MDM2

Murine double minute-2. A gene that encodes a 90-kD nuclear phosphoprotein with a binding site for the tumour suppressor p53. Once a MDM2-p53 complex is formed, p53 activity is rapidly down-regulated and p53 is degraded by a ubiquitin-proteasome pathway. MDM2 inhibits p53 activity by inhibiting transfer of p53 from cytoplasm to nucleus, blocking p53-DNA interaction and, by ubiquitinising p53, inhibits apoptosis. These actions, coupled with CDK4 inhibition of RB1 by phosphorylation, release the G1-S checkpoint. MDM2 and CDK4 amplification occurs in a range of carcinomas and sarcomas—especially liposarcomas and haemopoietic neoplasia. MDM2 protein expression is a negative prognostic marker in breast carcinoma.