Differential Regulation of BBC3 / PUMA and PMAIP1 / Noxa by Ionizing Radiation: A Role for p53

Authors: Kuchur О.А.Chesnokova P.D., Daria Kuzmina , Alexander Zavirsky, Shtil A. A.

The p53 transcription factor is the most important sensor of ionizing radiation. Among the numerous effectors of p53 are the genes BBC3 and PMAIP1 encoding proapoptotic proteins PUMA and Noxa, respectively, as well as the CDKN1A/p21 cell cycle inhibitor. The effectiveness of radiation exposure— whether there is cell death or survival—is determined by the balance of mechanisms regulated by these proteins. In the present work, the predominant role was shown of BBC3/PUMA and CDKN1A/p21 versus PMAIP1/Noxa in p53-mediated responses to therapeutic doses of γ-radiation on isogenic human tumor cell lines (HCT116 colorectal carcinoma and HCT116p53KO subline with nonfunctioning p53). Bioinformatics analysis of genome-wide nucleotide sequences revealed significant differences in the putative motifs of p53 binding in the structure of genes BBC3 and PMAIP1. The results obtained are important for the development of targeted effects that would allow preserving the p53-dependent activation of proapoptotic genes while limiting the blocking of the cell cycle in irradiated tumor cells.

 

doi: 10.1134/S1990519X21060043