Journal
CELLULAR SIGNALLING
Volume 23, Issue 1, Pages 193-200Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2010.09.003
Keywords
E2F1; p53; MDM2-p53 feedback loop; MDM2; Apoptosis
Categories
Funding
- National Natural Science Foundation of China [30728003, 30871290, 31030046]
- Ministry of Science and Technology of China [2010CB912804]
- Ph.D. Programs Foundation of Ministry of Education of China [200803580063]
- Natural Science Foundation of Anhui province [070413082]
Ask authors/readers for more resources
MDM2 expression is down-regulated upon E2F1 over-expression, but the mechanism is not well defined. In the current study, we found that E2F1 inhibits MDM2 expression by suppressing its promoter activity. Although E2F1 binds to the MDM2 promoter, the inhibitory effect of E2F1 on the MDM2 promoter does not require the direct binding. We demonstrate that E2F1 inhibits MDM2 promoter activity in a p53-dependent manner. Knockdown of p53 in U2OS cells impairs the inhibitory effect of E2F1 on the MDM2 promoter. Consistent with this observation, E2F1 does not inhibit MDM2 promoter activity in p53-deficient H1299 cells. and the inhibition is restored when p53 is expressed exogenously. Both E2F1 and p53 are up-regulated after DNA damage stimulation. We show that such stimulation induces E2F1 to inhibit MDM2 promoter activity and promote p53 accumulation. Furthermore, inhibition of MDM2 by E2F1 promotes E2F1 induced apoptosis. These data suggest that E2F1 regulates the MDM2-p53 pathway by inhibiting p53 induced up-regulation of MDM2. (C) 2010 Published by Elsevier Inc.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available