This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 Hu, X.
Right arrow Articles by Lazar, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hu, X.
Right arrow Articles by Lazar, M. A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 2001, p. 1747-1758, Vol. 21, No. 5
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.5.1747-1758.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Determinants of CoRNR-Dependent Repression Complex Assembly on Nuclear Hormone Receptors

Xiao Hu, Yun Li, and Mitchell A. Lazar*

Division of Endocrinology, Diabetes, and Metabolism, Departments of Medicine and Genetics, and The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Received 8 September 2000/Returned for modification 6 October 2000/Accepted 6 December 2000

Ligand-dependent exchange of coactivators and corepressors is the fundamental regulator of nuclear hormone receptor (NHR) function. The interaction surfaces of coactivators and corepressors are similar but distinct enough to allow the ligand to function as a switch. Multiple NHRs share features that allow corepressor binding, and each of two distinct corepressors (N-CoR and SMRT) contains two similar CoRNR motifs that interact with NHRs. Here we report that the specificity of corepressor-NHR interaction is determined by the individual NHR interacting with specific CoRNR boxes within a preferred corepressor. First, receptors have distinct preferences for CoRNR1 versus CoRNR2. For example, the retinoic acid receptor binds CoRNR1, while RXR interacts almost exclusively with CoRNR2. Second, the NHR preference for N-CoR or SMRT is due to differences in CoRNR1 but not CoRNR2. Moreover, within a single corepressor, affinity for different NHRs is determined by distinct regions flanking CoRNR1. The highly specific determinants of NHR-corepressor interaction and preference suggest that repression is regulated by the permissibility of selected receptor-CoRNR-corepressor combinations. Interestingly, different NHR surfaces contribute to binding of CoRNR1 and CoRNR2, suggesting a model to explain corepressor binding to NHR heterodimers.

* Corresponding author. Mailing address: University of Pennsylvania School of Medicine, 611 CRB, 415 Curie Blvd., Philadelphia, PA 19104-6149. Phone: (215) 898-0198. Fax: (215) 898-5408. E-mail: lazar{at}mail.med.upenn.edu.

