Disassembly of Transcriptional Regulatory Complexes by Molecular Chaperones

• Published in: Science (American Association for the Advancement of Science) Vol. 296; no. 5576; pp. 2232 - 2235
• Main Authors: Freeman, Brian C., Yamamoto, Keith R.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 21.06.2002; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Animals; Autosomes; Biofilms; Biological and medical sciences; Cellular biology; Chromosomes; Dexamethasone - metabolism; Dexamethasone - pharmacology; DNA - metabolism; Drug regulation; Fundamental and applied biological sciences. Psychology; Gene expression; Genomics; Germ cells; HeLa Cells; Hormone receptors; Hormones; HSP70 Heat-Shock Proteins - metabolism; HSP90 Heat-Shock Proteins - metabolism; Humans; Molecular and cellular biology; Molecular chaperones; Molecular Chaperones - metabolism; Molecular genetics; Molecules; Nuclear Receptor Coactivator 2; Phosphoproteins - metabolism; Promoter Regions, Genetic; Rats; Receptors; Receptors, Cytoplasmic and Nuclear - metabolism; Receptors, Glucocorticoid - metabolism; Receptors, Retinoic Acid - metabolism; Receptors, Thyroid Hormone - metabolism; Recombinant Fusion Proteins - metabolism; Response Elements; Retinoid X Receptors; Transcription Factors - metabolism; Transcription, Genetic; Transcriptional Activation; Tryptophan Oxygenase - genetics; Tumor Cells, Cultured; Tyrosine Transaminase - genetics; Signal transduction; Eucaryote; Chaperone; Gene expression; Transcription factor; Complexes; Desassembly
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1073051

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.