Non-canonical functions of the MDM2 oncoprotein

Abstract

The tumour suppressor gene TP53 is mutated in ~50% of human cancers. The p53 protein is a transcription factor which is induced by several cellular stresses, such as ribosomal stress and DNA damage. Expression of its target genes leads to cell cycle arrest, apoptosis, or senescence. MDM2 is one of these target genes and acts as a negative regulator by binding to p53, leading to its proteasomal degradation and inhibition. MDM2 and p53 are thus linked by a negative feedback loop which provides cells with an additional layer of regulation. In recent years, several non-canonical functions of the E3 ubiquitin ligase MDM2 2. MANUSCRIPT 1 MDM2, in a complex with the ribosomal proteins L5 and L11, inhibits RNA Polymerase III and induces nucleolar stress.