Molecular and Cellular Biology, March 2001, p. 1747-1758, Vol. 21, No. 5
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.5.1747-1758.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • De Amicis, F., Zupo, S., Panno, M. L., Malivindi, R., Giordano, F., Barone, I., Mauro, L., Fuqua, S. A. W., Ando, S. (2009). Progesterone Receptor B Recruits a Repressor Complex to a Half-PRE Site of the Estrogen Receptor {alpha} Gene Promoter. Mol. Endocrinol. 23: 454-465 [Abstract] [Full Text]  
  • Kim, J. Y., Son, Y. L., Lee, Y. C. (2009). Involvement of SMRT Corepressor in Transcriptional Repression by the Vitamin D Receptor. Mol. Endocrinol. 23: 251-264 [Abstract] [Full Text]  
  • Song, L.-N., Gelmann, E. P. (2008). Silencing Mediator for Retinoid and Thyroid Hormone Receptor and Nuclear Receptor Corepressor Attenuate Transcriptional Activation by the {beta}-Catenin-TCF4 Complex. J. Biol. Chem. 283: 25988-25999 [Abstract] [Full Text]  
  • Liu, M. H., Li, J., Shen, P., Husna, B., Tai, E. S., Yong, E. L. (2008). A Natural Polymorphism in Peroxisome Proliferator-Activated Receptor-{alpha} Hinge Region Attenuates Transcription due to Defective Release of Nuclear Receptor Corepressor from Chromatin. Mol. Endocrinol. 22: 1078-1092 [Abstract] [Full Text]  
  • Kim, J. Y., Park, O. G., Lee, J. W., Lee, Y. C. (2007). One- plus Two-hybrid System, a Novel Yeast Genetic Selection for Specific Missense Mutations Disrupting Protein/Protein Interactions. Mol. Cell. Proteomics 6: 1727-1740 [Abstract] [Full Text]  
  • Jonas, B. A., Varlakhanova, N., Hayakawa, F., Goodson, M., Privalsky, M. L. (2007). Response of SMRT (Silencing Mediator of Retinoic Acid and Thyroid Hormone Receptor) and N-CoR (Nuclear Receptor Corepressor) Corepressors to Mitogen-Activated Protein Kinase Kinase Kinase Cascades Is Determined by Alternative mRNA Splicing. Mol. Endocrinol. 21: 1924-1939 [Abstract] [Full Text]  
  • Jeyakumar, M., Liu, X.-f., Erdjument-Bromage, H., Tempst, P., Bagchi, M. K. (2007). Phosphorylation of Thyroid Hormone Receptor-associated Nuclear Receptor Corepressor Holocomplex by the DNA-dependent Protein Kinase Enhances Its Histone Deacetylase Activity. J. Biol. Chem. 282: 9312-9322 [Abstract] [Full Text]  
  • Wang, J., Yin, L., Lazar, M. A. (2006). The Orphan Nuclear Receptor Rev-erb{alpha} Regulates Circadian Expression of Plasminogen Activator Inhibitor Type 1. J. Biol. Chem. 281: 33842-33848 [Abstract] [Full Text]  
  • Wu, Y., Kawate, H., Ohnaka, K., Nawata, H., Takayanagi, R. (2006). Nuclear Compartmentalization of N-CoR and Its Interactions with Steroid Receptors.. Mol. Cell. Biol. 26: 6633-6655 [Abstract] [Full Text]  
  • Stossi, F., Likhite, V. S., Katzenellenbogen, J. A., Katzenellenbogen, B. S. (2006). Estrogen-occupied Estrogen Receptor Represses Cyclin G2 Gene Expression and Recruits a Repressor Complex at the Cyclin G2 Promoter. J. Biol. Chem. 281: 16272-16278 [Abstract] [Full Text]  
  • Gao, Z., He, Q., Peng, B., Chiao, P. J., Ye, J. (2006). Regulation of Nuclear Translocation of HDAC3 by I{kappa}B{alpha} Is Required for Tumor Necrosis Factor Inhibition of Peroxisome Proliferator-activated Receptor {gamma} Function. J. Biol. Chem. 281: 4540-4547 [Abstract] [Full Text]  
  • Nagpal, S., Na, S., Rathnachalam, R. (2005). Noncalcemic Actions of Vitamin D Receptor Ligands. Endocr. Rev. 26: 662-687 [Abstract] [Full Text]  
  • Voss, T. C., Demarco, I. A., Booker, C. F., Day, R. N. (2005). Functional interactions with Pit-1 reorganize co-repressor complexes in the living cell nucleus. J. Cell Sci. 118: 3277-3288 [Abstract] [Full Text]  
  • Ishizuka, T., Lazar, M. A. (2005). The Nuclear Receptor Corepressor Deacetylase Activating Domain Is Essential for Repression by Thyroid Hormone Receptor. Mol. Endocrinol. 19: 1443-1451 [Abstract] [Full Text]  
  • Yin, L., Lazar, M. A. (2005). The Orphan Nuclear Receptor Rev-erb{alpha} Recruits the N-CoR/Histone Deacetylase 3 Corepressor to Regulate the Circadian Bmal1 Gene. Mol. Endocrinol. 19: 1452-1459 [Abstract] [Full Text]  
  • Wang, D., Simons, S. S. Jr. (2005). Corepressor Binding to Progesterone and Glucocorticoid Receptors Involves the Activation Function-1 Domain and Is Inhibited by Molybdate. Mol. Endocrinol. 19: 1483-1500 [Abstract] [Full Text]  
  • Moore, J. M. R., Guy, R. K. (2005). Coregulator Interactions with the Thyroid Hormone Receptor. Mol. Cell. Proteomics 4: 475-482 [Abstract] [Full Text]  
  • Goodson, M. L., Jonas, B. A., Privalsky, M. L. (2005). Alternative mRNA Splicing of SMRT Creates Functional Diversity by Generating Corepressor Isoforms with Different Affinities for Different Nuclear Receptors. J. Biol. Chem. 280: 7493-7503 [Abstract] [Full Text]  
  • Park, S.-E., Xu, J., Frolova, A., Liao, L., O'Malley, B. W., Katzenellenbogen, B. S. (2005). Genetic Deletion of the Repressor of Estrogen Receptor Activity (REA) Enhances the Response to Estrogen in Target Tissues In Vivo. Mol. Cell. Biol. 25: 1989-1999 [Abstract] [Full Text]  
