Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 21 June 2002:
Vol. 296. no. 5576, pp. 2232 - 2235
DOI: 10.1126/science.1073051
Prev | Table of Contents | Next

Reports

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

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Hsp90{beta} and p130cas: novel regulatory factors of MMP-13 expression in human osteoarthritic chondrocytes.
Z Fan, G Tardif, D Hum, N Duval, J-P Pelletier, and J Martel-Pelletier (2009)
Ann Rheum Dis 68, 976-982
   Abstract »    Full Text »    PDF »
The human CDK8 subcomplex is a molecular switch that controls Mediator coactivator function.
M. T. Knuesel, K. D. Meyer, C. Bernecky, and D. J. Taatjes (2009)
Genes & Dev. 23, 439-451
   Abstract »    Full Text »    PDF »
Trithorax requires Hsp90 for maintenance of active chromatin at sites of gene expression.
M. Tariq, U. Nussbaumer, Y. Chen, C. Beisel, and R. Paro (2009)
PNAS 106, 1157-1162
   Abstract »    Full Text »    PDF »
From hatching to dispatching: the multiple cellular roles of the Hsp70 molecular chaperone machinery.
E. Meimaridou, S. B Gooljar, and J P. Chapple (2009)
J. Mol. Endocrinol. 42, 1-9
   Abstract »    Full Text »    PDF »
Minireview: The Intersection of Steroid Receptors with Molecular Chaperones: Observations and Questions.
D. F. Smith and D. O. Toft (2008)
Mol. Endocrinol. 22, 2229-2240
   Abstract »    Full Text »    PDF »
Regulation of TATA-binding protein dynamics in living yeast cells.
R. O. Sprouse, T. S. Karpova, F. Mueller, A. Dasgupta, J. G. McNally, and D. T. Auble (2008)
PNAS 105, 13304-13308
   Abstract »    Full Text »    PDF »
Intra- and Intermonomer Interactions Are Required to Synergistically Facilitate ATP Hydrolysis in Hsp90.
C. N. Cunningham, K. A. Krukenberg, and D. A. Agard (2008)
J. Biol. Chem. 283, 21170-21178
   Abstract »    Full Text »    PDF »
Novel Steroid Receptor Phyto-Modulator Compound A Inhibits Growth and Survival of Prostate Cancer Cells.
A. Yemelyanov, J. Czwornog, L. Gera, S. Joshi, R. T. Chatterton Jr., and I. Budunova (2008)
Cancer Res. 68, 4763-4773
   Abstract »    Full Text »    PDF »
p23/Sba1p Protects against Hsp90 Inhibitors Independently of Its Intrinsic Chaperone Activity.
F. Forafonov, O. A. Toogun, I. Grad, E. Suslova, B. C. Freeman, and D. Picard (2008)
Mol. Cell. Biol. 28, 3446-3456
   Abstract »    Full Text »    PDF »
HSP90/70 chaperones are required for rapid nucleosome removal upon induction of the GAL genes of yeast.
M. Floer, G. O. Bryant, and M. Ptashne (2008)
PNAS 105, 2975-2980
   Abstract »    Full Text »    PDF »
The Heat Shock Protein 70 Cochaperone YDJ1 Is Required for Efficient Membrane-Specific Flock House Virus RNA Replication Complex Assembly and Function in Saccharomyces cerevisiae.
S. A. Weeks and D. J. Miller (2008)
J. Virol. 82, 2004-2012
   Abstract »    Full Text »    PDF »
Molecular chaperone Hsp90 stabilizes Pih1/Nop17 to maintain R2TP complex activity that regulates snoRNA accumulation.
R. Zhao, Y. Kakihara, A. Gribun, J. Huen, G. Yang, M. Khanna, M. Costanzo, R. L. Brost, C. Boone, T. R. Hughes, et al. (2008)
J. Cell Biol. 180, 563-578
   Abstract »    Full Text »    PDF »
Dynamics of the Hypoxia-inducible Factor-1-Vascular Endothelial Growth Factor Promoter Complex.
