This Article Full Text Full Text (PDF) All Versions of this Article: 18/12/2839    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager NURSA Molecule Pages Link Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Farboud, B. Articles by Privalsky, M. L. Search for Related Content PubMed PubMed Citation Articles by Farboud, B. Articles by Privalsky, M. L.

Retinoic Acid Receptor- Is Stabilized in a Repressive State by Its C-Terminal, Isotype-Specific F Domain

Section of Microbiology, Division of Biological Sciences, University of California at Davis, Davis, California 95616

Address all correspondence and requests for reprints to: Martin L. Privalsky, Section of Microbiology, Division of Biological Sciences, One Shields Avenue, University of California at Davis, Davis, California 95616. E-mail: mlprivalsky{at}ucdavis.edu.

Retinoic acid receptors (RARs) are hormone-regulated transcription factors that play multiple roles in vertebrate development and differentiation. Three isotypes of RARs, , ß, and , are encoded by distinct genetic loci and possess distinct transcriptional properties. Typically, RAR represses target gene transcription in the absence of hormone, whereas RARß and fail to repress under these conditions. This inability of RARß and RAR to repress transcription is due to intramolecular interactions between helix 3 and helix 12 of the hormone binding domains of these isotypes that inhibit corepressor binding while favoring coactivator binding. We report here that the converse ability of RAR to repress requires the integrity of the receptor F domain, a domain that maps C-terminal to helix 12, varies in sequence among different nuclear receptors, and is of poorly understood function. The F domain appears to help stabilize helix 12 of RAR in a more open position that enhances corepressor binding and inhibits coactivator binding in the absence of hormone. Intriguingly, the RAR F domain is isotype autonomous in its function. We speculate that the RAR F domain may dock elsewhere on the receptor surface, and this intramolecular interaction may maintain RAR helix 12 in an open, repression-competent conformation.

NURSA Molecule Pages Link:

Nuclear Receptors:   RARα  |  RARβ  |  RARγ  |  PR

Coregulators:   SRC-1  |  AIB1  |  SMRT

Ligands:   all-trans-Retinoic acid

This article has been cited by other articles:

				A. Koide, C. Zhao, M. Naganuma, J. Abrams, S. Deighton-Collins, D. F. Skafar, and S. Koide Identification of Regions within the F Domain of the Human Estrogen Receptor {alpha} that Are Important for Modulating Transactivation and Protein-Protein Interactions Mol. Endocrinol., April 1, 2007; 21(4): 829 - 842. [Abstract] [Full Text] [PDF]

				Y. A. Elhaji, I. Stoica, S. Dennis, E. O. Purisima, and M. A. Trifiro Impaired helix 12 dynamics due to proline 892 substitutions in the androgen receptor are associated with complete androgen insensitivity Hum. Mol. Genet., March 15, 2006; 15(6): 921 - 931. [Abstract] [Full Text] [PDF]

				W. Wan, B. Farboud, and M. L. Privalsky Pituitary Resistance to Thyroid Hormone Syndrome Is Associated with T3 Receptor Mutants that Selectively Impair {beta}2 Isoform Function Mol. Endocrinol., June 1, 2005; 19(6): 1529 - 1542. [Abstract] [Full Text] [PDF]