2. Academic Validation
  3. The stress-responsive gene ATF3 regulates the histone acetyltransferase Tip60

The stress-responsive gene ATF3 regulates the histone acetyltransferase Tip60

  • Nat Commun. 2015 Apr 13;6:6752. doi: 10.1038/ncomms7752.
Hongmei Cui 1,  Mingxiong Guo 2,  Dong Xu 2,  Zhi-Chun Ding 3,  Gang Zhou 4,  Han-Fei Ding 5,  Junran Zhang 6,  Yi Tang 2,  Chunhong Yan 7
Affiliations

Affiliations

  • 1 1] GRU Cancer Center, Georgia Regents University, 1120 15th Street, Augusta, Georgia 30912, USA [2] Center for Cell Biology and Cancer Research, Albany Medical College, 47 New Scotland Avenue, Albany, New York 12208, USA.
  • 2 Center for Cell Biology and Cancer Research, Albany Medical College, 47 New Scotland Avenue, Albany, New York 12208, USA.
  • 3 GRU Cancer Center, Georgia Regents University, 1120 15th Street, Augusta, Georgia 30912, USA.
  • 4 1] GRU Cancer Center, Georgia Regents University, 1120 15th Street, Augusta, Georgia 30912, USA [2] Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, 1120 15th Street, Augusta, Georgia 30912, USA.
  • 5 1] GRU Cancer Center, Georgia Regents University, 1120 15th Street, Augusta, Georgia 30912, USA [2] Department of Pathology, Georgia Regents University, 1120 15th Street, Augusta, Georgia 30912, USA.
  • 6 Department of Radiation Oncology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA.
  • 7 1] GRU Cancer Center, Georgia Regents University, 1120 15th Street, Augusta, Georgia 30912, USA [2] Center for Cell Biology and Cancer Research, Albany Medical College, 47 New Scotland Avenue, Albany, New York 12208, USA [3] Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, 1120 15th Street, Augusta, Georgia 30912, USA.
PMID: 25865756 DOI: 10.1038/ncomms7752
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.

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