The stress-responsive gene ATF3 regulates the histone acetyltransferase Tip60

Hongmei Cui, Mingxiong Guo, Dong Xu, Zhi-Chun Ding, Gang Zhou, Hanfei Ding, Junran Zhang, Yi Tang, Chunhong Yan

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Tat-interactive protein 60 (Tip60) is a MYST histone acetyltransferase that catalyses acetylation of the major DNA damage kinase Ataxia telangiectasia mutated (ATM), thereby triggering cellular signalling required for the maintenance of genomic stability on genotoxic insults. The Tip60 activity is modulated by post-translational modifications that alter its stability and its interactions with substrates. Here we report that activating transcription factor 3 (ATF3), a common stress mediator and a p53 activator, is a regulator of Tip60. ATF3 directly binds Tip60 at a region adjacent to the catalytic domain to promote the protein acetyltransferase activity. Moreover, the ATF3-Tip60 interaction increases the Tip60 stability by promoting USP7-mediated deubiquitination of Tip60. Consequently, knockdown of ATF3 expression leads to decreased Tip60 expression and suppression of ATM signalling as evidenced by accumulated DNA lesions and increased cell sensitivity to irradiation. Our findings thus reveal a previously unknown function of a common stress mediator in regulating Tip60 function.

Original languageEnglish (US)
Article number6752
JournalNature communications
Volume6
DOIs
StatePublished - Apr 13 2015

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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