NF-κB RelA opposes epidermal proliferation driven by TNFR1 and JNK

Abstract

NF-κB inhibition promotes epidermal tumorigenesis; however, whether this reflects an underlying role in homeostasis or a special case confined to neoplasia is unknown. Embryonic lethality of mice lacking NF-κB RelA has hindered efforts to address this. We therefore generated developmentally mature RelA–/– skin. RelA–/– epidermis displays hyperplasia without abnormal differentiation, inflammation, or apoptosis. Hyperproliferation is TNFR1-dependent because Tnfr1 deletion normalized cell division. TNFR1-dependent JNK activation occurred in RelA–/– epidermis, and JNK inhibition abolished hyperproliferation due to RelA deficiency. Thus, RelA antagonizes TNFR1–JNK proliferative signals in epidermis and plays a nonredundant role in restraining epidermal growth.