Overview:

MDM2 is a nuclear phosphoprotein that binds and inhibits transactivation by p53, as part of an autoregulatory negative feedback loop (1). Overexpression of the MDM2 gene product can lead to excessive inactivation of p53 thereby diminishing its tumor suppressor function. The inactivation of p53 is mediated by the E3 ubiquitin ligase activity of MDM2 which targets p53 for proteasomal degradation. MDM2 also affects the cell cycle, apoptosis, and tumorigenesis through interactions with other proteins, including retinoblastoma 1 and ribosomal protein L5 (2). Amplification of MDM2 is frequently observed in human sarcomas and this is consistent with the hypothesis that MDM2 binds to p53 which then leads to escape from p53-regulated growth control.

References:

1. Engel, T. et al: Elevated p53 and lower MDM2 expression in hippocampus from patients with intractable temporal lobe epilepsy. Epilepsy Res. 2007;77(2-3):151-6

2. Liu, G. et al: Genetic polymorphisms of MDM2, cumulative cigarette smoking and nonsmall cell lung cancer risk. Int J Cancer. 2008;122(4):915-8