Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53

TLDR

The tumor suppressor p53 is degraded by the ubiquitin‑proteasome system. The study demonstrates that MDM2 acts as a ubiquitin ligase E3, polyubiquitinating p53 via a sulfhydroxy bond and requiring a cysteine residue, thereby revealing its role in degrading p53 in HPV‑uninfected cells lacking E6.

Abstract

The tumor suppressor p53 is degraded by the ubiquitin-proteasome system. p53 was polyubiquitinated in the presence of E1, UbcH5 as E2 and MDM2 oncoprotein. A ubiquitin molecule bound MDM2 through sulfhydroxy bond which is characteristic of ubiquitin ligase (E3)-ubiquitin binding. The cysteine residue in the carboxyl terminus of MDM2 was essential for the activity. These data suggest that the MDM2 protein, which is induced by p53, functions as a ubiquitin ligase, E3, in human papillomavirus-uninfected cells which do not have E6 protein.