help button home button Endocrine Society Molecular Endocrinology ENDO 08 Sessions Library
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
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 arrow Reprints, Permissions and Rights
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Burke, L. J.
Right arrow Articles by Muscat, G. E. O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Burke, L. J.
Right arrow Articles by Muscat, G. E. O.
Molecular Endocrinology 12 (2): 248-262
Copyright © 1998 by The Endocrine Society

Identification and Characterization of a Novel Corepressor Interaction Region in RVR and Rev-erbA{alpha}

Les J. Burke1, Michael Downes1, Vincent Laudet and George E. O. Muscat

University of Queensland (L.J.B., M.D., G.E.O.M.) Centre for Molecular and Cellular Biology Ritchie Research Laboratories Brisbane, 4072, Queensland, Australia
Centre Nationale de la Recherche Scientifique (V.L.) Institut Pasteur Oncologie Moléculaire Lille-France

Rev-erbA{alpha} and RVR are orphan nuclear receptors that function as dominant transcriptional silencers. Ligand-independent repression of transcription by Rev-erbA{alpha} and RVR is mediated by the nuclear receptor corepressors, N-CoR and its variants RIP (RXR interacting protein) 13a and RIP13{Delta}1. The physical association between the corepressors and Rev-erbA{alpha} and RVR is dependent on the presence of a receptor interaction domain (RID) in the N-CoR family. Our previous study demonstrated that the E region of RVR and Rev-erbA{alpha} is necessary and sufficient for the in vivo interaction with the nuclear receptor corepressor, RIP13{Delta}1. The present investigation demonstrates that two corepressor interaction regions, CIR-1 and CIR-2, separated by ~150 amino acids in the E region of RVR, are required for the interaction with N-CoR, RIP13a, and RIP13{Delta}1. The D region is not required for the physical interaction. In contrast, the D and E regions of Rev-erbA{alpha} were necessary for the interaction with the N-CoR and RIP13a-RIDs in vivo, suggesting that RIP13{Delta}1 and N-CoR/RIP13a differentially interact with Rev-erbA{alpha}. Mutagenesis of CIR-1, a novel domain that is highly conserved between RVR and Rev-erbA{alpha}, demonstrated that the N-terminal portion of helix 3 plays a key role and is absolutely necessary for the interaction with RIP13{Delta}1, RIP13a, and N-CoR. The phenylalanine residues, F402 and F441, in RVR and Rev-erbA{alpha}, respectively, were critical residues in supporting corepressor interaction. Cotransfection studies demonstrated that repression of a physiological target, the human Rev-erbA{alpha} promoter, by RVR was significantly impaired by mutation of CIR-1 or deletion of CIR-2. Furthermore, overexpression of either the N-CoR/RIP13a or RIP13{Delta}1-RIDs alleviated RVR-mediated repression of the Rev-erbA{alpha} promoter, demonstrating that corepressor binding mediates the repression of a native target gene by RVR. A minimal region containing juxtapostioned CIR-1 and CIR-2 was sufficient for corepressor binding and transcriptional repression. In conclusion, our study has identified a new corepressor interaction region, CIR-1, in the N terminus of helix 3 in the E region of RVR and Rev-erbA{alpha}, that is required for transcriptional silencing. Furthermore, we provide evidence that CIR-1 and CIR-2 may form a single corepressor interaction interface.




This article has been cited by other articles:


