Deleted in Breast Cancer 1, a Novel Androgen Receptor (AR) Coactivator That Promotes AR DNA-binding Activity*
- Junjiang Fu‡§,
- Jun Jiang‡,
- Jiwen Li¶,
- Shanshan Wang¶,
- Guang Shi¶,
- Qin Feng‡,
- Eileen White∥,
- Jun Qin‡** and
- Jiemin Wong¶1
- ¶The Institute of Biomedical Sciences, College of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China, the ‡Department of Molecular and Cellular Biology and the **Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, the §Xiangya School of Medicine, Central South University, Xiangya 410013, China, and the ∥Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854
- 1 To whom correspondence should be addressed. Tel.: 86-21-543-45013; Fax: 86-21-543-44922; E-mail: jmweng{at}bio.ecnu.edu.cn.
Abstract
Androgen receptor (AR) plays a critical role in development and maintenance of male reproductive functions and the etiology of prostate cancer. As a ligand-regulated transcription factor, identification and characterization of AR coregulators are essential for understanding the molecular mechanisms underlying its diverse biological functions. Here we reported the identification of a novel AR coactivator, deleted in breast cancer 1 (DBC1), through a biochemical approach. DBC1 interacts with AR in a ligand-stimulated manner and facilitates AR transcriptional activation in transfected cells as well as in Xenopus oocytes. In in vitro gel shift experiments, recombinant DBC1 drastically enhanced AR DNA-binding activity. Expression of DBC1 also enhanced the binding of AR to chromatinized template in vivo, whereas knockdown of DBC1 impaired the binding of AR to endogenous prostate-specific antigen (PSA) gene in the prostate cancer cell line LNCaP. Thus, our data identify DBC1 as a novel AR coactivator.
Footnotes
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↵2 The abbreviations used are: AR, androgen receptor; NR, nuclear receptor; LBD, ligand-binding domain; DBC1, deleted in breast cancer 1; aa, amino acid(s); GST, glutathione S-transferase; HA, hemagglutinin; DSP, dithiobis(succinimidyl propionate); MMTV, murine mammary tumor virus; siRNA, small interference RNA; RT, reverse transcription; ChIP, chromatin immunoprecipitation; IP, immunoprecipitation; LTR, long terminal repeat; ERα, estrogen receptor α.
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↵* This work was supported by the Research Platform of Cell Signaling Networks from the Science and Technology Commission of Shanghai Municipality (Grant 06DZ22923) and the Educational Department of China (to J. W.) and by Grant 30371493 from Natural Science Foundation of China (to J. F.). 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.
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- Received December 1, 2008.
- Revision received December 29, 2008.
- The American Society for Biochemistry and Molecular Biology, Inc.
