Histone Arg modifications and p53 regulate the expression of OKL38, a mediator of apoptosis
Histone Arg modifications and p53 regulate the expression of OKL38, a mediator of apoptosis
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DOI：
10.1074/jbc.m802940200
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发表时间：
2008-07-18
影响因子：
4.8
通讯作者：
Wang, Yanming
中科院分区：
文献类型：
--
作者：
Yao, Hongjie;Li, Pingxin;Wang, Yanming
蛋白质Arg甲基转移酶作为肿瘤抑制因子p53的共激活物来调节基因表达。肽基精氨酸脱亚胺酶4（PAD 4/PADI 4）通过脱亚胺化和脱甲基亚胺化来抵消蛋白质精氨酸甲基转移酶在基因调控中的功能。在这里，我们表明，表达的肿瘤抑制基因，OKL 38，被激活的抑制PAD 4或激活p53的DNA损伤后。染色质免疫沉淀分析显示，在DNA损伤过程中，OKL 38启动子的p53和PAD 4占据率和组蛋白Arg修饰发生动态变化，表明PAD 4和p53在OKL 38表达中起直接作用。此外，我们发现OKL 38通过定位于线粒体和诱导细胞色素c释放来诱导细胞凋亡。总之，我们的研究确定OKL 38作为一种新的p53靶基因，由PAD 4调节，并在细胞凋亡中发挥作用。
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.