Title

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

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Date

7-18-2008

Document Type

Article

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

Disciplines

Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Therapeutics

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.

Rights and Permissions

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.

Comments

At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.

Related Resources

Link to Article in PubMed