HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, S. Articles by Gardner, D. G. Search for Related Content PubMed PubMed Citation Articles by Chen, S. Articles by Gardner, D. G. Social Bookmarking                      What's this?

J Biol Chem, Vol. 275, Issue 20, 15039-15048, May 19, 2000

Coactivator-Vitamin D Receptor Interactions Mediate Inhibition of the Atrial Natriuretic Peptide Promoter^*

Songcang Chen, Junfeng Cui, Karl Nakamura, Ralff C. J. Ribeiro, Brian L. West, and David G. Gardner^§

From the Metabolic Research Unit and Department of Medicine, University of California at San Francisco, San Francisco, California 94143-0540 and the  Department of Pharmaceutical Sciences, University of Brasilia, DF 70910-900, Brazil

We have discovered a role for coactivators binding to the AF-2 surface of the vitamin D receptor (VDR) in its negative effects on gene transcription. We tested nine amino acid residues (Ser²³⁵, Ile²⁴², Lys²⁴⁶, Asp²⁵³, Ile²⁶⁰, Leu²⁶³, Leu⁴¹⁷, Leu⁴¹⁹, and Glu⁴²⁰) in human VDR which, based on homology to the human thyroid hormone receptor, would be predicted to lie in or near the coactivator-binding site. Mutation of six of these residues in VDR resulted in loss of both the activation (assessed with a transfected DR3 TK luciferase reporter) and inhibition (assessed with an hANPCAT reporter) functions of the receptor when tested in cultured neonatal rat atrial myocytes and HeLa cells. Collectively, these mutations also suppressed association of VDR with the coactivators GRIP1 and steroid receptor coactivator 1 in vitro but had little or no effect on ligand binding, heterodimerization with the retinoid X receptor, or association with a VDR-specific DNA recognition element. Co-transfection with GRIP1 or steroid receptor coactivator 1 amplified both the positive and negative responses to wild type VDR but had little or no effect on the functionally impaired mutants described above. The interaction between VDR and GRIP1 proved to be heavily dependent upon the integrity of nuclear box III in the latter protein. Mutations in this region of GRIP1 impaired its ability to associate with VDR in vitro and to amplify VDR activity in intact cells. These studies establish a role for coactivators recruited to the same receptor surface in both the activating and inhibitory activity of the liganded receptor.

---

^* This work was supported by National Institutes of Health Grant HL-35753.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^§ To whom correspondence should be addressed: Metabolic Research Unit, 1109 HSW, UCSF, San Francisco, CA 94143-0540. Tel.: 415-476-2729; Fax: 415-476-1660; E-mail: gardner@itsa.ucsf.edu.

---

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				D. G. Gardner, S. Chen, D. J. Glenn, and C. L. Grigsby Molecular Biology of the Natriuretic Peptide System: Implications for Physiology and Hypertension Hypertension, March 1, 2007; 49(3): 419 - 426. [Full Text] [PDF]

				S. Chen, X.-P. Ni, M. H. Humphreys, and D. G. Gardner 1,25 Dihydroxyvitamin D Amplifies Type A Natriuretic Peptide Receptor Expression and Activity in Target Cells J. Am. Soc. Nephrol., February 1, 2005; 16(2): 329 - 339. [Abstract] [Full Text] [PDF]

				H. J. Dubbink, R. Hersmus, C. S. Verma, H. A. G. M. van der Korput, C. A. Berrevoets, J. van Tol, A. C. J. Ziel-van der Made, A. O. Brinkmann, A. C. W. Pike, and J. Trapman Distinct Recognition Modes of FXXLF and LXXLL Motifs by the Androgen Receptor Mol. Endocrinol., September 1, 2004; 18(9): 2132 - 2150. [Abstract] [Full Text] [PDF]

				F. Liang, F. Wang, S. Zhang, and D. G. Gardner Peroxisome Proliferator Activated Receptor (PPAR){alpha} Agonists Inhibit Hypertrophy of Neonatal Rat Cardiac Myocytes Endocrinology, September 1, 2003; 144(9): 4187 - 4194. [Abstract] [Full Text] [PDF]

				P. J. Malloy, R. Xu, L. Peng, P. A. Clark, and D. Feldman A Novel Mutation in Helix 12 of the Vitamin D Receptor Impairs Coactivator Interaction and Causes Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets without Alopecia Mol. Endocrinol., November 1, 2002; 16(11): 2538 - 2546. [Abstract] [Full Text] [PDF]

				Y. Yamamoto, O. Wada, M. Suzawa, Y. Yogiashi, T. Yano, S. Kato, and J. Yanagisawa The Tamoxifen-responsive Estrogen Receptor alpha Mutant D351Y Shows Reduced Tamoxifen-dependent Interaction with Corepressor Complexes J. Biol. Chem., November 9, 2001; 276(46): 42684 - 42691. [Abstract] [Full Text] [PDF]

				L. L. Issa, G. M. Leong, J. B. Barry, R. L. Sutherland, and J. A. Eisman Glucocorticoid Receptor-Interacting Protein-1 and Receptor-Associated Coactivator-3 Differentially Interact with the Vitamin D Receptor (VDR) and Regulate VDR-Retinoid X Receptor Transcriptional Cross-Talk Endocrinology, April 1, 2001; 142(4): 1606 - 1615. [Abstract] [Full Text]

				P. Webb, P. Nguyen, C. Valentine, R. V. Weatherman, T. S. Scanlan, and P. J. Kushner An Antiestrogen-responsive Estrogen Receptor-alpha Mutant (D351Y) Shows Weak AF-2 Activity in the Presence of Tamoxifen J. Biol. Chem., November 22, 2000; 275(48): 37552 - 37558. [Abstract] [Full Text] [PDF]

				C. Zhang, T. A. Baudino, D. R. Dowd, H. Tokumaru, W. Wang, and P. N. MacDonald Ternary Complexes and Cooperative Interplay between NCoA-62/Ski-interacting Protein and Steroid Receptor Coactivators in Vitamin D Receptor-mediated Transcription J. Biol. Chem., October 26, 2001; 276(44): 40614 - 40620. [Abstract] [Full Text] [PDF]