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Serpin squamous cell carcinoma antigen inhibits UV-induced apoptosis via suppression of c-JUN NH(2)-terminal kinase
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-...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063756/ https://www.ncbi.nlm.nih.gov/pubmed/16549498 http://dx.doi.org/10.1083/jcb.200508064 |
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author | Katagiri, Chika Nakanishi, Jotaro Kadoya, Kuniko Hibino, Toshihiko |
author_facet | Katagiri, Chika Nakanishi, Jotaro Kadoya, Kuniko Hibino, Toshihiko |
author_sort | Katagiri, Chika |
collection | PubMed |
description | 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 NH(2)-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. |
format | Text |
id | pubmed-2063756 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-20637562007-11-29 Serpin squamous cell carcinoma antigen inhibits UV-induced apoptosis via suppression of c-JUN NH(2)-terminal kinase Katagiri, Chika Nakanishi, Jotaro Kadoya, Kuniko Hibino, Toshihiko J Cell Biol Research Articles 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 NH(2)-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. The Rockefeller University Press 2006-03-27 /pmc/articles/PMC2063756/ /pubmed/16549498 http://dx.doi.org/10.1083/jcb.200508064 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Katagiri, Chika Nakanishi, Jotaro Kadoya, Kuniko Hibino, Toshihiko Serpin squamous cell carcinoma antigen inhibits UV-induced apoptosis via suppression of c-JUN NH(2)-terminal kinase |
title | Serpin squamous cell carcinoma antigen inhibits UV-induced apoptosis via suppression of c-JUN NH(2)-terminal kinase |
title_full | Serpin squamous cell carcinoma antigen inhibits UV-induced apoptosis via suppression of c-JUN NH(2)-terminal kinase |
title_fullStr | Serpin squamous cell carcinoma antigen inhibits UV-induced apoptosis via suppression of c-JUN NH(2)-terminal kinase |
title_full_unstemmed | Serpin squamous cell carcinoma antigen inhibits UV-induced apoptosis via suppression of c-JUN NH(2)-terminal kinase |
title_short | Serpin squamous cell carcinoma antigen inhibits UV-induced apoptosis via suppression of c-JUN NH(2)-terminal kinase |
title_sort | serpin squamous cell carcinoma antigen inhibits uv-induced apoptosis via suppression of c-jun nh(2)-terminal kinase |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063756/ https://www.ncbi.nlm.nih.gov/pubmed/16549498 http://dx.doi.org/10.1083/jcb.200508064 |
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