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Tip60 is targeted to proteasome‐mediated degradation by Mdm2 and accumulates after UV irradiation
Author(s) -
Legube Gaëlle,
Linares Laetitia K.,
Lemercier Claudie,
Scheffner Martin,
Khochbin Saadi,
Trouche Didier
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/21.7.1704
Subject(s) - biology , ubiquitin ligase , ubiquitin , proteasome , mdm2 , histone , chromatin , acetylation , microbiology and biotechnology , proteolysis , nuclear protein , dna damage , histone acetyltransferases , dna repair , transcription factor , apoptosis , biochemistry , dna , enzyme , gene
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 γ 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.