Journal
EMBO REPORTS
Volume 10, Issue 2, Pages 166-172Publisher
WILEY
DOI: 10.1038/embor.2008.231
Keywords
MDM2; p53; RYBP; ubiquitination; human cancer
Categories
Funding
- National Institutes of Health (NIH) [R01 CA112029, R01 CA121211]
- Department of Defense (DoD) [W81XWH-06-1-0063]
- NIH/University of Alabama at Birmingham (UAB) Gene Therapy Center [CA075930]
- Ministry of Science and Technology of China [2007CB947100]
- National Natural Science Foundation of China [30870513]
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The mouse double minute 2 (MDM2)-p53 interaction regulates the activity of p53 and is a potential target for human cancer therapy. Here, we report that RYBP (RING1- and YY1-binding protein), a member of the polycomb group (PcG), interacts with MDM2 and decreases MDM2-mediated p53 ubiquitination, leading to stabilization of p53 and an increase in p53 activity. RYBP induces cell-cycle arrest and is involved in the p53 response to DNA damage. Expression of RYBP is decreased in human cancer tissues compared with adjacent normal tissues. These results show that RYBP is a new regulator of the MDM2-p53 loop and that it has tumour suppressor activity.
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