title: NF-kappaB RelA opposes epidermal proliferation driven by TNFR1 and JNK.
abstract: NF-kappaB 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-kappaB 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.
authors.affiliation: VA Palo Alto Healthcare System, Palo Alto, California 94305, USA.
authors.forename: Jennifer Y
authors.initials: JY
authors.lastname: Zhang
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Green
authors.forename: Shiying
authors.initials: S
authors.lastname: Tao
authors.forename: Paul A
authors.initials: PA
authors.lastname: Khavari
mesh_terms: D000818:Animals; D015703:Antigens, CD; D015153:Blotting, Western; D002455:Cell Division / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004622:Embryo, Mammalian; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology; D015603:Keratinocytes / Q000166:cytology* / Q000201:enzymology / Q000502:physiology; D051379:Mice; D016513:Mice, SCID; D016328:NF-kappa B / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors*; D047888:Receptors, Tumor Necrosis Factor, Type I; D012867:Skin / Q000166:cytology / Q000196:embryology; D051996:Transcription Factor RelA
chemical_list: D015703:Antigens, CD; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D051996:Transcription Factor RelA