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

Cancer Letters
Nurmaa DashzevegKiyotsugu Yoshida

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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Citations

May 1, 2016·Cancer Letters·Nurmaa Dashzeveg, Kiyotsugu Yoshida
Nov 28, 2013·PloS One·Siau Jia WeiFarid Ghadessy
Aug 15, 2014·PloS One·Sharon Min Qi CheeFarid J Ghadessy
Sep 8, 2018·Cancer Science·Satomi Yogosawa, Kiyotsugu Yoshida
Jul 6, 2017·Molecular Medicine Reports·Fuqian YangNan Wu
Oct 18, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Magdalena C Liebl, Thomas G Hofmann
Apr 4, 2020·Natural Product Research·Gizele Lucia da Costa PereiraGlenda Nicioli da Silva
Feb 24, 2017·Journal of Biosciences·Daiane Teixeira DE OliveiraGlenda Nicioli DA Silva
Sep 17, 2021·Environmental Toxicology·Jisheng NieQunwei Zhang

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