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学科主题临床医学
Human papillomavirus 16 E6 oncoprotein interferences with insulin signaling pathway by binding to tuberin
Lu, ZM; Hu, XH; Li, Y; Zheng, L; Zhou, Y; Jiang, HD; Ning, T; Basang, Z; Zhang, CF; Ke, Y
刊名JOURNAL OF BIOLOGICAL CHEMISTRY
2004-08-20
DOI10.1074/jbc.M403385200
279期:34页:35664-35670
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology
研究领域[WOS]Biochemistry & Molecular Biology
关键词[WOS]HUMAN-PAPILLOMAVIRUS TYPE-16 ; TUMOR-SUPPRESSOR PROTEINS ; GENE-PRODUCTS ; CELL-GROWTH ; SCLEROSIS GENE ; MEDIATED DEGRADATION ; HUMAN KERATINOCYTES ; DIRECT TARGET ; TSC2 ; RHEB
英文摘要

Tuberous sclerosis complex (TSC) is a genetic disorder caused by mutations in either TSC1 or TSC2 tumor suppressor gene. TSC1 and TSC2 products, Harmatin and Tuberin, form the functional complex to serve as the negative regulator for insulin-induced phosphorylation of S6 kinase and elF4E-binding protein 1. High-risk human papillomavirus (HPV) infection is the necessary cause for cervical cancer. E6 oncoprotein encoded by HPV plays a pivotal role in carcinogenesis by interference with the host intracellular protein functions. In this study, we show that HPV16 E6 interacts with tumor suppressor gene TSC2 product, Tuberin, and results in the phosphorylation of S6 kinase and S6 even in the absence of insulin. The overexpression of Tuberin overcomes the effect of E6 on S6 kinase phosphorylation. Binding with HPV16 E6 causes the proteasome-mediated degradation of Tuberin. A DILG motif and an ELVG motif located in the carboxyl-terminal of Tuberin are required for E6 binding. In addition, the Tuberin interaction region in E6 has been mapped in the amino-terminal portion of HPV16 E6, which is different from the binding domain with p53. These results provide a possible link between E6-induced oncogenesis and the insulin-stimulated cell proliferation signaling pathway.

语种英语
WOS记录号WOS:000223303400063
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被引频次:70[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/53539
专题北京大学临床肿瘤学院_遗传学研究室
作者单位Peking Univ, Sch Oncol, Beijing Inst Canc Res, Dept Genet, Beijing 100034, Peoples R China
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Lu, ZM,Hu, XH,Li, Y,et al. Human papillomavirus 16 E6 oncoprotein interferences with insulin signaling pathway by binding to tuberin[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2004,279(34):35664-35670.
APA Lu, ZM.,Hu, XH.,Li, Y.,Zheng, L.,Zhou, Y.,...&Ke, Y.(2004).Human papillomavirus 16 E6 oncoprotein interferences with insulin signaling pathway by binding to tuberin.JOURNAL OF BIOLOGICAL CHEMISTRY,279(34),35664-35670.
MLA Lu, ZM,et al."Human papillomavirus 16 E6 oncoprotein interferences with insulin signaling pathway by binding to tuberin".JOURNAL OF BIOLOGICAL CHEMISTRY 279.34(2004):35664-35670.
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