Mdm2 Affects Genome Stability Independent of p53

¹Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska and ²Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee

^* To whom correspondence should be addressed. E-mail: christine.eischen{at}vanderbilt.edu.

	Abstract

Mdm2 is a critical negative regulator of the p53 tumor suppressor and is frequently overexpressed in human cancers. However, reports, including our own studies, suggest that Mdm2 has both p53-dependent and p53-independent functions that contribute to genomic instability and transformation when deregulated. We recently elucidated a p53-independent role for Mdm2 in the regulation of the DNA double-strand break repair response, genomic stability, and transformation through interaction with Nbs1, a member of the Mre11/Rad50/Nbs1 DNA double-strand break repair complex. In light of these findings, targeting Mdm2 in human malignancies may have effects other than activating p53. [Cancer Res 2009;69(5):1697–701]

Key Words: genome stability, Mdm2, p53