NF-κB RelA opposes epidermal proliferation driven by TNFR1 and JNK
Open Access
- 1 January 2004
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 18 (1) , 17-22
- https://doi.org/10.1101/gad.1160904
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.Keywords
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