中国科学院水生生物研究所机构知识库
Advanced  
IHB OpenIR  > 水生生物分子与细胞生物学研究中心  > 期刊论文
题名: pVHL acts as a downstream target of E2F1 to suppress E2F1 activity
作者: Ji, Wei1, 2; Wang, Jing1; Zhang, Wei1; Liu, Xing1; Ouyang, Gang1; Xiao, Wuhan1
通讯作者: Xiao, WH (reprint author), Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China.
关键词: E2F1 ; interaction ; suppression ; transactivity ; von Hippel-Lindau protein (pVHL)
刊名: BIOCHEMICAL JOURNAL
发表日期: 2014
DOI: 10.1042/BJ20130793
卷: 457, 页:185-195
收录类别: SCI
文章类型: Article
部门归属: [Ji, Wei; Wang, Jing; Zhang, Wei; Liu, Xing; Ouyang, Gang; Xiao, Wuhan] Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China; [Ji, Wei] Huazhong Agr Univ, Coll Fisheries, Dept Aquat Anim Med, Wuhan 430070, Peoples R China
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
资助者: 973 Program (National Basic Research Program) [2010CB126306]; National Science Foundation of China (NSFC) [31071212, 91019008, 31031122]; National Transgene Project [2009ZX08010-021B]
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
摘要: The VHL (von Hippel-Lindau) gene is a well-defined tumour suppressor linked to hereditary cancer syndromes. Although it is well documented that pVHL (von Hippel Lindau protein) mediates HIP (hypoxia-inducible factor)-1/2 alpha degradation under conditions of normoxia, accounting for a major mechanism of pVHL in tumour suppression, it remains elusive whether other HIP-independent functions contribute to the pVHL tumour suppressive function. In the present study, we found that pVHL is a downstream target of E2F1, which harbours an E2F1-binding site in its promoter. Moreover, pVHL binds to E2F1 in vitro and in vivo, resulting in inhibition of E2F1 transcriptional activity. Mechanistic studies showed that pVHL binding enhances E2F1 deacetylation. Further immunoprecipitation assays indicated that the pVHL interaction diminishes P/CAF [p300/CREB (cAMP-response-element-binding protein)-binding protein-associated factor] and p300 association with E2F1, but enhances Sirt1 (sirtuin 1) binding to E2F1. In addition, upon DNA damage, pVHL is induced. Knockdown of pVHL sensitizes cells to DNA-damage-induced apoptosis dependent on E2F1, uncovering a role for pVHL in the response to DNA damage. The findings of the present study reveal a novel function of pVHL and demonstrate a negative-feedback loop between pVHL and E2F1, which may shed new light on the explanation of the role of pVHL in tumour suppression.
英文摘要: The VHL (von Hippel-Lindau) gene is a well-defined tumour suppressor linked to hereditary cancer syndromes. Although it is well documented that pVHL (von Hippel Lindau protein) mediates HIP (hypoxia-inducible factor)-1/2 alpha degradation under conditions of normoxia, accounting for a major mechanism of pVHL in tumour suppression, it remains elusive whether other HIP-independent functions contribute to the pVHL tumour suppressive function. In the present study, we found that pVHL is a downstream target of E2F1, which harbours an E2F1-binding site in its promoter. Moreover, pVHL binds to E2F1 in vitro and in vivo, resulting in inhibition of E2F1 transcriptional activity. Mechanistic studies showed that pVHL binding enhances E2F1 deacetylation. Further immunoprecipitation assays indicated that the pVHL interaction diminishes P/CAF [p300/CREB (cAMP-response-element-binding protein)-binding protein-associated factor] and p300 association with E2F1, but enhances Sirt1 (sirtuin 1) binding to E2F1. In addition, upon DNA damage, pVHL is induced. Knockdown of pVHL sensitizes cells to DNA-damage-induced apoptosis dependent on E2F1, uncovering a role for pVHL in the response to DNA damage. The findings of the present study reveal a novel function of pVHL and demonstrate a negative-feedback loop between pVHL and E2F1, which may shed new light on the explanation of the role of pVHL in tumour suppression.
关键词[WOS]: LINDAU TUMOR-SUPPRESSOR ; HYPOXIA-INDUCIBLE FACTOR ; DNA-DAMAGE ; RETINOBLASTOMA PROTEIN ; REPRESS TRANSCRIPTION ; HISTONE DEACETYLASE ; VASCULAR TUMORS ; CELL-DEATH ; VHL LOSS ; EXPRESSION
语种: 英语
WOS记录号: WOS:000333717900018
ISSN号: 0264-6021
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/20099
Appears in Collections:水生生物分子与细胞生物学研究中心_期刊论文

Files in This Item: Download All
File Name/ File Size Content Type Version Access License
pVHL acts as a downstream target of E2F1 to suppress E2F1 activity.pdf(1355KB)----开放获取View Download

作者单位: 1.Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China
2.Huazhong Agr Univ, Coll Fisheries, Dept Aquat Anim Med, Wuhan 430070, Peoples R China

Recommended Citation:
Ji, Wei; Wang, Jing; Zhang, Wei; Liu, Xing; Ouyang, Gang; Xiao, Wuhan.pVHL acts as a downstream target of E2F1 to suppress E2F1 activity,BIOCHEMICAL JOURNAL,2014,457():185-195
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Ji, Wei]'s Articles
[Wang, Jing]'s Articles
[Zhang, Wei]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Ji, Wei]‘s Articles
[Wang, Jing]‘s Articles
[Zhang, Wei]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit
文件名: pVHL acts as a downstream target of E2F1 to suppress E2F1 activity.pdf
格式: Adobe PDF
此文件暂不支持浏览
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  中国科学院水生生物研究所 - Feedback
Powered by CSpace