DOI: 10.1126/science.1073051. Disassembly of Transcriptional Regulatory Complexes by Molecular Chaperones

Disassembly of Transcriptional Regulatory Complexes by Molecular Chaperones

10.1126/science.1073051

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

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.

Bibliography

Freeman, B. C., & Yamamoto, K. R. (2002). Disassembly of Transcriptional Regulatory Complexes by Molecular Chaperones. Science, 296(5576), 2232â2235.

Authors 2

Brian C. Freeman (first)
Keith R. Yamamoto (additional)

References 22 Referenced 329

10.1101/gad.831000
10.1016/0092-8674(95)90199-X
10.1073/pnas.74.7.2879
10.1016/S0021-9258(17)42806-7
10.1016/0092-8674(84)90523-3
10.1101/gad.867501
10.1210/mend-2-12-1256
10.1210/endo-119-5-2038
10.1016/S0968-0004(01)01834-5
For materials and methods see supplemental material at Science Online at www.sciencemag.org/cgi/content/full/296/5576/2232/DC1.
10.1016/S0021-9258(18)61372-9
Pratt W. B., Toft D. O., Endocrinol. Rev. 18, 306 (1997). / Endocrinol. Rev. by Pratt W. B. (1997)
B. C. Freeman K. R. Yamamoto unpublished data.
Freeman B. C., Felts S. J., Toft D. O., Yamamoto K. R., Genes Dev. 14, 422 (2000). (10.1101/gad.14.4.422) / Genes Dev. by Freeman B. C. (2000)
10.1210/mend.12.2.0065
10.1038/30775
10.1016/0022-2836(73)90405-1
10.1101/sqb.1999.64.149
10.1016/S0092-8674(00)80740-0
10.1016/S0092-8674(00)00169-0
10.1126/science.287.5456.1262
We thank D. O. Toft (Mayo Clinic) for supplying antibodies to p23 and hsp90 B. West (Plexxikon) for the gal4-hsp90 expression construct J. Iniguez (University of Michigan) for the (GRE) 2 (GAL4) 2 reporter construct and the members of the Yamamoto laboratory for discussion. We also appreciate helpful comments on the manuscript by P. Alaimo V. Denic R. Derynck A. Frankel D. Julius H. Luecke K. Shokat M. Van Gilst and W. Wang. B.C.F. was supported by a fellowship from the American Heart Association. Research support was from the National Science Foundation and the National Institutes of Health.

Dates

Type	When
Created	23 years ago (July 28, 2002, 7:06 p.m.)
Deposited	1 year, 7 months ago (Jan. 9, 2024, 10:39 p.m.)
Indexed	9 minutes ago (Aug. 27, 2025, 2:16 p.m.)
Issued	23 years, 2 months ago (June 21, 2002)
Published	23 years, 2 months ago (June 21, 2002)
Published Print	23 years, 2 months ago (June 21, 2002)

Funders 0

None

BibTeX

@article{Freeman_2002, title={Disassembly of Transcriptional Regulatory Complexes by Molecular Chaperones}, volume={296}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1073051}, DOI={10.1126/science.1073051}, number={5576}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Freeman, Brian C. and Yamamoto, Keith R.}, year={2002}, month=jun, pages={2232–2235} }

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