Mdm2 affects genome stability independent of p53.
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.
Bouska
Alyssa
A
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, USA.
Eischen
Christine M
CM
D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D042822:Genomic Instability; D006801:Humans; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics; D009687:Nuclear Proteins / Q000502:physiology; D051736:Proto-Oncogene Proteins c-mdm2 / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2