Tip60 is targeted to proteasome-mediated degradation by Mdm2 and accumulates after UV irradiation

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...

Full description

Saved in:
Bibliographic Details
Published in:The EMBO journal 2002-04, Vol.21 (7), p.1704-1712
Main Authors: Legube, Gaëlle, Linares, Laetitia K., Lemercier, Claudie, Scheffner, Martin, Khochbin, Saadi, Trouche, Didier
Format: Article
Language:English
Subjects:
Acetyltransferases
Acetyltransferases - genetics
Acetyltransferases - metabolism
Amino Acid Sequence
Animals
Biochemistry, Molecular Biology
Cysteine Endopeptidases
EMBO13
EMBO31
Gene Expression
HeLa Cells
histone acetyltransferase
Histone Acetyltransferases
Humans
Irradiation
Life Sciences
Ligases
Ligases - metabolism
Lysine Acetyltransferase 5
Mdm2
Mdm2 protein
Mice
Molecular Sequence Data
Multienzyme Complexes
Multienzyme Complexes - antagonists & inhibitors
Nuclear Proteins
proteasome
Proteasome Endopeptidase Complex
proteasomes
Proto-Oncogene Proteins
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-mdm2
Tip60
Tip60 protein
Tumor Cells, Cultured
Ubiquitin
Ubiquitin - metabolism
Ubiquitin-Protein Ligases
ubiquitylation
Ultraviolet radiation
Ultraviolet Rays
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0261-4189
1460-2075
1460-2075
DOI:10.1093/emboj/21.7.1704