title: Transcription factor Sox4 is required for PUMA-mediated apoptosis induced by histone deacetylase inhibitor, TSA.
abstract: PUMA is a crucial regulator of apoptotic cell death mediated by p53-dependent and p53-independent mechanisms. In many cancer cells, PUMA expression is induced in response to DNA-damaging reagent in a p53-dependent manner. However, few studies have investigated transcription factors that lead to the induction of PUMA expression via p53-independent apoptotic signaling. In this study, we found that the transcription factor Sox4 increased PUMA expression in response to trichostatin A (TSA), a histone deacetylase inhibitor in the p53-null human lung cancer cell line H1299. Ectopic expression of Sox4 led to the induction of PUMA expression at the mRNA and protein levels, and TSA-mediated up-regulation of PUMA transcription was repressed by the knockdown of Sox4. Using luciferase assays and chromatin immunoprecipitation, we also determined that Sox4 recruits p300 on the PUMA promoter region and increases PUMA gene expression in response to TSA treatment. Taken together, these results suggest that Sox4 is required for p53-independent apoptotic cell death mediated by PUMA induction via TSA treatment.
authors.affiliation: Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Jang
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Kang
authors.forename: Jung-Woong
authors.initials: JW
authors.lastname: Kim
authors.forename: Chul-Hong
authors.initials: CH
authors.lastname: Kim
authors.forename: Joo-Hee
authors.initials: JH
authors.lastname: An
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Choi
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D055751:SOXC Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D011518:Proto-Oncogene Proteins; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C012589:trichostatin A
keywords: DBD; DNA binding domain; PUMA; TAD; TSA; Target gene; Transcription factor Sox4; p53-Independent apoptotic cell death; transactivation domain; trichostatin A