This Article
Right arrow Full Text (PDF)
Right arrow An author's correction has been published
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lin, B. C.
Right arrow Articles by Privalsky, M. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lin, B. C.
Right arrow Articles by Privalsky, M. L.

 Previous Article  |  Next Article 

Mol. Cell. Biol., Oct 1997, 6131-6138, Vol 17, No. 10
Copyright © 1997, American Society for Microbiology

A conformational switch in nuclear hormone receptors is involved in coupling hormone binding to corepressor release

BC Lin, SH Hong, S Krig, SM Yoh and ML Privalsky
Division of Biological Sciences, University of California at Davis, 95616, USA.

Nuclear hormone receptors are ligand-regulated transcription factors that modulate gene expression in response to small, hydrophobic hormones, such as retinoic acid and thyroid hormone. The thyroid hormone and retinoic acid receptors typically repress transcription in the absence of hormone and activate it in the presence of hormone. Transcriptional repression is mediated, in part, through the ability of these receptors to physically associate with ancillary polypeptides called corepressors. We wished to understand the mechanism by which corepressors are recruited to unliganded nuclear hormone receptors and are released on the binding of hormone. We report here that an alpha- helical domain located at the thyroid hormone receptor C terminus appears to undergo a hormone-induced conformational change required for release of corepressor and that amino acid substitutions that abrogate this conformational change can impair or prevent corepressor release. In contrast, retinoid X receptors appear neither to undergo an equivalent conformational alteration in their C termini nor to release corepressor in response to cognate hormone, consistent with the distinct transcriptional regulatory properties displayed by this class of receptors.


This article has been cited by other articles:

