Edinburgh Research Explorer

PHD3 regulates p53 protein stability by hydroxylating Proline 359

Research output: Contribution to journalArticlepeer-review

Related Edinburgh Organisations

Open Access permissions

Open

Documents

Original languageEnglish
JournalCell Reports
DOIs
Publication statusPublished - 31 Jul 2018

Abstract

Cellular p53 protein levels are regulated by an ubiquitination/de-ubiquitination cycle which can target the protein for proteasomal destruction. The ubiquitination reaction is catalysed by a multitude of ligases, whereas the removal of ubiquitin chains is mediated by two deubiquitinating enzymes (DUBs), USP7 (HAUSP) and USP10. Here we show that PHD3 hydroxylates p53 at proline-359, a residue that is in the p53-DUB binding domain. Hydroxylation of p53 upon proline-359 regulates its interaction with USP7 and USP10 and its inhibition decreases the association of p53 with USP7/USP10, increases p53 ubiquitination and rapidly reduces p53 protein levels independently of mRNA expression. Our results show that p53 is a PHD3 substrate and that hydroxylation by PHD3 regulates p53 protein stability through modulation of ubiquitination.

Download statistics

No data available

ID: 66199527