Disassembly of transcriptional regulatory complexes by molecular chaperones.
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.
Freeman
Brian C
BC
Department of Cell and Structural Biology, University of Illinois, Urbana-Champaign, 601 South Goodwin Avenue, Urbana, IL 61801, USA.
Yamamoto
Keith R
KR
D000818:Animals; D004247:DNA / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism*; D051958:Nuclear Receptor Coactivator 2; D010750:Phosphoproteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D000071876:Prostaglandin-E Synthases; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020218:Response Elements; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014366:Tryptophan Oxygenase / Q000235:genetics; D014407:Tumor Cells, Cultured; D014444:Tyrosine Transaminase / Q000235:genetics
D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D051958:Nuclear Receptor Coactivator 2; D010750:Phosphoproteins; D018160:Receptors, Cytoplasmic and Nuclear; D011965:Receptors, Glucocorticoid; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D047488:Retinoid X Receptors; D014157:Transcription Factors; D003907:Dexamethasone; D004247:DNA; D014366:Tryptophan Oxygenase; D014444:Tyrosine Transaminase; C490849:PTGES3 protein, human; D000071876:Prostaglandin-E Synthases