P. Yu and T. Kodadek (2007)
J. Biol. Chem. 282, 35035-35045
   Abstract »    Full Text »    PDF »
UXT is a novel and essential cofactor in the NF-{kappa}B transcriptional enhanceosome.
S. Sun, Y. Tang, X. Lou, L. Zhu, K. Yang, B. Zhang, H. Shi, and C. Wang (2007)
J. Cell Biol. 178, 231-244
   Abstract »    Full Text »    PDF »
cPGES/p23 Is Required for Glucocorticoid Receptor Function and Embryonic Growth but Not Prostaglandin E2 Synthesis.
A. K. Lovgren, M. Kovarova, and B. H. Koller (2007)
Mol. Cell. Biol. 27, 4416-4430
   Abstract »    Full Text »    PDF »
The p23 molecular chaperone promotes functional telomerase complexes through DNA dissociation.
O. A. Toogun, W. Zeiger, and B. C. Freeman (2007)
PNAS 104, 5765-5770
   Abstract »    Full Text »    PDF »
The Ligand Binding Domain Controls Glucocorticoid Receptor Dynamics Independent of Ligand Release.
S. H. Meijsing, C. Elbi, H. F. Luecke, G. L. Hager, and K. R. Yamamoto (2007)
Mol. Cell. Biol. 27, 2442-2451
   Abstract »    Full Text »    PDF »
Ligand-Specific Dynamics of the Androgen Receptor at Its Response Element in Living Cells.
T. I. Klokk, P. Kurys, C. Elbi, A. K. Nagaich, A. Hendarwanto, T. Slagsvold, C.-Y. Chang, G. L. Hager, and F. Saatcioglu (2007)
Mol. Cell. Biol. 27, 1823-1843
   Abstract »    Full Text »    PDF »
Thyroid Hormones Signaling Is Getting More Complex: STORMs Are Coming.
F. Flamant, K. Gauthier, and J. Samarut (2007)
Mol. Endocrinol. 21, 321-333
   Abstract »    Full Text »    PDF »
Protein Kinase A Exhibits Selective Modulation of Estradiol-Dependent Transcription in Breast Cancer Cells that Is Associated with Decreased Ligand Binding, Altered Estrogen Receptor {alpha} Promoter Interaction, and Changes in Receptor Phosphorylation.
M. H. Al-Dhaheri and B. G. Rowan (2007)
Mol. Endocrinol. 21, 439-456
   Abstract »    Full Text »    PDF »
The Activity and Stability of the Transcriptional Coactivator p/CIP/SRC-3 Are Regulated by CARM1-Dependent Methylation.
H. Naeem, D. Cheng, Q. Zhao, C. Underhill, M. Tini, M. T. Bedford, and J. Torchia (2007)
Mol. Cell. Biol. 27, 120-134
   Abstract »    Full Text »    PDF »
The role of the proteasomal ATPases and activator monoubiquitylation in regulating Gal4 binding to promoters.
A. Ferdous, D. Sikder, T. Gillette, K. Nalley, T. Kodadek, and S. A. Johnston (2007)
Genes & Dev. 21, 112-123
   Abstract »    Full Text »    PDF »
Unliganded and hormone-bound glucocorticoid receptors interact with distinct hydrophobic sites in the Hsp90 C-terminal domain.
L. Fang, D. Ricketson, L. Getubig, and B. Darimont (2006)
PNAS 103, 18487-18492
   Abstract »    Full Text »    PDF »
Overview of Nomenclature of Nuclear Receptors.
P. Germain, B. Staels, C. Dacquet, M. Spedding, and V. Laudet (2006)
Pharmacol. Rev. 58, 685-704
   Abstract »    Full Text »    PDF »
The Hsp90 Cochaperone p23 Is Essential for Perinatal Survival.
I. Grad, T. A. McKee, S. M. Ludwig, G. W. Hoyle, P. Ruiz, W. Wurst, T. Floss, C. A. Miller III, and D. Picard (2006)
Mol. Cell. Biol. 26, 8976-8983
   Abstract »    Full Text »    PDF »
Signaling within a Coactivator Complex: Methylation of SRC-3/AIB1 Is a Molecular Switch for Complex Disassembly.
