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J. Biol. Chem., Vol. 280, Issue 20, 20000-20009, May 20, 2005

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NRIP, a Novel Nuclear Receptor Interaction Protein, Enhances the Transcriptional Activity of Nuclear Receptors^*

Tzung-Chieh Tsai, Yung-Lu Lee, Wei-Chih Hsiao, Yeou-Ping Tsao¶, and Show-Li Chen||

From the Graduate Institute of Life Sciences, Department of Microbiology and Immunology, National Defense Medical Center, Taipei 114 and the ^¶Department of Ophthalmology, Mackay Memorial Hospital, Taipei 104, Taiwan

Transcriptional regulation by members of the nuclear hormone receptor superfamily is a modular process requiring the mediation of distinct subclasses of coregulators. In this study, we isolated a novel WD40 repeat-containing gene, human nuclear receptor interaction protein (NRIP). We found NRIP interacts with either androgen or glucocorticoid receptors from in vitro and in vivo pulldown assays. Subsequently, transient transfection and luciferase activity assays suggested that NRIP was a ligand-dependent coactivator of steroid receptors (androgen and glucocorticoid) in distinct promoters. To further clarify the function of NRIP, we found an RNA interference-3-targeted NRIP gene sequence (5'-GATGATACAGCACGAGAAC-3') that could efficiently and specifically knock down endogenous and exogenous NRIP gene expression and that significantly diminished cell proliferation in prostate (LNCaP) and cervical (C33A) cells. Therefore, NRIP may play a role in enhancing the transcriptional activity of nuclear receptors and may be a critical target for developing therapeutic agents against nuclear receptor-mediated progression of prostate and cervical cancers.

Received for publication, October 27, 2004 , and in revised form, March 7, 2005.

^* This work was supported by National Science Council Grants NSC 92-2320-B-016-063 and NSC 92-3112-B-016-003-M51 and National Health Research Institute Grant NHRI-EX92-9013BL. 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.

The nucleotide sequence(s) reported in this paper has been submitted to the DDBJ/GenBank^TM/EBI Data Bank with accession number(s) AY766164 and AAX09330

^|| To whom correspondence should be addressed. Tel.: 886-2-87924895; Fax: 886-2-87924885; E-mail: sltsao{at}mail.ndmctsgh.edu.tw.

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