Transcriptional induction of protein kinase C delta by p53 tumor suppressor in the apoptotic response to DNA damage

Genetic alterations and aberrant gene expression trigger malignant tumors. Tumor suppressor p53 is the most altered gene in human cancers. p53 induces apoptosis by promoting pro-apoptotic genes in response to DNA damage. Protein kinase C delta (PKC delta) also induces apoptosis via various mechanisms including modification of p53. The PKC delta-dependent apoptotic mechanism has been extensively studied; however, the transcriptional regulation of PKC delta remains obscure. The current study demonstrates the transcriptional regulation of PKC delta by p53 upon genotoxic stress. The p53-binding site in the promoter region of PKC delta was detected by the ChIP-sequencing assay. Notably, the expression of PKC delta was increased upon DNA damage, which is required for the stabilization of p53. More importantly, targeting single guide RNA-driven dead Cas9 to the p53-binding site of PKC delta disturbed p53-promoted PKC delta expression and suppressed apoptosis following DNA damage. Thus, our findings suggest that the transcriptional regulation of PKC delta is controlled by p53 in a positive feedback mechanism to induce apoptosis in response to DNA damage. (C) 2016 Elsevier Ireland Ltd. All rights reserved.