  • Guan, H.-P., Ishizuka, T., Chui, P. C., Lehrke, M., Lazar, M. A. (2005). Corepressors selectively control the transcriptional activity of PPAR{gamma} in adipocytes. Genes Dev. 19: 453-461 [Abstract] [Full Text]  
  • Malartre, M., Short, S., Sharpe, C. (2004). Alternative splicing generates multiple SMRT transcripts encoding conserved repressor domains linked to variable transcription factor interaction domains. Nucleic Acids Res 32: 4676-4686 [Abstract] [Full Text]  
  • Wang, Q., Blackford, J. A. Jr., Song, L.-N., Huang, Y., Cho, S., Simons, S. S. Jr. (2004). Equilibrium Interactions of Corepressors and Coactivators with Agonist and Antagonist Complexes of Glucocorticoid Receptors. Mol. Endocrinol. 18: 1376-1395 [Abstract] [Full Text]  
  • Castillo, A. I., Sanchez-Martinez, R., Moreno, J. L., Martinez-Iglesias, O. A., Palacios, D., Aranda, A. (2004). A Permissive Retinoid X Receptor/Thyroid Hormone Receptor Heterodimer Allows Stimulation of Prolactin Gene Transcription by Thyroid Hormone and 9-cis-Retinoic Acid. Mol. Cell. Biol. 24: 502-513 [Abstract] [Full Text]  
  • Fu, M., Rao, M., Wang, C., Sakamaki, T., Wang, J., Di Vizio, D., Zhang, X., Albanese, C., Balk, S., Chang, C., Fan, S., Rosen, E., Palvimo, J. J., Janne, O. A., Muratoglu, S., Avantaggiati, M. L., Pestell, R. G. (2003). Acetylation of Androgen Receptor Enhances Coactivator Binding and Promotes Prostate Cancer Cell Growth. Mol. Cell. Biol. 23: 8563-8575 [Abstract] [Full Text]  
  • Ishizuka, T., Lazar, M. A. (2003). The N-CoR/Histone Deacetylase 3 Complex Is Required for Repression by Thyroid Hormone Receptor. Mol. Cell. Biol. 23: 5122-5131 [Abstract] [Full Text]  
  • Hu, X., Li, S., Wu, J., Xia, C., Lala, D. S. (2003). Liver X Receptors Interact with Corepressors to Regulate Gene Expression. Mol. Endocrinol. 17: 1019-1026 [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]  
  • Olswang, Y., Blum, B., Cassuto, H., Cohen, H., Biberman, Y., Hanson, R. W., Reshef, L. (2003). Glucocorticoids Repress Transcription of Phosphoenolpyruvate Carboxykinase (GTP) Gene in Adipocytes by Inhibiting Its C/EBP-mediated Activation. J. Biol. Chem. 278: 12929-12936 [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]  
  • Rajendran, R. R., Nye, A. C., Frasor, J., Balsara, R. D., Martini, P. G. V., Katzenellenbogen, B. S. (2003). Regulation of Nuclear Receptor Transcriptional Activity by a Novel DEAD Box RNA Helicase (DP97). J. Biol. Chem. 278: 4628-4638 [Abstract] [Full Text]  
  • Makowski, A., Brzostek, S., Cohen, R. N., Hollenberg, A. N. (2003). Determination of Nuclear Receptor Corepressor Interactions with the Thyroid Hormone Receptor. Mol. Endocrinol. 17: 273-286 [Abstract] [Full Text]  
  • Borgius, L. J., Steffensen, K. R., Gustafsson, J.-A., Treuter, E. (2002). Glucocorticoid Signaling Is Perturbed by the Atypical Orphan Receptor and Corepressor SHP. J. Biol. Chem. 277: 49761-49766 [Abstract] [Full Text]  
  • Takeshita, A., Taguchi, M., Koibuchi, N., Ozawa, Y. (2002). Putative Role of the Orphan Nuclear Receptor SXR (Steroid and Xenobiotic Receptor) in the Mechanism of CYP3A4 Inhibition by Xenobiotics. J. Biol. Chem. 277: 32453-32458 [Abstract] [Full Text]  
  • Dussault, I., Lin, M., Hollister, K., Fan, M., Termini, J., Sherman, M. A., Forman, B. M. (2002). A Structural Model of the Constitutive Androstane Receptor Defines Novel Interactions That Mediate Ligand-Independent Activity. Mol. Cell. Biol. 22: 5270-5280 [Abstract] [Full Text]  
  • Fu, M., Wang, C., Wang, J., Zhang, X., Sakamaki, T., Yeung, Y. G., Chang, C., Hopp, T., Fuqua, S. A. W., Jaffray, E., Hay, R. T., Palvimo, J. J., Janne, O. A., Pestell, R. G. (2002). Androgen Receptor Acetylation Governs trans Activation and MEKK1-Induced Apoptosis without Affecting In Vitro Sumoylation and trans-Repression Function. Mol. Cell. Biol. 22: 3373-3388 [Abstract] [Full Text]  
  • Ghosh, J. C., Yang, X., Zhang, A., Lambert, M. H., Li, H., Xu, H. E., Chen, J. D. (2002). Interactions that determine the assembly of a retinoid X receptor/corepressor complex. Proc. Natl. Acad. Sci. USA 99: 5842-5847 [Abstract] [Full Text]  
  • Ruse, M. D. Jr., Privalsky, M. L., Sladek, F. M. (2002). Competitive Cofactor Recruitment by Orphan Receptor Hepatocyte Nuclear Factor 4{alpha}1: Modulation by the F Domain. Mol. Cell. Biol. 22: 1626-1638 [Abstract] [Full Text]  
  • Klinge, C. M., Jernigan, S. C., Risinger, K. E. (2002). The Agonist Activity of Tamoxifen Is Inhibited by the Short Heterodimer Partner Orphan Nuclear Receptor in Human Endometrial Cancer Cells. Endocrinology 143: 853-867 [Abstract] [Full Text]  
  • Jepsen, K., Rosenfeld, M. G. (2002). Biological roles and mechanistic actions of co-repressor complexes. J. Cell Sci. 115: 689-698 [Abstract] [Full Text]  
  • Ghosh, J. C., Yang, X., Zhang, A., Lambert, M. H., Li, H., Xu, H. E., Chen, J. D. (2002). Interactions that determine the assembly of a retinoid X receptor/corepressor complex. Proc. Natl. Acad. Sci. USA 99: 5842-5847 [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»