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) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions 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. 274, Issue 16, 11260-11266, April 16, 1999

Vitamin D-dependent Suppression of Human Atrial Natriuretic Peptide Gene Promoter Activity Requires Heterodimer Assembly

Songcang Chen, Claudia H. R. M. Costa, Karl Nakamura, Ralff C. J. Ribeiro, and David G. Gardner

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

Crystallographic structures of the ligand-binding domains for the retinoid X (RXR) and estrogen receptors have identified conserved surface residues that participate in dimer formation. Homologous regions have been identified in the human vitamin D receptor (hVDR). Mutating Lys-386 to Ala (K386A) in hVDR significantly reduced binding to glutathione S-transferase-RXR in solution, whereas binding of an I384R/Q385R VDR mutant was almost undetectable. The K386A mutant formed heterodimers with RXR on DR-3 (a direct repeat of AGGTCA spaced by three nucleotides), whereas the I384R/Q385R mutant completely eliminated heterodimer formation. Wild type hVDR effected a 3-fold induction of DR-3-dependent thymidine kinase-luciferase activity in cultured neonatal rat atrial myocytes, an effect that was increased to 8-9-fold by cotransfected hRXR. Induction by K386A, in the presence or absence of RXR, was only slightly lower than that seen with wild type VDR. On the other hand, I384R/Q385R alone displayed no stimulatory activity and less than 2-fold induction in the presence of hRXR. Qualitatively similar findings were observed with the negative regulation of the human atrial natriuretic peptide gene promoter by these mutants. Collectively, these studies identify specific amino acids in hVDR that play a critical role in heterodimer formation and subsequent modulation of gene transcription.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				S. Chen, D. J. Glenn, W. Ni, C. L. Grigsby, K. Olsen, M. Nishimoto, C. S. Law, and D. G. Gardner Expression of the Vitamin D Receptor Is Increased in the Hypertrophic Heart Hypertension, December 1, 2008; 52(6): 1106 - 1112. [Abstract] [Full Text] [PDF]

				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]

				J. Eeckhoute, B. Oxombre, P. Formstecher, P. Lefebvre, and B. Laine Critical role of charged residues in helix 7 of the ligand binding domain in Hepatocyte Nuclear Factor 4{alpha} dimerisation and transcriptional activity Nucleic Acids Res., November 15, 2003; 31(22): 6640 - 6650. [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. Aarnisalo, C.-H. Kim, J. W. Lee, and T. Perlmann Defining Requirements for Heterodimerization between the Retinoid X Receptor and the Orphan Nuclear Receptor Nurr1 J. Biol. Chem., September 13, 2002; 277(38): 35118 - 35123. [Abstract] [Full Text] [PDF]

				S. Chen, J. Cui, K. Nakamura, R. C. J. Ribeiro, B. L. West, and D. G. Gardner Coactivator-Vitamin D Receptor Interactions Mediate Inhibition of the Atrial Natriuretic Peptide Promoter J. Biol. Chem., May 12, 2000; 275(20): 15039 - 15048. [Abstract] [Full Text] [PDF]

				K. Prufer, A. Racz, G. C. Lin, and J. Barsony Dimerization with Retinoid X Receptors Promotes Nuclear Localization and Subnuclear Targeting of Vitamin D Receptors J. Biol. Chem., December 22, 2000; 275(52): 41114 - 41123. [Abstract] [Full Text] [PDF]

				R. C. J. Ribeiro, W. Feng, R. L. Wagner, C. H. R. M. Costa, A. C. Pereira, J. W. Apriletti, R. J. Fletterick, and J. D. Baxter Definition of the Surface in the Thyroid Hormone Receptor Ligand Binding Domain for Association as Homodimers and Heterodimers with Retinoid X Receptor J. Biol. Chem., April 27, 2001; 276(18): 14987 - 14995. [Abstract] [Full Text] [PDF]