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Published online 20 March 2006. doi:10.1083/jcb.200508064
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 172, Number 7, 983-990
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 Serpin squamous cell carcinoma antigen inhibits UV-induced apoptosis via suppression of c-JUN NH2-terminal kinase

Chika Katagiri, Jotaro Nakanishi, Kuniko Kadoya, and Toshihiko Hibino

Shiseido Life Science Research Center, Kanazawa-ku, Yokohama 236-8643, Japan

Correspondence to Toshiko Hibino: toshihiko.hibino{at}to.shiseido.co.jp


Abstract
Protection from ultraviolet (UV) irradiation is a fundamental issue for living organisms. Although melanin's critical role in the protection of basal keratinocytes is well understood, other factors remain essentially unknown. We demonstrate that up-regulation of squamous cell carcinoma antigen-1 (SCCA1) suppresses c-Jun NH2-terminal kinase-1 (JNK1) and thus blocks UV-induced keratinocyte apoptosis. We found that serpin SCCA1 is markedly elevated in the top layers of sun-exposed or UV-irradiated epidermis. UV-induced apoptosis was significantly decreased when SCCA was overexpressed in 3T3/J2 cells. It was significantly increased when SCCA was down-regulated with small interfering RNA in HaCaT keratinocytes. A search for SCCA-interacting molecules showed specific binding with phosphorylated JNK. Interestingly, SCCA1 specifically suppressed the kinase activity of JNK1. Upon exposure of keratinocytes to UV, SCCA1 was bound to JNK1 and transferred to the nucleus. Involucrin promoter–driven SCCA1 transgenic mice showed remarkable resistance against UV irradiation. These findings reveal an unexpected serpin function and define a novel UV protection mechanism in human skin.

K. Kadoya's present address is The Burnham Institute, La Jolla, CA 92037.

Abbreviations used in this paper: JIP1, JNK-interacting protein-1; JNK, c-Jun NH2-terminal kinase; MAPKAPK2, MAPK-activated protein kinase-2; NHK, neonatal human keratinocytes; SCCA, squamous cell carcinoma antigen; SAPK, stress-activated protein kinase; siRNA, small interfering RNA; siSCCA, small interfering SCCA.


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