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  • Title: Transcriptional induction of protein kinase C delta by p53 tumor suppressor in the apoptotic response to DNA damage.
    Author: Dashzeveg N, Yogosawa S, Yoshida K.
    Journal: Cancer Lett; 2016 Apr 28; 374(1):167-174. PubMed ID: 26884258.
    Abstract:
    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 (PKCδ) also induces apoptosis via various mechanisms including modification of p53. The PKCδ-dependent apoptotic mechanism has been extensively studied; however, the transcriptional regulation of PKCδ remains obscure. The current study demonstrates the transcriptional regulation of PKCδ by p53 upon genotoxic stress. The p53-binding site in the promoter region of PKCδ was detected by the ChIP-sequencing assay. Notably, the expression of PKCδ 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 PKCδ disturbed p53-promoted PKCδ expression and suppressed apoptosis following DNA damage. Thus, our findings suggest that the transcriptional regulation of PKCδ is controlled by p53 in a positive feedback mechanism to induce apoptosis in response to DNA damage.
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