Q. Feng, P. Yi, J. Wong, and B. W. O'Malley (2006)
Mol. Cell. Biol. 26, 7846-7857
   Abstract »    Full Text »    PDF »
The Cochaperone p23 Differentially Regulates Estrogen Receptor Target Genes and Promotes Tumor Cell Adhesion and Invasion..
E. Oxelmark, J. M. Roth, P. C. Brooks, S. E. Braunstein, R. J. Schneider, and M. J. Garabedian (2006)
Mol. Cell. Biol. 26, 5205-5213
   Abstract »    Full Text »    PDF »
Genes invoked in the ovarian transition to menopause.
A. Zimon, A. Erat, T. V. Wald, B. Bissell, A. Koulova, C. H. Choi, D. Bachvarov, R. H. Reindollar, and A. Usheva (2006)
Nucleic Acids Res. 34, 3279-3287
   Abstract »    Full Text »    PDF »
GCUNC-45 Is a Novel Regulator for the Progesterone Receptor/hsp90 Chaperoning Pathway..
A. Chadli, J. D. Graham, M. G. Abel, T. A. Jackson, D. F. Gordon, W. M. Wood, S. J. Felts, K. B. Horwitz, and D. Toft (2006)
Mol. Cell. Biol. 26, 1722-1730
   Abstract »    Full Text »    PDF »
Identification of Candidate Regulators of Embryonic Stem Cell Differentiation by Comparative Phosphoprotein Affinity Profiling.
L. G. Puente, D. J. Borris, J.-F. Carriere, J. F. Kelly, and L. A. Megeney (2006)
Mol. Cell. Proteomics 5, 57-67
   Abstract »    Full Text »    PDF »
CHIP (Carboxyl Terminus of Hsc70-Interacting Protein) Promotes Basal and Geldanamycin-Induced Degradation of Estrogen Receptor-{alpha}.
M. Fan, A. Park, and K. P. Nephew (2005)
Mol. Endocrinol. 19, 2901-2914
   Abstract »    Full Text »    PDF »
The DnaJ-Related Factor Mrj Interacts with Nuclear Factor of Activated T Cells c3 and Mediates Transcriptional Repression through Class II Histone Deacetylase Recruitment.
Y.-S. Dai, J. Xu, and J. D. Molkentin (2005)
Mol. Cell. Biol. 25, 9936-9948
   Abstract »    Full Text »    PDF »
Repression of Interleukin-5 Transcription by the Glucocorticoid Receptor Targets GATA3 Signaling and Involves Histone Deacetylase Recruitment.
Y.-K. Jee, J. Gilmour, A. Kelly, H. Bowen, D. Richards, C. Soh, P. Smith, C. Hawrylowicz, D. Cousins, T. Lee, et al. (2005)
J. Biol. Chem. 280, 23243-23250
   Abstract »    Full Text »    PDF »
Hsp90 and environmental impacts on epigenetic states: a model for the trans-generational effects of diethylstibesterol on uterine development and cancer.
D. M. Ruden, L. Xiao, M. D. Garfinkel, and X. Lu (2005)
Hum. Mol. Genet. 14, R149-R155
   Abstract »    Full Text »    PDF »
Ku Is a Novel Transcriptional Recycling Coactivator of the Androgen Receptor in Prostate Cancer Cells.
G. L. Mayeur, W.-J. Kung, A. Martinez, C. Izumiya, D. J. Chen, and H.-J. Kung (2005)
J. Biol. Chem. 280, 10827-10833
   Abstract »    Full Text »    PDF »
Ligand-Specific Dynamics of the Progesterone Receptor in Living Cells and during Chromatin Remodeling In Vitro.
G. V. Rayasam, C. Elbi, D. A. Walker, R. Wolford, T. M. Fletcher, D. P. Edwards, and G. L. Hager (2005)
Mol. Cell. Biol. 25, 2406-2418
   Abstract »    Full Text »    PDF »
Regulation of coactivator complex assembly and function by protein arginine methylation and demethylimination.
