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ABSTRACT: We previously identified a gene, nuclear receptor-interaction protein (NRIP), which functions as a transcription cofactor in glucocorticoid receptor (GR) and human papillomavirus E2 (HPV E2)-driven gene expression. Here, we comprehensively evaluated the role of NRIP in HPV-16 gene expression. NRIP acts as a transcription cofactor to enhance GR-regulated HPV-16 gene expression in the presence of hormone. NRIP also can form complex with E2 that caused NRIP-induced HPV gene expression via E2-binding sites in a hormone-independent manner. Furthermore, NRIP can associate with GR and E2 to form tri-protein complex to activate HPV gene expression via GRE, not the E2-binding site, in a hormone-dependent manner. These results indicate that NRIP and GR are viral E2-binding proteins and that NRIP regulates HPV gene expression via GRE and/or E2 binding site in the HPV promoter in a hormone-dependent or independent manner, respectively.
Virology 12/2011; 423(1):38-48. · 3.35 Impact Factor
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ABSTRACT: Oral carcinoma is a serious public health problem and the leading cause of head and neck cancer mortality worldwide. Moreover, oral cancer patients often present symptoms at a late stage and show a high recurrence rate after treatment. Therefore, there is an urgent need to identify novel biomarkers for early diagnosis or clinical oral cancer therapy. In this study, we employed a subset of lentiviral short hairpin RNAs targeted against various kinases and phosphatases, designed by The RNAi Consortium, to screen systemically and in a high-throughput manner for potential growth regulators of oral cancer cells. The screen revealed a total of 50 candidate genes, for which more than 90% of growth inhibition in human oral squamous cancer HSC-3 cells was obtained. Furthermore, bioinformatic analysis of these candidate genes identified transforming growth factor-β receptor type II- and fms-related tyrosine kinase 3-related molecular pathways that are involved in NF-κB-mediated growth of HSC-3 cells. These candidate genes may be potential biomarkers for early diagnosis of oral cancer. In addition, these candidate genes represent potential targets for anticancer drug design helping to develop a personalized treatment to combat oral cancer.
International Journal of Oncology 06/2011; 39(5):1221-31. · 2.40 Impact Factor
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ABSTRACT: Breast cancer amplified sequence 2 (BCAS2) was reported previously as a transcriptional coactivator of estrogen receptor. Here, we report that BCAS2 directly interacts with p53 to reduce p53 transcriptional activity by mildly but consistently decreasing p53 protein in the absence of DNA damage. However, in the presence of DNA damage, BCAS2 prominently reduces p53 protein and provides protection against chemotherapeutic agent such as doxorubicin. Deprivation of BCAS2 induces apoptosis in p53 wild-type cells but causes G(2)-M arrest in p53-null or p53 mutant cells. There are at least two apoptosis mechanisms induced by silencing BCAS2 in wild-type p53-containing cells. Firstly, it increases p53 retention in nucleus that triggers the expression of apoptosis-related genes. Secondly, it increases p53 transcriptional activity by raising p53 phosphorylation at Ser(46) and decreases p53 protein degradation by reducing p53 phosphorylation at Ser(315). We show for the first time that BCAS2, a small nuclear protein (26 kDa), is a novel negative regulator of p53 and hence a potential molecular target for cancer therapy.
Cancer Research 11/2009; 69(23):8877-85. · 7.86 Impact Factor
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ABSTRACT: HER2/neu oncogene-mediated malignancy is clearly associated with various human cancers. Therefore, HER2/neu targeting is an effective approach to cancer therapy. We have previously demonstrated that Epstein-Barr virus nuclear antigen-1 (EBNA1) can suppress HER2/neu oncogene expression, although EBNA1 itself has oncogenic potential. Here, we found that the N-terminal domain of EBNA1 alone, named EBNA1-NT, which contains the N-terminal region of amino acid residues 1-86 of EBNA1, is required and sufficient to suppress HER2/neu oncogene expression at the transcriptional level. Furthermore, in EBNA1-NT-transfected HER2/neu-overexpressing cells, we found EBNA1-NT could down-regulate the endogenous production of p185(HER2/neu), lower transformation ability, sensitize paclitaxel-induced apoptosis and decrease tumorigenic potential. These data suggest that EBNA1-NT may act as a repressor of the HER2/neu oncogene.
Cancer letters 10/2008; 273(2):273-80. · 4.86 Impact Factor
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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.
Journal of Biological Chemistry 06/2005; 280(20):20000-9. · 4.77 Impact Factor
