ATM phosphorylates ZBP-89 at Ser202 to potentiate p21waf1 induction by butyrate

Longchuan Bai, Juanita L. Merchant

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Histone deacetylase inhibitors (HDACi) induce growth arrest and differentiation, particularly in the colon where they are potential chemotherapeutic agents. A key mediator of HDACi action is the cyclin dependent kinase (CDK) inhibitor p21waf1. HDACi treatment of colonic cells promotes the formation of an ATM/ZBP-89/p300 complex on p21waf1 proximal promoter, and this multi-molecular complex plays an important role in HDACi induction of p21waf1 expression in vitro and mucosal protection in vivo. Here we found that ZBP-89 is phosphorylated by ATM kinase in vitro and in vivo. Disruption of the ATM phosphorylation motif 202SQ within the zinc finger domain of ZBP-89 attenuated its ability to enhance p21waf1 activation by butyrate. Moreover, disruption of the ATM phosphorylation site abrogated the ability of ZBP-89 to potentiate butyrate induction of endogenous p21waf1 expression. These results demonstrate that ATM phosphorylation of ZBP-89 contributes to HDACi induction of p21waf1 gene expression.

Original languageEnglish (US)
Pages (from-to)817-821
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume359
Issue number3
DOIs
StatePublished - Aug 3 2007
Externally publishedYes

Keywords

  • Acetylation
  • Histone deacetylase inhibitor
  • Phosphorylation
  • Trichostatin A
  • ZNF148

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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