| Title | Acetylation of FoxO1 Activates Bim Expression to Induce Apoptosis in Response to Histone Deacetylase Inhibitor Depsipeptide Treatment |
| Authors | Yang, Yang Zhao, Ying Liao, Wenjuan Yang, Jing Wu, Lipeng Zheng, Zhixing Yu, Yu Zhou, Wen Li, Lian Jingnan, Feng Wang, Haiying Zhu, Wei-Guo |
| Affiliation | Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China. Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, 38 Xueyuan Rd, Beijing 100191, Peoples R China. |
| Keywords | PROAPOPTOTIC PROTEIN BIM CANCER CELL-LINES TRANSCRIPTION FACTORS BCL-2 FAMILY TUMOR SUPPRESSION DNA-BINDING LIFE-SPAN MEMBER SURVIVAL GENE |
| Issue Date | 2009 |
| Publisher | neoplasia |
| Citation | NEOPLASIA.2009,11,(4),313-U15. |
| Abstract | Histone deacetylase (HDAC) inhibitors have been shown to induce cell cycle arrest and apoptosis in cancer cells. However, the mechanisms of HDAC inhibitor induced apoptosis are incompletely understood. In this study, depsipeptide, a novel HDAC inhibitor, was shown to be able to induce significant apoptotic cell death in human lung cancer cells. Further study showed that Bim, a BH3-only proapoptotic protein, was significantly upregulated by depsipeptide in cancer cells, and Bim's function in depsipeptide-induced apoptosis was confirmed by knockdown of Bim with RNAi. In addition, we found that depsipeptide-induced expression of Bim was directly dependent on acetylation of forkhead box class O1 (FoxO1) that is catalyzed by cyclic adenosine monophosphate-responsive element-binding protein-binding protein, and indirectly induced by a decreased four-and-a-half LIM-domain protein 2. Moreover, our results demonstrated that FoxO1 acetylation is required for the depsipeptide-induced activation of Bim and apoptosis, using transfection with a plasmid containing FoxO1 mutated at lysine sites and a luciferase reporter assay. These data show for the first time that an HDAC inhibitor induces apoptosis through the FoxO1 acetylation-Bim pathway. |
| URI | http://hdl.handle.net/20.500.11897/246392 |
| ISSN | 1522-8002 |
| DOI | 10.1593/neo.81358 |
| Indexed | SCI(E) |
| Appears in Collections: | 医学部待认领 |
