Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Amino Acid Sequence
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Animals
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Base Sequence
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Cell Line
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Cell Line, Tumor
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Cell Proliferation
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DNA / genetics
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Female
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Humans
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In Vitro Techniques
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Male
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Mice
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Molecular Sequence Data
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Neoplasms, Hormone-Dependent / genetics
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Neoplasms, Hormone-Dependent / metabolism
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Neoplasms, Hormone-Dependent / pathology
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Nuclear Proteins / antagonists & inhibitors
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Pregnancy
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Prostatic Neoplasms / genetics
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology
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RNA Interference
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Androgen / genetics
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Receptors, Androgen / metabolism
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Receptors, Cytoplasmic and Nuclear / genetics*
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Receptors, Glucocorticoid / genetics
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Receptors, Glucocorticoid / metabolism
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Sequence Homology, Amino Acid
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Tissue Distribution
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Transcription, Genetic
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Two-Hybrid System Techniques
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Uterine Cervical Neoplasms / genetics
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Uterine Cervical Neoplasms / metabolism
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Uterine Cervical Neoplasms / pathology
Substances
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Adaptor Proteins, Signal Transducing
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DCAF6 protein, human
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Nuclear Proteins
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RNA, Messenger
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Receptors, Androgen
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Receptors, Cytoplasmic and Nuclear
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Receptors, Glucocorticoid
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DNA
Associated data
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GENBANK/AAX09330
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GENBANK/AY766164