Abstract B28: Pro-survival role of p53 in regulating epidermal differentiation

It is well established that in response to diverse stress signals, the p53 tumor suppressor prevents growth of abnormal cells by inducing senescence or apoptosis. However, recent studies have shown that p53 can contribute to pro-survival pathways such as innate immune response, metabolic regulation and antioxidant defense against reactive-oxygen species (ROS). Here we demonstrate a novel role of p53 in regulating an epidermal differentiation program. Using microarray and real-time PCR, we found that p53 activates the expression of genes within the human and mouse epidermal differentiation complex (EDC), including genes within the cornified envelope precursor family and the fused gene family. Chromatin immunoprecipitation and luciferase reporter assay demonstrated direct p53 binding and activation of a cornified envelope precursor gene. Activation of p53 by ultraviolet B (UVB) radiation or via nutlin-3 led to a dose-dependent increase in expression of those genes, and this increase was inhibited in cells with downregulated p53. The p53-dependent expression of the EDC genes was not limited to keratinocytes, but also detected in other cell types, suggesting additional functions of these genes normally attributed to keratinocyte differentiation and formation of the cornified envelope. These findings identify a novel p53-regulated differentiation pathway and suggest that differentiation may be another pro-survival component of its tumor suppressor function. Citation Format: Martina Kracikova, Gal Akiri, Stuart A. Aaronson. Pro-survival role of p53 in regulating epidermal differentiation. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr B28.