SOX2 as a New Regulator of HPV16 Transcription.
SOX2 as a New Regulator of HPV16 Transcription.
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DOI：
10.3390/v9070175
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发表时间：
2017-07-05
期刊：
影响因子：
--
通讯作者：
Lizano M
中科院分区：
文献类型：
--
作者：
Martínez-Ramírez I;Del-Castillo-Falconi V;Mitre-Aguilar IB;Amador-Molina A;Carrillo-García A;Langley E;Zentella-Dehesa A;Soto-Reyes E;García-Carrancá A;Herrera LA;Lizano M
高危型人乳头瘤病毒（HPV）的持续感染是宫颈癌发展的主要危险因素。HPV 16是与鳞状细胞癌（SCC）相关的最常见类型，其次是HPV 18。HPV基因组中的长控制区（LCR）包含复制起点和控制病毒转录的细胞转录因子（TF）识别的序列。受LCR调节的E6和E7病毒癌基因的表达改变，导致细胞途径的改变，如增殖，导致恶性转化。本研究的目的是确定特定的TF，可能有助于调节高危型HPV的转录活性，与细胞组织学起源。我们鉴定了HPV 16-LCR中存在的性别决定区Y（SRY）-框2（SOX 2）反应元件。通过体内和体外测定证明了SOX 2与LCR的结合。该TF的过表达抑制了HPV 16-LCR的转录活性，如通过报告质粒测定和内源性HPV癌基因的下调所示。定点突变显示，三个推定的SOX 2结合位点参与LCR活性的抑制。我们认为SOX 2作为HPV 16-LCR的转录抑制因子，在SCC背景下降低E6和E7癌基因的表达。
Persistent infections with high-risk human papillomavirus (HPV) constitute the main risk factor for cervical cancer development. HPV16 is the most frequent type associated to squamous cell carcinomas (SCC), followed by HPV18. The long control region (LCR) in the HPV genome contains the replication origin and sequences recognized by cellular transcription factors (TFs) controlling viral transcription. Altered expression of E6 and E7 viral oncogenes, modulated by the LCR, causes modifications in cellular pathways such as proliferation, leading to malignant transformation. The aim of this study was to identify specific TFs that could contribute to the modulation of high-risk HPV transcriptional activity, related to the cellular histological origin. We identified sex determining region Y (SRY)-box 2 (SOX2) response elements present in HPV16-LCR. SOX2 binding to the LCR was demonstrated by in vivo and in vitro assays. The overexpression of this TF repressed HPV16-LCR transcriptional activity, as shown through reporter plasmid assays and by the down-regulation of endogenous HPV oncogenes. Site-directed mutagenesis revealed that three putative SOX2 binding sites are involved in the repression of the LCR activity. We propose that SOX2 acts as a transcriptional repressor of HPV16-LCR, decreasing the expression of E6 and E7 oncogenes in a SCC context.
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影响因子：
5.4
作者：
CHONG, T;APT, D;BERNARD, HU
通讯作者：
BERNARD, HU
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影响因子：
64.8
作者：
Boumahdi, Soufiane;Driessens, Gregory;Blanpain, Cedric
通讯作者：
Blanpain, Cedric
影响因子：
14.9
作者：
CHAN, WK;CHONG, T;KLOCK, G
通讯作者：
KLOCK, G
影响因子：
30.8
作者：
Bass, Adam J.;Watanabe, Hideo;Mermel, Craig H.;Yu, Soyoung;Perner, Sven;Verhaak, Roel G.;Kim, So Young;Wardwell, Leslie;Tamayo, Pablo;Gat-Viks, Irit;Ramos, Alex H.;Woo, Michele S.;Weir, Barbara A.;Getz, Gad;Beroukhim, Rameen;O'Kelly, Michael;Dutt, Amit;Rozenblatt-Rosen, Orit;Dziunycz, Piotr;Komisarof, Justin;Chirieac, Lucian R.;LaFargue, Christopher J.;Scheble, Veit;Wilbertz, Theresia;Ma, Changqing;Rao, Shilpa;Nakagawa, Hiroshi;Stairs, Douglas B.;Lin, Lin;Giordano, Thomas J.;Wagner, Patrick;Minna, John D.;Gazdar, Adi F.;Zhu, Chang Qi;Brose, Marcia S.;Cecconello, Ivan;Ribeiro, Ulysses, Jr.;Marie, Suely K.;Dahl, Olav;Shivdasani, Ramesh A.;Tsao, Ming-Sound;Rubin, Mark A.;Wong, Kwok K.;Regev, Aviv;Hahn, William C.;Beer, David G.;Rustgi, Anil K.;Meyerson, Matthew
通讯作者：
Meyerson, Matthew