Y.-H. Lee, S. A. Coonrod, W. L. Kraus, M. A. Jelinek, and M. R. Stallcup (2005)
PNAS 102, 3611-3616
   Abstract »    Full Text »    PDF »
Effect of torsinA on membrane proteins reveals a loss of function and a dominant-negative phenotype of the dystonia-associated {Delta}E-torsinA mutant.
G. E. Torres, A. L. Sweeney, J.-M. Beaulieu, P. Shashidharan, and M. G. Caron (2004)
PNAS 101, 15650-15655
   Abstract »    Full Text »    PDF »
Dynamic Control of Nuclear Receptor Transcription.
A. M. Fowler and E. T. Alarid (2004)
Sci. STKE 2004, pe51
   Abstract »    Full Text »    PDF »
The Interaction between Sgt1p and Skp1p Is Regulated by HSP90 Chaperones and Is Required for Proper CBF3 Assembly.
L. B. Lingelbach and K. B. Kaplan (2004)
Mol. Cell. Biol. 24, 8938-8950
   Abstract »    Full Text »    PDF »
Attenuation of estrogen receptor {alpha}-mediated transcription through estrogen-stimulated recruitment of a negative elongation factor.
S. E. Aiyar, J.-l. Sun, A. L. Blair, C. A. Moskaluk, Y.-z. Lu, Q.-n. Ye, Y. Yamaguchi, A. Mukherjee, D.-m. Ren, H. Handa, et al. (2004)
Genes & Dev. 18, 2134-2146
   Abstract »    Full Text »    PDF »
Coactivator AIB1 links estrogen receptor transcriptional activity and stability.
W. Shao, E. K. Keeton, D. P. McDonnell, and M. Brown (2004)
PNAS 101, 11599-11604
   Abstract »    Full Text »    PDF »
Altered Hsp90 function in cancer: A unique therapeutic opportunity.
R. Bagatell and L. Whitesell (2004)
Mol. Cancer Ther. 3, 1021-1030
   Abstract »    Full Text »    PDF »
Global Nature of Dynamic Protein-Chromatin Interactions In Vivo: Three-Dimensional Genome Scanning and Dynamic Interaction Networks of Chromatin Proteins.
R. D. Phair, P. Scaffidi, C. Elbi, J. Vecerova, A. Dey, K. Ozato, D. T. Brown, G. Hager, M. Bustin, and T. Misteli (2004)
Mol. Cell. Biol. 24, 6393-6402
   Abstract »    Full Text »    PDF »
Progesterone Receptor Deficient in Chromatin Binding Has an Altered Cellular State.
J. Botos, W. Xian, D. F. Smith, and C. L. Smith (2004)
J. Biol. Chem. 279, 15231-15239
   Abstract »    Full Text »    PDF »
Rapid Glucocorticoid Receptor Exchange at a Promoter Is Coupled to Transcription and Regulated by Chaperones and Proteasomes.
D. A. Stavreva, W. G. Muller, G. L. Hager, C. L. Smith, and J. G. McNally (2004)
Mol. Cell. Biol. 24, 2682-2697
   Abstract »    Full Text »    PDF »
Molecular chaperones function as steroid receptor nuclear mobility factors.
C. Elbi, D. A. Walker, G. Romero, W. P. Sullivan, D. O. Toft, G. L. Hager, and D. B. DeFranco (2004)
PNAS 101, 2876-2881
   Abstract »    Full Text »    PDF »
Agonist-Activated Glucocorticoid Receptor Inhibits Binding of Heat Shock Factor 1 to the Heat Shock Protein 70 Promoter in Vivo.
S. A. Wadekar, D. Li, and E. R. Sanchez (2004)
Mol. Endocrinol. 18, 500-508
   Abstract »    Full Text »    PDF »
Molecular determinants of responses to myocardial ischemia/reperfusion injury: focus on hypoxia-inducible and heat shock factors.
N. C Chi and J. S Karliner (2004)
Cardiovasc Res 61, 437-447
   Abstract »    Full Text »    PDF »
The Hsp90 Cochaperone p23 Is the Limiting Component of the Multiprotein Hsp90/Hsp70-based Chaperone System in Vivo Where It Acts to Stabilize the Client Protein{middle dot}Hsp90 Complex.
