Response of p53 to DSBs generated by ionizing radiation

Response of p53 to DSBs generated by ionizing radiation. Activated p53 can induce cell cycle arrest at the G1, S and G2 phases, trigger apoptosis or force a cell into cellular senescence. Stabilization of p53 protein is mediated by multiple phosphorylations on p53 and Mdm2 via the ATM/ATR and Chk1/2 kinases. p53-mediated transcription of p21 inhibits both cyclin D-cdk4/6 (G1 arrest) and cyclin E/A-cdk2 (S-phase arrest). Cyclin-cdk inhibition allows unphosporylated Rb to sequester E2F necessary for transition into S phase. Prolonged p53 activation may lead to chromatin remodeling and permanent cell cycle arrest (senescence). p53-mediated transcription of 14-3-3s and Gadd45 inhibit cyclin B-cdc2 (G2 arrest). Prolonged p53 activation can also trigger apoptosis through transcription of proapoptic proteins bax, noxa and puma. p53-mediated transription of DRAM can lead to cell macroautophagy.

Publication

Radiosensitization of Prostate Cancer by Priming the Wild-type p53-Dependent Cellular Senescence Pathway. () Brian D. Lehmann, et al. Cancer Biol Ther. ;6(8):1165-1170. Figure: F1. All organisms Homo sapiens Drosophila melanogaster

Disease mentions