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 HIF (hypoxia-inducible factor)-1/2α degradation under conditions of normoxia, accounting for a major mechanism of pVHL in tumour suppression, it remains elusive whether other HIF-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.
Skip Nav Destination
Article navigation
January 2014
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
December 10 2013
pVHL acts as a downstream target of E2F1 to suppress E2F1 activity
Wei Ji;
Wei Ji
*The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, People's Republic of China
†Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan 430070, People's Republic of China
Search for other works by this author on:
Jing Wang;
Jing Wang
*The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, People's Republic of China
Search for other works by this author on:
Wei Zhang;
Wei Zhang
*The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, People's Republic of China
Search for other works by this author on:
Xing Liu;
Xing Liu
*The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, People's Republic of China
Search for other works by this author on:
Gang Ouyang;
Gang Ouyang
*The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, People's Republic of China
Search for other works by this author on:
Wuhan Xiao
Wuhan Xiao
1
*The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, People's Republic of China
1To whom correspondence should be addressed (email w-xiao@ihb.ac.cn).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
June 14 2013
Revision Received:
October 11 2013
Accepted:
October 11 2013
Accepted Manuscript online:
October 11 2013
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem J (2014) 457 (1): 185–195.
Article history
Received:
June 14 2013
Revision Received:
October 11 2013
Accepted:
October 11 2013
Accepted Manuscript online:
October 11 2013
Citation
Wei Ji, Jing Wang, Wei Zhang, Xing Liu, Gang Ouyang, Wuhan Xiao; pVHL acts as a downstream target of E2F1 to suppress E2F1 activity. Biochem J 1 January 2014; 457 (1): 185–195. doi: https://doi.org/10.1042/BJ20130793
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.