Abstract 4950: Discovery of the pro-apoptotic genes induced by tumor suppressor p53

Abstract

Abstract The tumor suppressor p53 regulates apoptosis in response to DNA damage. Promoter selectivity of p53 depends mainly on its phosphorylation. Notably, the phosphorylation at serine-46 (Ser46) of p53 is indispensable to promote pro-apoptotic genes. However, little is known about the pro-apoptotic genes induced by Ser46 phosphorylation of p53. In our study, we aimed to investigate pro-apoptotic genes induced by p53 using microarray analysis and ChIP sequencing assay. Although microarray analysis became common tool in molecular biology, novelty of our research is combining microarray analysis with ChIP sequencing assay to discover direct target of p53 in Ser46 specific manner. Analyze of microarray showed specific up-regulation of 2723 genes in wild type p53 (wt-p53). Alternatively, 1338 genes were interacted directly with only wt-p53 but not with mutant p53 (Ser46 is substituted with alanine, p53S46A) in ChIP sequencing assay. The comparison of two assays, microarray analysis and ChIP sequencing assay, investigated thirty genes in relation with Ser46 phosphorylation of tumor suppressor p53. Those thirty genes were clarified by real time RT-PCR and the genes strongly elicited were chosen further study. The research will be continued with more clarification and apoptotic function of candidate genes in response to DNA damage will be investigated. We hope that the discovery of pro-apoptotic genes induced by p53 will convey the important role in cancer research and therapy. Acknowledgement: This project is partly supported by Global Center of Excellence (GCOE) program at TMDU. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4950. doi:1538-7445.AM2012-4950