Home page
 Pharmacol. Rev.Home page
G. Benoit, A. Cooney, V. Giguere, H. Ingraham, M. Lazar, G. Muscat, T. Perlmann, J.-P. Renaud, J. Schwabe, F. Sladek, et al.
International Union of Pharmacology. LXVI. Orphan Nuclear Receptors
Pharmacol. Rev., December 1, 2006; 58(4): 798 - 836.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. N. Ramakrishnan, P. Lau, L. J. Burke, and G. E. O. Muscat
Rev-erb{beta} Regulates the Expression of Genes Involved in Lipid Absorption in Skeletal Muscle Cells: EVIDENCE FOR CROSS-TALK BETWEEN ORPHAN NUCLEAR RECEPTORS AND MYOKINES
J. Biol. Chem., March 11, 2005; 280(10): 8651 - 8659.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. L. Goodson, B. A. Jonas, and M. L. Privalsky
Alternative mRNA Splicing of SMRT Creates Functional Diversity by Generating Corepressor Isoforms with Different Affinities for Different Nuclear Receptors
J. Biol. Chem., March 4, 2005; 280(9): 7493 - 7503.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. D. S. A. Wansa, J. M. Harris, G. Yan, P. Ordentlich, and G. E. O. Muscat
The AF-1 Domain of the Orphan Nuclear Receptor NOR-1 Mediates Trans-activation, Coactivator Recruitment, and Activation by the Purine Anti-metabolite 6-Mercaptopurine
J. Biol. Chem., June 27, 2003; 278(27): 24776 - 24790.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. Webb, P. Nguyen, and P. J. Kushner
Differential SERM Effects on Corepressor Binding Dictate ERalpha Activity in Vivo
J. Biol. Chem., February 21, 2003; 278(9): 6912 - 6920.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Raspe, G. Mautino, C. Duval, C. Fontaine, H. Duez, O. Barbier, D. Monte, J. Fruchart, J.-C. Fruchart, and B. Staels
Transcriptional Regulation of Human Rev-erbalpha Gene Expression by the Orphan Nuclear Receptor Retinoic Acid-related Orphan Receptor alpha
J. Biol. Chem., December 13, 2002; 277(51): 49275 - 49281.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Swevers, K. Ito, and K. Iatrou
The BmE75 Nuclear Receptors Function as Dominant Repressors of the Nuclear Receptor BmHR3A
J. Biol. Chem., October 25, 2002; 277(44): 41637 - 41644.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. D. S. A. Wansa, J. M. Harris, and G. E. O. Muscat
The Activation Function-1 Domain of Nur77/NR4A1 Mediates Trans-activation, Cell Specificity, and Coactivator Recruitment
J. Biol. Chem., August 30, 2002; 277(36): 33001 - 33011.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
J. M. Harris, P. Lau, S. L. Chen, and G. E. O. Muscat
Characterization of the Retinoid Orphan-Related Receptor-{alpha} Coactivator Binding Interface: A Structural Basis for Ligand-Independent Transcription
Mol. Endocrinol., May 1, 2002; 16(5): 998 - 1012.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
H. Dotzlaw, U. Moehren, S. Mink, A. C. B. Cato, J. A. Iniguez Lluhi, and A. Baniahmad
The Amino Terminus of the Human AR Is Target for Corepressor Action and Antihormone Agonism
Mol. Endocrinol., April 1, 2002; 16(4): 661 - 673.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
X. Hu, Y. Li, and M. A. Lazar
Determinants of CoRNR-Dependent Repression Complex Assembly on Nuclear Hormone Receptors
Mol. Cell. Biol., March 1, 2001; 21(5): 1747 - 1758.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
P. Webb, C. M. Anderson, C. Valentine, P. Nguyen, A. Marimuthu, B. L. West, J. D. Baxter, and P. J. Kushner
The Nuclear Receptor Corepressor (N-CoR) Contains Three Isoleucine Motifs (I/LXXII) That Serve as Receptor Interaction Domains (IDs)
Mol. Endocrinol., December 1, 2000; 14(12): 1976 - 1985.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
I. P. Torra, V. Tsibulsky, F. Delaunay, R. Saladin, V. Laudet, J.-C. Fruchart, V. Kosykh, and B. Staels
Circadian and Glucocorticoid Regulation of Rev-erb{alpha} Expression in Liver
Endocrinology, October 1, 2000; 141(10): 3799 - 3806.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
P. POLLY, M. HERDICK, U. MOEHREN, A. BANIAHMAD, T. HEINZEL, and C. CARLBERG
VDR-Alien: a novel, DNA-selective vitamin D3 receptor-corepressor partnership
FASEB J, July 1, 2000; 14(10): 1455 - 1463.
[Abstract] [Full Text]

Home page
 Genes Dev.Home page
A. Antebi, W.-H. Yeh, D. Tait, E. M. Hedgecock, and D. L. Riddle
daf-12 encodes a nuclear receptor that regulates the dauer diapause and developmental age in C. elegans
Genes & Dev., June 15, 2000; 14(12): 1512 - 1527.
[Abstract] [Full Text]

Home page
 Mol. Endocrinol.Home page
J.-P. Renaud, J. M. Harris, M. Downes, L. J. Burke, and G. E .O. Muscat
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., May 1, 2000; 14(5): 700 - 717.
[Abstract] [Full Text]

Home page
 Mol. Endocrinol.Home page
K. Busch, B. Martin, A. Baniahmad, J. A. Martial, R. Renkawitz, and M. Muller
Silencing Subdomains of v-ErbA Interact Cooperatively with Corepressors: Involvement of Helices 5/6
Mol. Endocrinol., February 1, 2000; 14(2): 201 - 211.
[Abstract] [Full Text]

Home page
 Endocr. Rev.Home page
V. Giguère
Orphan Nuclear Receptors: From Gene to Function
Endocr. Rev., October 1, 1999; 20(5): 689 - 725.
[Abstract] [Full Text]

Home page
 Mol. Endocrinol.Home page
P. Bailey, M. Downes, P. Lau, J. Harris, S. L. Chen, Y. Hamamori, V. Sartorelli, and G. E. O. Muscat
The Nuclear Receptor Corepressor N-CoR Regulates Differentiation: N-CoR Directly Interacts with MyoD
Mol. Endocrinol., July 1, 1999; 13(7): 1155 - 1168.
[Abstract] [Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1998 by The Endocrine Society