Rapid Glucocorticoid Receptor Exchange at a Promoter is Coupled to Transcription and Regulated by Chaperones and Proteasomes

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2004 Mar 17

PMID 15024059

Citations 130

Authors

Diana A Stavreva

Waltraud G Muller

Gordon L Hager

Carolyn L Smith

James G McNally

Affiliations

Soon will be listed here.

Abstract

Exchange of the glucocorticoid receptor (GR) at promoter target sites provides the only known system in which transcription factor cycling at a promoter is fast, occurring on a time scale of seconds. The mechanism and function of this rapid exchange are unknown. We provide evidence that proteasome activity is required for rapid GR exchange at a promoter. We also show that chaperones, specifically hsp90, stabilize the binding of GR to the promoter, complicating models in which the associated chaperone, p23, has been proposed to induce GR removal. Our results are the first to connect chaperone and proteasome functions in setting the residence time of a transcription factor at a target promoter. Moreover, our results reveal that longer GR residence times are consistently associated with greater transcriptional output, suggesting a new paradigm in which the rate of rapid exchange provides a means to tune transcriptional levels.

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References

Stenoien D, Patel K, Mancini M, Dutertre M, Smith C, OMalley B . FRAP reveals that mobility of oestrogen receptor-alpha is ligand- and proteasome-dependent. Nat Cell Biol. 2001; 3(1):15-23. DOI: 10.1038/35050515. View

Yan F, Gao X, Lonard D, Nawaz Z . Specific ubiquitin-conjugating enzymes promote degradation of specific nuclear receptor coactivators. Mol Endocrinol. 2003; 17(7):1315-31. DOI: 10.1210/me.2002-0209. View

Muller W, Walker D, Hager G, McNally J . Large-scale chromatin decondensation and recondensation regulated by transcription from a natural promoter. J Cell Biol. 2001; 154(1):33-48. PMC: 2196867. DOI: 10.1083/jcb.200011069. View

Molinari E, Gilman M, Natesan S . Proteasome-mediated degradation of transcriptional activators correlates with activation domain potency in vivo. EMBO J. 1999; 18(22):6439-47. PMC: 1171706. DOI: 10.1093/emboj/18.22.6439. View

Walker D, Htun H, Hager G . Using inducible vectors to study intracellular trafficking of GFP-tagged steroid/nuclear receptors in living cells. Methods. 1999; 19(3):386-93. DOI: 10.1006/meth.1999.0874. View

Wickner S, Maurizi M, Gottesman S . Posttranslational quality control: folding, refolding, and degrading proteins. Science. 1999; 286(5446):1888-93. DOI: 10.1126/science.286.5446.1888. View

Luders J, Demand J, Hohfeld J . The ubiquitin-related BAG-1 provides a link between the molecular chaperones Hsc70/Hsp70 and the proteasome. J Biol Chem. 2000; 275(7):4613-7. DOI: 10.1074/jbc.275.7.4613. View

McNally J, Muller W, Walker D, Wolford R, Hager G . The glucocorticoid receptor: rapid exchange with regulatory sites in living cells. Science. 2000; 287(5456):1262-5. DOI: 10.1126/science.287.5456.1262. View

Phair R, Misteli T . High mobility of proteins in the mammalian cell nucleus. Nature. 2000; 404(6778):604-9. DOI: 10.1038/35007077. View

10.

Kruhlak M, Lever M, Fischle W, Verdin E, Bazett-Jones D, Hendzel M . Reduced mobility of the alternate splicing factor (ASF) through the nucleoplasm and steady state speckle compartments. J Cell Biol. 2000; 150(1):41-51. PMC: 2185567. DOI: 10.1083/jcb.150.1.41. View

11.

Shang Y, Hu X, DiRenzo J, Lazar M, Brown M . Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription. Cell. 2001; 103(6):843-52. DOI: 10.1016/s0092-8674(00)00188-4. View

12.

Lever M, Thng J, Sun X, Hendzel M . Rapid exchange of histone H1.1 on chromatin in living human cells. Nature. 2000; 408(6814):873-6. DOI: 10.1038/35048603. View

13.

Misteli T, Gunjan A, Hock R, Bustin M, Brown D . Dynamic binding of histone H1 to chromatin in living cells. Nature. 2000; 408(6814):877-81. DOI: 10.1038/35048610. View

14.

Connell P, Ballinger C, Jiang J, Wu Y, Thompson L, Hohfeld J . The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nat Cell Biol. 2001; 3(1):93-6. DOI: 10.1038/35050618. View

15.

Salghetti S, Caudy A, Chenoweth J, Tansey W . Regulation of transcriptional activation domain function by ubiquitin. Science. 2001; 293(5535):1651-3. DOI: 10.1126/science.1062079. View

16.

Stangl K, Gunther C, Frank T, Lorenz M, Meiners S, Ropke T . Inhibition of the ubiquitin-proteasome pathway induces differential heat-shock protein response in cardiomyocytes and renders early cardiac protection. Biochem Biophys Res Commun. 2002; 291(3):542-9. DOI: 10.1006/bbrc.2002.6476. View

17.

Gonzalez F, Delahodde A, Kodadek T, Johnston S . Recruitment of a 19S proteasome subcomplex to an activated promoter. Science. 2002; 296(5567):548-50. DOI: 10.1126/science.1069490. View

18.

Burakov D, Crofts L, Chang C, Freedman L . Reciprocal recruitment of DRIP/mediator and p160 coactivator complexes in vivo by estrogen receptor. J Biol Chem. 2002; 277(17):14359-62. DOI: 10.1074/jbc.C200099200. View

19.

Fletcher T, Xiao N, Mautino G, Baumann C, Wolford R, Warren B . ATP-dependent mobilization of the glucocorticoid receptor during chromatin remodeling. Mol Cell Biol. 2002; 22(10):3255-63. PMC: 133787. DOI: 10.1128/MCB.22.10.3255-3263.2002. View

20.

Deroo B, Rentsch C, Sampath S, Young J, DeFranco D, Archer T . Proteasomal inhibition enhances glucocorticoid receptor transactivation and alters its subnuclear trafficking. Mol Cell Biol. 2002; 22(12):4113-23. PMC: 133869. DOI: 10.1128/MCB.22.12.4113-4123.2002. View