  • Putcha, B.-D. K., Fernandez, E. J. (2009). Direct Interdomain Interactions Can Mediate Allosterism in the Thyroid Receptor. J. Biol. Chem. 284: 22517-22524 [Abstract] [Full Text]  
  • Privalsky, M. L., Lee, S., Hahm, J. B., Young, B. M., Fong, R. N. G., Chan, I. H. (2009). The p160 Coactivator PAS-B Motif Stabilizes Nuclear Receptor Binding and Contributes to Isoform-specific Regulation by Thyroid Hormone Receptors. J. Biol. Chem. 284: 19554-19563 [Abstract] [Full Text]  
  • Sanchez-Martinez, R., Zambrano, A., Castillo, A. I., Aranda, A. (2008). Vitamin D-Dependent Recruitment of Corepressors to Vitamin D/Retinoid X Receptor Heterodimers. Mol. Cell. Biol. 28: 3817-3829 [Abstract] [Full Text]  
  • Mettu, N. B., Stanley, T. B., Dwyer, M. A., Jansen, M. S., Allen, J. E., Hall, J. M., McDonnell, D. P. (2007). The Nuclear Receptor-Coactivator Interaction Surface as a Target for Peptide Antagonists of the Peroxisome Proliferator-Activated Receptors. Mol. Endocrinol. 21: 2361-2377 [Abstract] [Full Text]  
  • Wu, S. Y., Cohen, R. N., Simsek, E., Senses, D. A., Yar, N. E., Grasberger, H., Noel, J., Refetoff, S., Weiss, R. E. (2006). A Novel Thyroid Hormone Receptor-{beta} Mutation That Fails to Bind Nuclear Receptor Corepressor in a Patient as an Apparent Cause of Severe, Predominantly Pituitary Resistance to Thyroid Hormone. J. Clin. Endocrinol. Metab. 91: 1887-1895 [Abstract] [Full Text]  
  • Wan, W., Farboud, B., Privalsky, M. L. (2005). Pituitary Resistance to Thyroid Hormone Syndrome Is Associated with T3 Receptor Mutants that Selectively Impair {beta}2 Isoform Function. Mol. Endocrinol. 19: 1529-1542 [Abstract] [Full Text]  
  • Farboud, B., Privalsky, M. L. (2004). Retinoic Acid Receptor-{alpha} Is Stabilized in a Repressive State by Its C-Terminal, Isotype-Specific F Domain. Mol. Endocrinol. 18: 2839-2853 [Abstract] [Full Text]  
  • Benko, S., Love, J. D., Beladi, M., Schwabe, J. W. R., Nagy, L. (2003). Molecular Determinants of the Balance between Co-repressor and Co-activator Recruitment to the Retinoic Acid Receptor. J. Biol. Chem. 278: 43797-43806 [Abstract] [Full Text]  
  • Farboud, B., Hauksdottir, H., Wu, Y., Privalsky, M. L. (2003). Isotype-Restricted Corepressor Recruitment: a Constitutively Closed Helix 12 Conformation in Retinoic Acid Receptors {beta} and {gamma} Interferes with Corepressor Recruitment and Prevents Transcriptional Repression. Mol. Cell. Biol. 23: 2844-2858 [Abstract] [Full Text]  
  • Hauksdottir, H., Farboud, B., Privalsky, M. L. (2003). Retinoic Acid Receptors {beta} and {gamma} Do Not Repress, But Instead Activate Target Gene Transcription in Both the Absence and Presence of Hormone Ligand. Mol. Endocrinol. 17: 373-385 [Abstract] [Full Text]  
  • Torres-Padilla, M. E., Sladek, F. M., Weiss, M. C. (2002). Developmentally Regulated N-terminal Variants of the Nuclear Receptor Hepatocyte Nuclear Factor 4alpha Mediate Multiple Interactions through Coactivator and Corepressor-Histone Deacetylase Complexes. J. Biol. Chem. 277: 44677-44687 [Abstract] [Full Text]  
  • Love, J. D., Gooch, J. T., Benko, S., Li, C., Nagy, L., Chatterjee, V. K. K., Evans, R. M., Schwabe, J. W. R. (2002). The Structural Basis for the Specificity of Retinoid-X Receptor-selective Agonists: New Insights Into the Role of Helix H12. J. Biol. Chem. 277: 11385-11391 [Abstract] [Full Text]  
  • Marimuthu, A., Feng, W., Tagami, T., Nguyen, H., Jameson, J. L., Fletterick, R. J., Baxter, J. D., West, B. L. (2002). TR Surfaces and Conformations Required to Bind Nuclear Receptor Corepressor. Mol. Endocrinol. 16: 271-286 [Abstract] [Full Text]  
  • Hong, S.-H., Yang, Z., Privalsky, M. L. (2001). Arsenic Trioxide Is a Potent Inhibitor of the Interaction of SMRT Corepressor with Its Transcription Factor Partners, Including the PML-Retinoic Acid Receptor {alpha} Oncoprotein Found in Human Acute Promyelocytic Leukemia. Mol. Cell. Biol. 21: 7172-7182 [Abstract] [Full Text]  
  • Aranda, A., Pascual, A. (2001). Nuclear Hormone Receptors and Gene Expression. Physiol. Rev. 81: 1269-1304 [Abstract] [Full Text]  
  • Washburn, B. K., Esposito, R. E. (2001). Identification of the Sin3-Binding Site in Ume6 Defines a Two-Step Process for Conversion of Ume6 from a Transcriptional Repressor to an Activator in Yeast. Mol. Cell. Biol. 21: 2057-2069 [Abstract] [Full Text]  
