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EMBO Rep. 2009 Feb;10(2):166-72. doi: 10.1038/embor.2008.231. Epub 2008 Dec 19.

RYBP stabilizes p53 by modulating MDM2.

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  • 1Department of Pharmacology and Toxicology, University of Alabama at Birmingham, 1670 University Boulevard, Volker Hall 113, Birmingham, Alabama 35294, USA.


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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