Open AccessActivation of the atypical NF-κB pathway induced by ionizing radiation is not affected by the p53 status
Author(s) -
Gracjana Zając,
Marek Rusin,
Barbara Łasut-Szyszka,
Krzysztof Puszyński,
Piotr Widłak
Publication year - 2022
Publication title -
acta biochimica polonica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.452
H-Index - 78
eISSN - 1734-154X
pISSN - 0001-527X
DOI - 10.18388/abp.2020_5942
Subject(s) - phosphorylation , nf κb , ionizing radiation , iκbα , signal transduction , transcription factor , p50 , cancer research , iκb kinase , transcription (linguistics) , chemistry , protein subunit , cytokine , nfkb1 , gene , microbiology and biotechnology , biology , genetics , biochemistry , irradiation , physics , linguistics , philosophy , nuclear physics
DNA double-strand breaks induced by ionizing radiation can activate the atypical NF-κB pathway via ATM-mediated phosphorylation of NEMO/IKKγ. We aimed to determine whether the status of p53 influenced the activation of this particular NF-κB pathway. The NF-κB signaling was activated either by irradiation with a single 8 Gy dose or by TNFα cytokine in p53-proficient and p53-deficient variants of HCT116, RKO, and U2-OS human cancer cell lines. To assess pathway activation the kinetics of phosphorylation (Ser32) and proteolytic degradation of IκBα inhibitor and phosphorylation (Ser536) of RelA(p65) NF-κB subunit were analyzed. Though activation of the radiation-induced atypical pathway was delayed and weakened when compared to the cytokine-induced canonical pathway, no significant differences were noted between p53-proficient and p53-deficient variants, which indicated that activation of both NF-κB pathways was not affected by the p53 status. In marked contrast, the presence of p53 significantly affected downstream effects of NF-κB activation, i.e. transcription of NF-κB-dependent genes. However, different patterns of such interference were observed, which indicated gene-specific and cell-specific mechanisms of interactions between NF-κB and p53 at the transcription regulation level.