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IR@PKUHSC  > 北京大学临床肿瘤学院  > 遗传学研究室  > 期刊论文
学科主题: 临床医学
题名:
Human papillomavirus 16 E6 oncoprotein interferences with insulin signaling pathway by binding to tuberin
作者: 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
发表日期: 2004-08-20
DOI: 10.1074/jbc.M403385200
卷: 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
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53539
Appears in Collections:北京大学临床肿瘤学院_遗传学研究室_期刊论文

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作者单位: Peking Univ, Sch Oncol, Beijing Inst Canc Res, Dept Genet, Beijing 100034, Peoples R China

Recommended Citation:
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.
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