Acetylation of PML is involved in histone deacetylase inhibitor-mediated apoptosis
Acetylation of PML is involved in histone deacetylase inhibitor-mediated apoptosis
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DOI：
10.1074/jbc.m802217200
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发表时间：
2008-09-05
影响因子：
4.8
通讯作者：
Naoe, Tomoki
中科院分区：
文献类型：
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作者：
Hayakawa, Fumihiko;Abe, Akihiro;Naoe, Tomoki
PML是一种有效的肿瘤抑制因子和促凋亡因子，在功能上受磷酸化、sumo化和泛素化等翻译后修饰的调节。组蛋白去乙酰化酶（HDAC）抑制剂是一类很有前途的靶向抗癌药物，其诱导癌细胞凋亡的机制尚不清楚。我们在这里报告了一种新的转录后修饰，乙酰化，PML。在HeLa细胞中，PML作为一种乙酰化蛋白存在，通过p300的共表达或HDAC抑制剂trichostatin a的处理，PML的乙酰化增强，PML乙酰化的增加与体外和体内PML的sumo化增加相关。PML参与曲古霉素a诱导的细胞凋亡，乙酰化缺陷突变的PML无法介导细胞凋亡，提示PML乙酰化的重要性。我们的工作为通过翻译后修饰调控PML提供了新的见解，并为HDAC抑制剂的治疗机制提供了新的信息。
PML is a potent tumor suppressor and proapoptotic factor and is functionally regulated by post-translational modifications such as phosphorylation, sumoylation, and ubiquitination. Histone deacetylase (HDAC) inhibitors are a promising class of targeted anticancer agents and induce apoptosis in cancer cells by largely unknown mechanisms. We report here a novel post-transcriptional modification, acetylation, of PML. PML exists as an acetylated protein in HeLa cells, and its acetylation is enhanced by coexpression of p300 or treatment with a HDAC inhibitor, trichostatin A. Increased PML acetylation is associated with increased sumoylation of PML in vitro and in vivo. PML is involved in trichostatin A-induced apoptosis and PML with an acetylation-defective mutation shows an inability to mediate apoptosis, suggesting the importance of PML acetylation. Our work provides new insights into PML regulation by post-translational modification and new information about the therapeutic mechanism of HDAC inhibitors.