Histone Arg modifications and p53 regulate the expression of OKL38, a mediator of apoptosis
Venters, Bryan J.
Thompson, Paul R.
Pugh, B. Franklin
UMass Chan AffiliationsDepartment of Biochemistry and Molecular Pharmacology
Cell Line, Tumor
Gene Expression Regulation
Promoter Regions, Genetic
Tumor Suppressor Protein p53
Enzymes and Coenzymes
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AbstractProtein 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.
SourceJ 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.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/50060
At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.
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