Acetylation of PML is involved in histone deacetylase inhibitor-mediated apoptosis.
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Hayakawa F, Abe A, Kitabayashi I, Pandolfi PP, Naoe T
Acetylation of PML is involved in histone deacetylase inhibitor-mediated apoptosis.
J Biol Chem. 2008 Sep 5;283(36):24420-5. doi: 10.1074/jbc.M802217200. Epub 2008 Jul 11.
- PubMed ID
- 18621739 [ View in PubMed]
- Abstract
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.