Y. Morishima, K. C. Kanelakis, P. J. M. Murphy, E. R. Lowe, G. J. Jenkins, Y. Osawa, R. K. Sunahara, and W. B. Pratt (2003)
J. Biol. Chem. 278, 48754-48763
   Abstract »    Full Text »    PDF »
Novel Activation Step Required for Transcriptional Competence of Progesterone Receptor on Chromatin Templates.
V. G. Thackray, D. O. Toft, and S. K. Nordeen (2003)
Mol. Endocrinol. 17, 2543-2553
   Abstract »    Full Text »    PDF »
GDP-Mannose 3',5'-Epimerase Forms GDP-L-gulose, a Putative Intermediate for the de Novo Biosynthesis of Vitamin C in Plants.
B. A. Wolucka and M. Van Montagu (2003)
J. Biol. Chem. 278, 47483-47490
   Abstract »    Full Text »    PDF »
The Cochaperone Bag-1L Enhances Androgen Receptor Action via Interaction with the NH2-Terminal Region of the Receptor.
L. Shatkina, S. Mink, H. Rogatsch, H. Klocker, G. Langer, A. Nestl, and A. C. B. Cato (2003)
Mol. Cell. Biol. 23, 7189-7197
   Abstract »    Full Text »    PDF »
Activation Functions 1 and 2 of Nuclear Receptors: Molecular Strategies for Transcriptional Activation.
A. Warnmark, E. Treuter, A. P. H. Wright, and J.-A. Gustafsson (2003)
Mol. Endocrinol. 17, 1901-1909
   Abstract »    Full Text »    PDF »
Nuclear Export of the Glucocorticoid Receptor Is Accelerated by Cell Fusion-dependent Release of Calreticulin.
R. F. Walther, C. Lamprecht, A. Ridsdale, I. Groulx, S. Lee, Y. A. Lefebvre, and R. J. G. Hache (2003)
J. Biol. Chem. 278, 37858-37864
   Abstract »    Full Text »    PDF »
Genetic Dissection of p23, an Hsp90 Cochaperone, Reveals a Distinct Surface Involved in Estrogen Receptor Signaling.
E. Oxelmark, R. Knoblauch, S. Arnal, L. F. Su, M. Schapira, and M. J. Garabedian (2003)
J. Biol. Chem. 278, 36547-36555
   Abstract »    Full Text »    PDF »
Heat and Heavy Metal Stress Synergize to Mediate Transcriptional Hyperactivation by Metal-responsive Transcription Factor MTF-1.
N. Saydam, F. Steiner, O. Georgiev, and W. Schaffner (2003)
J. Biol. Chem. 278, 31879-31883
   Abstract »    Full Text »    PDF »
The Interplay between the Glucocorticoid Receptor and Nuclear Factor-{kappa}B or Activator Protein-1: Molecular Mechanisms for Gene Repression.
K. De Bosscher, W. Vanden Berghe, and G. Haegeman (2003)
Endocr. Rev. 24, 488-522
   Abstract »    Full Text »    PDF »
Functional Interaction of the DNA-binding Transcription Factor Sp1 through Its DNA-binding Domain with the Histone Chaperone TAF-I.
T. Suzuki, S. Muto, S. Miyamoto, K. Aizawa, M. Horikoshi, and R. Nagai (2003)
J. Biol. Chem. 278, 28758-28764
   Abstract »    Full Text »    PDF »
Essential Role of the Unusual DNA-binding Motif of BAG-1 for Inhibition of the Glucocorticoid Receptor.
U. Schmidt, G. M. Wochnik, M. C. Rosenhagen, J. C. Young, F. U. Hartl, F. Holsboer, and T. Rein (2003)
J. Biol. Chem. 278, 4926-4931
   Abstract »    Full Text »    PDF »
The Influence of ATP and p23 on the Conformation of hsp90.
W. P. Sullivan, B. A. L. Owen, and D. O. Toft (2002)
J. Biol. Chem. 277, 45942-45948
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)