EDD Inhibits ATM-mediated Phosphorylation of p53*

Abstract

The EDD (E3 identified by differential display) gene, first identified as a progestin-induced gene in T-47D breast cancer cells, encodes an E3 ubiquitin ligase with a HECT domain. It was reported that EDD is involved in the G2/M progression through ubiquitination of phospho-katanin p60. Previous study has also shown that EDD can act as a transcription cofactor independently of its E3 ligase activity. In this study, we uncover a new role for EDD during cell cycle progression in an E3 ligase-independent manner. We demonstrate that EDD can physically interact with p53 and that this interaction blocks the phosphorylation of p53 by ataxia telangiectasia mutated (ATM). Silencing of EDD induces phosphorylation of p53 at Ser15 and activates p53 target genes in fibroblasts and some transformed cells without activation of DNA damage response. The G1/S arrest induced by EDD depletion depends on p53. On the other hand, overexpression of EDD inhibits p53-Ser15 phosphorylation and suppresses the induction of p53 target genes during DNA damage, and this effect does not require its E3 ligase activity. Thus, through binding to p53, EDD actively inhibits p53 phosphorylation by ATM and plays a role in ensuring smooth G1/S progression

Similar works

Full text

PubMed CentralProvided a free PDF (195.62 KB)

3083215oai:pubmedcentral.nih.gov:3083215
Last time updated on July 8, 2012View original full text link

This paper was published in PubMed Central.

Having an issue?

Is data on this page outdated, violates copyrights or anything else? Report the problem now and we will take corresponding actions after reviewing your request.