Putting a finger on growth surveillance: insight into MDM2 zinc finger-ribosomal protein interactions

Abstract

A number of events imparting instability to ribosomal biogenesis can cause nucleolar stress and trigger activation of a p53 checkpoint. Following nucleolar stress, ribosomal proteins L5, L11 and L23 bind to MDM2, blocking MDM2-mediated p53 ubiquitination and degradation. The MDM2 C4 zinc finger domain has been shown to play an important role in this process. Mutations targeting the C4 zinc finger of MDM2 have been reported in human cancers, and now a potential rationale for the occurrence of these mutations in cancer has emerged. Here we further discuss these findings and propose the existence of a ribosomal protein-MDM2-p53 surveillance network responsible for monitoring the stability of the transition between cell growth and division.