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Mdm2 affects genome stability independent of p53 Bouska A; Eischen CMCancer Res 2009[Mar]; 69 (5): 1697-701Mdm2 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.|*Genomic Instability[MESH]|Animals[MESH]|Cell Cycle Proteins/physiology[MESH]|Cell Transformation, Neoplastic[MESH]|DNA Breaks, Double-Stranded[MESH]|DNA Repair[MESH]|Humans[MESH]|Neoplasms/*etiology/genetics[MESH]|Nuclear Proteins/physiology[MESH]|Proto-Oncogene Proteins c-mdm2/*physiology[MESH]|Tumor Suppressor Protein p53/*physiology[MESH] |
