These authors contributed equally to this work.
Hairless and NFκB Form a Positive Feedback Loop After UVB and TNFα Stimulation†
Article first published online: 28 MAR 2012
© 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology
Photochemistry and Photobiology
Volume 88, Issue 5, pages 1173–1183, September/October 2012
How to Cite
Casta, A., Kim, H., Luke, C. T., Bachelor, M. A., Engelhard, A., Owens, D. M. and Christiano, A. M. (2012), Hairless and NFκB Form a Positive Feedback Loop After UVB and TNFα Stimulation. Photochemistry and Photobiology, 88: 1173–1183. doi: 10.1111/j.1751-1097.2012.01110.x
This paper is part of the Special Issue in Commemoration of the 70th birthday of Dr. David R. Bickers.
- Issue published online: 5 SEP 2012
- Article first published online: 28 MAR 2012
- Accepted manuscript online: 13 FEB 2012 12:26PM EST
- Received 30 December 2011, accepted 7 February 2012
Hairless (HR) is a nuclear protein with corepressor activity whose exact function in the skin remains to be determined. Mutations in both human and mouse Hairless lead to hair loss accompanied by the appearance of papules, a disorder called atrichia with papular lesions. Furthermore, mice with mutations in HR are known to have a higher susceptibility to ultraviolet radiation-induced tumorigenesis, suggesting that HR plays a crucial role in the epidermal UVB response. Using normal human keratinocytes (NHKs) and keratinocytes containing a mutation in HR, we found that HR is an early UVB response gene that negatively regulates NFκB mRNA expression. HR mutant keratinocytes have a dysregulated UVB response that includes increased proliferation and the aberrant activation of NFκB effector genes. Additionally, we show that another UVB response gene, TNFα, negatively regulates HR mRNA expression. TNFα-induced negative regulation of HR occurs through a direct interaction of the p65 subunit with a single NFκB-binding domain located in the HR promoter region. Therefore, we show for the first time that HR and NFκB participate in a positive feedback loop that can be initiated either by UVB or TNFα.