Title

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

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date

7-18-2008

Document Type

Article

Subjects

*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.

DOI of Published Version

10.1074/jbc.M802940200

Source

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.

Journal/Book/Conference Title

The Journal of biological chemistry

Comments

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

Related Resources

Link to Article in PubMed