2, and 3-1.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ To whom correspondence should be addressed. Tel.: 49-89-8578-3027; Fax: 49-89-8578-3022; E-mail: hoehfeld@biochem.mpg.de.
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↵2 J. Höhfeld, unpublished observations.
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↵3 J. Demand, and J. Höhfeld, unpublished observations.
- Abbreviations:
- Hsp70
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70-kDa heat shock protein family
- MEM
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minimal essential medium
- PAGE
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polyacrylamide gel electrophoresis
- PBS
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phosphate-buffered saline
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- Received August 27, 1999.
- Revision received November 18, 1999.
- The American Society for Biochemistry and Molecular Biology, Inc.
