Tip60 is Targeted to Proteasome-mediated Degradation by Mdm2 and Accumulates After UV Irradiation

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2002 Apr 3

PMID 11927554

Citations 72

Authors

Gaelle Legube

Laetitia K Linares

Claudie Lemercier

Martin Scheffner

Saadi Khochbin

Didier Trouche

Affiliations

Soon will be listed here.

Abstract

Acetylation is a prominent post-translational modification of nucleosomal histone N-terminal tails, which regulates chromatin accessibility. Accordingly, histone acetyltransferases (HATs) play major roles in processes such as transcription. Here, we show that the HAT Tip60, which is involved in DNA repair and apoptosis following gamma irradiation, is subjected to proteasome-dependent proteolysis. Furthermore, we provide evidence that Mdm2, the ubiquitin ligase of the p53 tumour suppressor, interacts physically with Tip60 and induces its ubiquitylation and proteasome-dependent degradation. Moreover, a ubiquitin ligase-defective mutant of Mdm2 had no effect on Tip60 stability. Our results indicate that Mdm2 targets both p53 and Tip60, suggesting that these two proteins could be co-regulated with respect to protein stability. Consistent with this hypothesis, Tip60 levels increased significantly upon UV irradiation of Jurkat cells. Collectively, our results suggest that degradation of Tip60 could be part of the mechanism leading to cell transformation by Mdm2.

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