NRIP, a novel nuclear receptor interaction protein, enhances the transcriptional activity of nuclear receptors
NRIP, a novel nuclear receptor interaction protein, enhances the transcriptional activity of nuclear receptors
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DOI：
10.1074/jbc.m412169200
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发表时间：
2005-05-20
影响因子：
4.8
通讯作者：
Chen, SL
中科院分区：
文献类型：
--
作者：
Tsai, TC;Lee, YL;Chen, SL
核激素受体超家族成员的转录调控是一个模块化的过程，需要不同的辅调节子亚类的介导。在本研究中，我们分离了一个新的含WD 40重复序列的基因，人核受体相互作用蛋白（NRIP）。我们发现NRIP与雄激素或糖皮质激素受体相互作用，在体外和体内下拉测定。随后，瞬时转染和荧光素酶活性测定表明，NRIP是不同启动子中类固醇受体（雄激素和糖皮质激素）的配体依赖性共激活剂。为了进一步阐明NRIP的功能，我们发现了RNA干扰-3-靶向的NRIP基因序列（5 '-GATGATACAGCACGAGAAC-3'），其可以有效且特异性地敲低内源性和外源性NRIP基因表达，并且显著减少前列腺（LNCaP）和宫颈（C33 A）细胞中的细胞增殖。因此，NRIP可能在增强核受体的转录活性中发挥作用，并且可能是开发针对核受体介导的前列腺癌和宫颈癌进展的治疗剂的关键靶标。
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.