The MDM2 gene encodes a protein that acts as an E3 ubiquitin ligase.  Localized in the nucleus, this protein has a key pathological role as it can promote tumor formation by targeting tumor suppressor proteins such as p53.  It does this by forming a negative auto-regulatory feedback loop with p53.  MDM2 binds to p53 and inhibits p53-mediated transactivation.  As an E3 ubiquitin ligase, it also causes the ubiquitination and subsequent degradation of p53 by the proteasome.

Overexpression or amplification of the MDM2 gene has been detected in a variety of different cancers.   Additionally, it has been associated with susceptibility to Accelerated Tumor Formation (ACTFS). 

The MDM2 gene is located on the long arm of chromosome 12.  It spans a length of about 42 kb and consists of 13 exons.  The protein encoded by the gene has a mass of 55 kDa and is made up of 491 amino acids.  Several isoforms of the protein exist due to alternative splicing.  However, most of these isoforms are only expressed in tumor cells.  The MDM2 SNP, c.410T>G, called SNP309 due to its position at the 309th nucleotide of intron 1, has been of particular interest in cancer studies.  It has been associated with ACTFS in both hereditary and sporadic cases of cancer.  However, certain studies have also found it to be protective against cancer.