Histone Arg modifications and p53 regulate the expression of OKL38, a mediator of apoptosis

Hongjie Yao, Pingxin Li, Bryan J. Venters, Suting Zheng, Paul R. Thompson, B. Franklin Pugh, Yanming Wang

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

Abstract

Protein Arg methyltransferases function as coactivators of the tumor suppressor p53 to regulate gene expression. Peptidylarginine deiminase 4 (PAD4/PADI4) counteracts the functions of protein Arg methyltransferases in gene regulation by deimination and demethylimination. Here we show that the expression of a tumor suppressor gene, OKL38, is activated by the inhibition of PAD4 or the activation of p53 following DNA damage. Chromatin immunoprecipitation assays showed a dynamic change of p53 and PAD4 occupancy and histone Arg modifications at the OKL38 promoter during DNA damage, suggesting a direct role of PAD4 and p53 in the expression of OKL38. Furthermore, we found that OKL38 induces apoptosis through localization to mitochondria and induction of cytochrome c release. Together, our studies identify OKL38 as a novel p53 target gene that is regulated by PAD4 and plays a role in apoptosis.

Original languageEnglish (US)
Pages (from-to)20060-20068
Number of pages9
JournalJournal of Biological Chemistry
Volume283
Issue number29
DOIs
StatePublished - Jul 18 2008

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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