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学科主题: 临床医学
题名:
E3 ubiquitin ligase E6AP-mediated TSC2 turnover in the presence and absence of HPV16 E6
作者: Zheng, Li1; Ding, Huirong1; Lu, Zheming1; Li, Yong1; Pan, Yaqi1; Ning, Tao1; Ke, Yang1,2,3
刊名: GENES TO CELLS
发表日期: 2008-03-01
DOI: 10.1111/j.1365-2443.2008.01162.x
卷: 13, 期:3, 页:285-294
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology ; Genetics & Heredity
研究领域[WOS]: Cell Biology ; Genetics & Heredity
关键词[WOS]: HUMAN-PAPILLOMAVIRUS TYPE-16 ; SCLEROSIS GENE-2 PRODUCT ; TUBEROUS-SCLEROSIS ; CELL-GROWTH ; MEDIATED DEGRADATION ; SIGNALING NETWORK ; TYROSINE KINASE ; PROTEIN LIGASE ; P53 ; RHEB
英文摘要:

We previously found that HPV16 E6 causes the degradation of the tumor suppressor protein TSC2, resulting in the phosphorylation of S6 kinase and S6 even in the absence of insulin. In the present study, we investigated the role of E6-associated protein (E6AP) in HPV16 E6-induced TSC2 degradation. Our results demonstrated that TSC2 was targeted for degradation in the presence or absence of HPV16 E6. Over-expression of E6AP enhanced the degradation of TSC2 by HPV16 E6, while expression of a dominant negative E6AP (C833A) inhibited the E6-induced degradation. Additionally, by using shRNAs to block E6AP expression in HPV16 positive and negative cells, we found a significantly prolonged TSC2 half-life. An in vivo ubiquitination assay was done to reveal that E6AP promoted the ubiquitination of TSC2 independent of HPV16 E6. We further found that TSC2 bound E6AP in the presence as well as in the absence of HPV16 E6. The binding regions on E6AP and TSC2 have been identified as amino acid (aa) 260-316, aa 428-500 and aa 1-175, aa 1251-1807, respectively. Taken together, degradation of TSC2 is mediated by E6AP ubiquitin ligase.

语种: 英语
WOS记录号: WOS:000253478100006
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50180
Appears in Collections:北京大学临床肿瘤学院_期刊论文

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作者单位: 1.Peking Univ, Sch Oncol, Beijing Inst Canc Res, Beijing 100036, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Canc Res Ctr, Beijing 100083, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Dept Cell Biol, Beijing 100083, Peoples R China

Recommended Citation:
Zheng, Li,Ding, Huirong,Lu, Zheming,et al. E3 ubiquitin ligase E6AP-mediated TSC2 turnover in the presence and absence of HPV16 E6[J]. GENES TO CELLS,2008,13(3):285-294.
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