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

Yao H, Li P, Venters BJ, Zheng S, Thompson PR, Pugh BF, Wang Y
J Biol Chem. 2008 283 (29): 20060-8

PMID: 18499678 · PMCID: PMC2459274 · DOI:10.1074/jbc.M802940200

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.

MeSH Terms (15)

Apoptosis Arginine Cell Line, Tumor Cytochromes c DNA Damage Gene Expression Regulation Histones Humans Hydrolases Mitochondria Promoter Regions, Genetic Protein-Arginine Deiminases Proteins Protein Transport Tumor Suppressor Protein p53

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