Histone Arg modifications and p53 regulate the expression of OKL38, a mediator of apoptosis
Department of Biochemistry and Molecular Pharmacology
Medical Subject Headings
*Apoptosis; Arginine; Cell Line, Tumor; Cytochromes c; DNA Damage; Gene Expression Regulation; Histones; Humans; Hydrolases; Mitochondria; Promoter Regions, Genetic; Protein Transport; Proteins; Tumor Suppressor Protein p53
Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Therapeutics
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.
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Citation: J Biol Chem. 2008 Jul 18;283(29):20060-8. doi: 10.1074/jbc.M802940200. Link to article on publisher's site. Epub 2008 May 22.
Yao, Hongjie; Li, Pingxin; Venters, Bryan J.; Zheng, Suting; Thompson, Paul R.; Pugh, B. Franklin; and Wang, Yanming, "Histone Arg modifications and p53 regulate the expression of OKL38, a mediator of apoptosis" (2008). Thompson Lab Publications. 67.