NF-κB/RelA signaling required for CD40-induced humoral immunity depends on specific NEMO lysine residues in mice

ABSTRACT: Oxidative stress and genotoxic damage activate NF-κB signaling through intracellular pathways distinct from those initiated by membrane receptors. Both DNA damage and reactive oxygen species selectively induce post-translational modifications at lysine residues 277 and 309 of the human ubiquitin-binding protein NEMO to promote NF-κB signaling, but the physiological importance of these modifications in vivo remains unclear. Here, we show that a newly developed mouse model (NEMODK) carrying germline arginine substitutions of the corresponding NEMO lysine residues exhibits B-cell-intrinsic defects in germinal center formation and anti-viral humoral responses. Mechanistically, we identify in NEMODK B-cells a CD40-specific NF-κB signaling defect that is not linked to the well-characterized cano

SUBMITTER: Donna Li 

PROVIDER: S-SCDT-10_1038-S44318-026-00875-0 | biostudies-other |

REPOSITORIES: biostudies-other