Abstract 2983: Che-1 promotes tumor cell survival by sustaining mutant p53 transcription and inhibiting DNA damage response activation

Abstract Che-1 is a RNA polymerase II binding protein involved in the regulation of gene transcription, and in response to DNA damage promotes p53 transcription. In this study, we investigated whether Che-1 regulates mutant p53 expression. We found that Che-1 is required for sustaining mutant p53 expression in several cancer cell lines, and Che-1 depletion by siRNA induces apoptosis both in vitro and in vivo. Notably, loss of Che-1 activates DNA damage checkpoint response and induces transactivation of p73. Therefore, these findings suggest a new therapeutic approach that allowing simultaneous modulation of p73 and mutant p53 levels might be used to target the large fraction of human tumors harboring p53 mutations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2983.