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

J. Biol. Chem., Vol. 280, Issue 10, 8819-8830, March 11, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/10/8819    most recent M413184200v2 M413184200v1 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 Lee, J. E. Articles by Safe, S. Search for Related Content PubMed PubMed Citation Articles by Lee, J. E. Articles by Safe, S. Social Bookmarking                      What's this?

DRIP150 Coactivation of Estrogen Receptor in ZR-75 Breast Cancer Cells Is Independent of LXXLL Motifs^*

Jeongeun Eun Lee, Kyounghyun Kim, James C. Sacchettini¶, Clare V. Smith, and Stephen Safe¶||

From the Department of Veterinary Physiology and Pharmacology, the Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843-4466, and ^¶Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, Texas 77030-3303

Vitamin D receptor-interacting protein 150 (DRIP150) has been identified as part of mediator-like complexes that enhance transcriptional activation of the estrogen receptor (ER) and other nuclear receptors (NRs). DRIP150 coactivates ligand-dependent ER-mediated transactivation in ZR-75 and MDA-MB-231 breast cancer cells transfected with a (luciferase) reporter construct (pERE₃) regulated by three tandem estrogen-responsive elements. Coactivation of ER by DRIP150 in ZR-75 cells was activation function 2-dependent and required an intact helix 12 that typically interacts with LXXLL motifs (NR box) in p160 steroid receptor coactivators. DRIP150 contains C- and N-terminal NR boxes (amino acids 1182–1186 and 69–73, respectively), and deletion analysis of DRIP150 showed that regions containing these sequences were not necessary for coactivation of ER. Analysis of multiple DRIP150 deletion mutants identified a 23-amino-acid sequence (789–811) required for coactivation activity. Analysis of the protein crystal structure data base identified two regions at amino acids 789–794 and 795–804, which resembled -helical motifs in Lanuginosa lipase/histamine N-methyltransferase and hepatocyte nuclear factor 1, respectively. By using a squelching assay and specific amino acid point mutations within each -helix, the NIFSEVRVYN (795–804) region was identified as the critical sequence required for the activity of DRIP150. These results demonstrate that coactivation of ER by DRIP150 in ZR-75 cells is NR box-independent and requires a novel sequence with putative -helical structure.

Received for publication, November 22, 2004

^* This work was supported by National Institutes of Health Grants ES09106 and CA104116 and the Texas Agricultural Experiment Station. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| Sid Kyle Professor of Toxicology. To whom correspondence should be addressed: Dept. of Veterinary Physiology and Pharmacology, Texas A&M University, 4466 TAMU, Veterinary Research Bldg. 409, College Station, TX 77843-4466. Tel.: 979-845-5988; Fax: 979-862-4929; E-mail: ssafe{at}cvm.tamu.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Nath-Sain and P. A. Marignani LKB1 Catalytic Activity Contributes to Estrogen Receptor {alpha} Signaling Mol. Biol. Cell, June 1, 2009; 20(11): 2785 - 2795. [Abstract] [Full Text] [PDF]

				N. Ding, C. Tomomori-Sato, S. Sato, R. C. Conaway, J. W. Conaway, and T. G. Boyer MED19 and MED26 Are Synergistic Functional Targets of the RE1 Silencing Transcription Factor in Epigenetic Silencing of Neuronal Gene Expression J. Biol. Chem., January 30, 2009; 284(5): 2648 - 2656. [Abstract] [Full Text] [PDF]

				W. Chen and R. G. Roeder The Mediator subunit MED1/TRAP220 is required for optimal glucocorticoid receptor-mediated transcription activation Nucleic Acids Res., September 25, 2007; 35(18): 6161 - 6169. [Abstract] [Full Text] [PDF]

				S. M Dougherty, W. Mazhawidza, A. R Bohn, K. A Robinson, K. A Mattingly, K. A Blankenship, M. O Huff, W. G McGregor, and C. M Klinge Gender difference in the activity but not expression of estrogen receptors {alpha} and {beta} in human lung adenocarcinoma cells. Endocr. Relat. Cancer, March 1, 2006; 13(1): 113 - 134. [Abstract] [Full Text] [PDF]