  • Cohen, R. N., Putney, A., Wondisford, F. E., Hollenberg, A. N. (2000). The Nuclear Corepressors Recognize Distinct Nuclear Receptor Complexes. Mol. Endocrinol. 14: 900-914 [Abstract] [Full Text]  
  • Renaud, J.-P., Harris, J. M., Downes, M., Burke, L. J., Muscat, G. E .O. (2000). Structure-Function Analysis of the Rev-erbA and RVR Ligand-Binding Domains Reveals a Large Hydrophobic Surface That Mediates Corepressor Binding and a Ligand Cavity Occupied by Side Chains. Mol. Endocrinol. 14: 700-717 [Abstract] [Full Text]  
  • Robyr, D., Wolffe, A. P., Wahli, W. (2000). Nuclear Hormone Receptor Coregulators In Action: Diversity For Shared Tasks. Mol. Endocrinol. 14: 329-347 [Full Text]  
  • Gurnell, M., Wentworth, J. M., Agostini, M., Adams, M., Collingwood, T. N., Provenzano, C., Browne, P. O., Rajanayagam, O., Burris, T. P., Schwabe, J. W., Lazar, M. A., Chatterjee, V. K. K. (2000). A Dominant-negative Peroxisome Proliferator-activated Receptor gamma (PPARgamma ) Mutant Is a Constitutive Repressor and Inhibits PPARgamma -mediated Adipogenesis. J. Biol. Chem. 275: 5754-5759 [Abstract] [Full Text]  
  • Yang, Z., Hong, S.-H., Privalsky, M. L. (1999). Transcriptional Anti-repression. THYROID HORMONE RECEPTOR beta -2 RECRUITS SMRT COREPRESSOR BUT INTERFERES WITH SUBSEQUENT ASSEMBLY OF A FUNCTIONAL COREPRESSOR COMPLEX. J. Biol. Chem. 274: 37131-37138 [Abstract] [Full Text]  
  • New, (1999). Resistance to Several Steroids in Two Sisters. J. Clin. Endocrinol. Metab. 84: 4454-4464 [Abstract] [Full Text]  
  • Sladek, F. M., Ruse, M. D. Jr., Nepomuceno, L., Huang, S.-M., Stallcup, M. R. (1999). Modulation of Transcriptional Activation and Coactivator Interaction by a Splicing Variation in the F Domain of Nuclear Receptor Hepatocyte Nuclear Factor 4alpha 1. Mol. Cell. Biol. 19: 6509-6522 [Abstract] [Full Text]  
  • Zhang, J., Hu, X., Lazar, M. A. (1999). A Novel Role for Helix 12 of Retinoid X Receptor in Regulating Repression. Mol. Cell. Biol. 19: 6448-6457 [Abstract] [Full Text]  
  • Redner, R. L., Wang, J., Liu, J. M. (1999). Chromatin Remodeling and Leukemia: New Therapeutic Paradigms. Blood 94: 417-428 [Full Text]  
  • Dressel, U., Thormeyer, D., Altincicek, B., Paululat, A., Eggert, M., Schneider, S., Tenbaum, S. P., Renkawitz, R., Baniahmad, A. (1999). Alien, a Highly Conserved Protein with Characteristics of a Corepressor for Members of the Nuclear Hormone Receptor Superfamily. Mol. Cell. Biol. 19: 3383-3394 [Abstract] [Full Text]  
  • Hong, S.-H., Privalsky, M. L. (1999). Retinoid Isomers Differ in the Ability to Induce Release of SMRT Corepressor from Retinoic Acid Receptor-alpha. J. Biol. Chem. 274: 2885-2892 [Abstract] [Full Text]  
  • Tagami, T., Gu, W.-X., Peairs, P. T., West, B. L., Jameson, J. L. (1998). A Novel Natural Mutation in the Thyroid Hormone Receptor Defines a Dual Functional Domain That Exchanges Nuclear Receptor Corepressors and Coactivators. Mol. Endocrinol. 12: 1888-1902 [Abstract] [Full Text]  
  • Wong, C.-W., Privalsky, M. L. (1998). Components of the SMRT Corepressor Complex Exhibit Distinctive Interactions with the POZ Domain Oncoproteins PLZF, PLZF-RARalpha , and BCL-6. J. Biol. Chem. 273: 27695-27702 [Abstract] [Full Text]  
  • Wong, C.-W., Privalsky, M. L. (1998). Transcriptional Silencing Is Defined by Isoform- and Heterodimer-Specific Interactions between Nuclear Hormone Receptors and Corepressors. Mol. Cell. Biol. 18: 5724-5733 [Abstract] [Full Text]  
  • Hong, S.-H., Wong, C.-W., Privalsky, M. L. (1998). Signaling by Tyrosine Kinases Negatively Regulates the Interaction between Transcription Factors and SMRT (Silencing Mediator of Retinoic Acid and Thyroid Hormone Receptor) Corepressor. Mol. Endocrinol. 12: 1161-1171 [Abstract] [Full Text]  
  • Chinpaisal, C., Lee, C.-H., Wei, L.-N. (1998). Mechanisms of the Mouse Orphan Nuclear Receptor TR2-11-mediated Gene Suppression. J. Biol. Chem. 273: 18077-18085 [Abstract] [Full Text]  
  • Zhang, Y., Yin, L., Hillgartner, F. B. (2001). Thyroid Hormone Stimulates Acetyl-CoA Carboxylase-alpha Transcription in Hepatocytes by Modulating the Composition of Nuclear Receptor Complexes Bound to a Thyroid Hormone Response Element. J. Biol. Chem. 276: 974-983 [Abstract] [Full Text]  
  • Yoh, S. M., Privalsky, M. L. (2001). Transcriptional Repression by Thyroid Hormone Receptors. A ROLE FOR RECEPTOR HOMODIMERS IN THE RECRUITMENT OF SMRT COREPRESSOR. J. Biol. Chem. 276: 16857-16867 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»