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 Dwivedi, P. P. Articles by May, B. K. Search for Related Content PubMed PubMed Citation Articles by Dwivedi, P. P. Articles by May, B. K. Social Bookmarking                      What's this?

J Biol Chem, Vol. 275, Issue 1, 47-55, January 7, 2000

Regulation of Rat Cytochrome P450C24 (CYP24) Gene Expression
EVIDENCE FOR FUNCTIONAL COOPERATION OF Ras-ACTIVATED Ets TRANSCRIPTION FACTORS WITH THE VITAMIN D RECEPTOR IN 1,25-DIHYDROXYVITAMIN D₃-MEDIATED INDUCTION^*

Prem P. Dwivedi, John L. Omdahl^§¶, Ismail Kola, David A. Hume^**, and Brian K. May

From the  Department of Biochemistry, University of Adelaide, Adelaide, South Australia 5005, Australia, the ^§ Department of Biochemistry and Molecular Biology, University of New Mexico, Albuquerque, New Mexico 87131, the  Molecular Genetics and Development Group, Institute of Reproduction and Development, Monash University, Melbourne, Victoria 3168, Australia, and the ^** Center for Molecular and Cellular Biology, University of Queensland, St. Lucia, Queensland 4072, Australia

Transcription of the rat CYP24 gene is induced by 1,25-dihydroxyvitamin D₃ (1,25-(OH)₂D₃) through two vitamin D response elements (VDREs). A functional Ras-dependent Ets-binding site (EBS) was located downstream from the proximal VDRE and was critical to 1,25(OH)₂D₃-mediated induction. Cotransfection of Ets-1 and Ets-2 stimulated induction, which was lost when the EBS was mutated. Multiple nuclear-protein complexes from COS-1 cells bound to the EBS in which three complexes were immunologically related to Ets-1. Transcriptional synergy was observed between the proximal VDRE and adjacent EBS as was the attendant formation of a ternary complex between vitamin D receptor- retinoid X receptor (VDR·RXR) and Ets-1. In the absence of 1,25-(OH)₂D₃ or in the presence of an inactive proximal VDRE, the EBS failed to respond to exogenous Ets-1. However, Ets-1 increased basal expression when cotransfected with a mutant VDR. The inductive action of 1,25-(OH)₂D₃ was substantially increased by Ras, which was ablated by mutagenesis of the EBS or by expression of a mutated Ets-1 protein (T38A). EBS contribution to hormone induction was prevented by manumycin A, an inhibitor of Ras farnesylation. A fundamental role was established for transcriptional cooperation between Ras-activated Ets proteins and the VDR·RXR complex in mediating 1,25-(OH)₂D₃ action on the CYP24 promoter.

---

^* This work was supported by research funds from the Australian Research Council and University of New Mexico Medical Trust Fund.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: Dept. of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM 87131-5221. Tel.: 505-272-5791; Fax: 505-272-6587; E-mail: jomdahl@salud.unm.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:

				S. CHRISTAKOS, P. DHAWAN, B. BENN, A. PORTA, M. HEDIGER, G. T. OH, E.-B. JEUNG, Y. ZHONG, D. AJIBADE, K. DHAWAN, et al. Vitamin D: Molecular Mechanism of Action Ann. N.Y. Acad. Sci., November 1, 2007; 1116(1): 340 - 348. [Abstract] [Full Text] [PDF]

				P. P Dwivedi, P. H Anderson, J. L Omdahl, H L. Grimes, H. A Morris, and B. K May Identification of growth factor independent-1 (GFI1) as a repressor of 25-hydroxyvitamin D 1-alpha hydroxylase (CYP27B1) gene expression in human prostate cancer cells Endocr. Relat. Cancer, June 1, 2005; 12(2): 351 - 365. [Abstract] [Full Text] [PDF]

				L. Sinkkonen, M. Malinen, K. Saavalainen, S. Vaisanen, and C. Carlberg Regulation of the human cyclin C gene via multiple vitamin D3-responsive regions in its promoter Nucleic Acids Res., April 29, 2005; 33(8): 2440 - 2451. [Abstract] [Full Text] [PDF]

				P. Dhawan, X. Peng, A. L. M. Sutton, P. N. MacDonald, C. M. Croniger, C. Trautwein, M. Centrella, T. L. McCarthy, and S. Christakos Functional Cooperation between CCAAT/Enhancer-Binding Proteins and the Vitamin D Receptor in Regulation of 25-Hydroxyvitamin D3 24-Hydroxylase Mol. Cell. Biol., January 1, 2005; 25(1): 472 - 487. [Abstract] [Full Text] [PDF]

				F. Barletta, P. Dhawan, and S. Christakos Integration of hormone signaling in the regulation of human 25(OH)D3 24-hydroxylase transcription Am J Physiol Endocrinol Metab, April 1, 2004; 286(4): E598 - E608. [Abstract] [Full Text] [PDF]

				E. Aklillu, J. A. Carrillo, E. Makonnen, K. Hellman, M. Pitarque, L. Bertilsson, and M. Ingelman-Sundberg Genetic Polymorphism of CYP1A2 in Ethiopians Affecting Induction and Expression: Characterization of Novel Haplotypes with Single-Nucleotide Polymorphisms in Intron 1 Mol. Pharmacol., September 1, 2003; 64(3): 659 - 669. [Abstract] [Full Text] [PDF]

				P. P. Dwivedi, C. S. T. Hii, A. Ferrante, J. Tan, C. J. Der, J. L. Omdahl, H. A. Morris, and B. K. May Role of MAP Kinases in the 1,25-Dihydroxyvitamin D3-induced Transactivation of the Rat Cytochrome P450C24 (CYP24) Promoter. SPECIFIC FUNCTIONS FOR ERK1/ERK2 AND ERK5 J. Biol. Chem., August 9, 2002; 277(33): 29643 - 29653. [Abstract] [Full Text] [PDF]