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Science 296 (5576): 2232-2235

Copyright © 2002 by the American Association for the Advancement of Science

Disassembly of Transcriptional Regulatory Complexes by Molecular Chaperones

Brian C. Freeman,1 Keith R. Yamamoto2*

Many biological processes are initiated by cooperative assembly of large multicomponent complexes; however, mechanisms for modulating or terminating the actions of these complexes are not well understood. For example, hormone-bound intracellular receptors (IRs) nucleate formation of transcriptional regulatory complexes whose actions cease promptly upon hormone withdrawal. Here, we show that the p23 molecular chaperone localizes in vivo to genomic response elements in a hormone-dependent manner, disrupting receptor-mediated transcriptional activation in vivo and in vitro; Hsp90 weakly displayed similar activities. Indeed, p23 and Hsp90 also disrupted the activities of some non-IR-containing transcriptional regulatory complexes. We suggest that molecular chaperones promote disassembly of transcriptional regulatory complexes, thus enabling regulatory machineries to detect and respond to signaling changes.

1 Department of Cell and Structural Biology, University of Illinois, Urbana-Champaign, 601 South Goodwin Avenue, Urbana, IL 61801, USA.
2 Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 513 Parnassus, San Francisco, CA 94143-0450, USA.
*   To whom correspondence should be addressed. E-mail: yamamoto{at}cgl.ucsf.edu

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