NF-κB RelA opposes epidermal proliferation driven by TNFR1 and JNK (original) (raw)

1. Jennifer Y. Zhang,
2. Cheryl L. Green,
3. Shiying Tao, and
4. Paul A. Khavari1
5. VA Palo Alto Healthcare System, Palo Alto, California 94305, USA; Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA

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.

• Epidermis
• NF-κB
• proliferation
• differentiation

Footnotes

• Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1160904.

• Supplemental material is available at http://www.genesdev.org.

• 1
  ↵1 Corresponding author.
  ↵1 E-MAIL khavari{at}CMGM.stanford.edu; FAX (650) 723-8762.

• • Accepted November 19, 2003.
  • Received October 14, 2003.

• Cold Spring Harbor Laboratory Press

•