biostudies-literaturePhesse TJCancer Research UKWorldwide Cancer ResearchBiotechnology and Biological Sciences Research Council956-66https://www.ebi.ac.uk/biostudies/studies/S-EPMC4013513biostudies-literatureUnknown21(6)Recent studies have suggested that C-MYC may be an excellent therapeutic cancer target and a number of new agents targeting C-MYC are in preclinical development. Given most therapeutic regimes would combine C-MYC inhibition with genotoxic damage, it is important to assess the importance of C-MYC function for DNA damage signalling in vivo. In this study, we have conditionally deleted the c-Myc gene in the adult murine intestine and investigated the apoptotic response of intestinal enterocytes to DNA damage. Remarkably, c-Myc deletion completely abrogated the immediate wave of apoptosis following both ionizing irradiation and cisplatin treatment, recapitulating the phenotype of p53 deficiency in the intestine. Consistent with this, c-Myc-deficient intestinal enterocytes did not upregulate p5Cell death and differentiationEndogenous c-Myc is essential for p53-induced apoptosis in response to DNA damage in vivo.PMC401351315937182741248110-0643Sansom OJPearson HClarke ARVousden KHRidgway RAVassilev LTMyant KBMuncan VSears RPhesse TJCole AMvan den Brink GRfalseEndogenous c-Myc is essential for p53-induced apoptosis in response to DNA damage in vivo.Recent studies have suggested that C-MYC may be an excellent therapeutic cancer target and a number of new agents targeting C-MYC are in preclinical development. Given most therapeutic regimes would combine C-MYC inhibition with genotoxic damage, it is important to assess the importance of C-MYC function for DNA damage signalling in vivo. In this study, we have conditionally deleted the c-Myc gene in the adult murine intestine and investigated the apoptotic response of intestinal enterocytes to DNA damage. Remarkably, c-Myc deletion completely abrogated the immediate wave of apoptosis following both ionizing irradiation and cisplatin treatment, recapitulating the phenotype of p53 deficiency in the intestine. Consistent with this, c-Myc-deficient intestinal enterocytes did not upregulate p52014-01-01T00:00:00Z2014 Jun2025-04-05T13:37:42.073Z2019-03-27T01:27:46ZS-EPMC40135132458364110.1038/cdd.2014.15