PHD3 regulates p53 protein stability by hydroxylating Proline 359

Javier Rodriguez, Ana Herrero, Shuijie Li, Nora Rauch, Andrea Quintanilla, Kieran Wynne, Aleksander Krstic, Juan Carlos Acosta, Cormac Taylor, Susanne Schlisio, Alex von Kriegsheim

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
JournalCell Reports
DOIs
Publication statusPublished - 31 Jul 2018

Fingerprint

Dive into the research topics of 'PHD3 regulates p53 protein stability by hydroxylating Proline 359'. Together they form a unique fingerprint.

Cite this