p53 regulation by ubiquitin and ubiquitin-like modifications

Abstract

The tumor suppressor p53 plays a central role in stress responses and tumor suppression. The increasingly complex p53 network is controlled by multiple layers of mechanisms, including the genetic level, transcriptional level, and protein level. Post-translational modifications (PTMs) of p53 represent a precise and efficient form of regulation. To date, the modification of p53 by ubiquitin and ubiquitin-like proteins (UBLs) has been studied extensively, including SUMOylation, NEDDylation, FATylation, ISGylation, and the recently identified UFMylation. They affect p53 stability, conformation, localization, transcriptional activity and binding partners. Here, we review these recent discoveries and summarize our understanding of ubiquitination and UBL modifications of p53 to better comprehend the complex landscape of p53 regulation. We will discuss how the ubiquitination and UBL modifications of p53 dynamically adjust its function to respond to various stress stimuli, thereby determining cell fate.

Funding

National Natural Science Foundation of China(81871116)