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The scaffold protein JLP plays a key role in regulating ultraviolet B ‐induced apoptosis in mice
Author(s) -
Enkhtuya Radnaa,
Sato Tokiharu,
Wakasugi Mitsuo,
Tuvshintugs Baljinnyam,
Miyata Hirofumi,
Sakurai Takeshi,
Matsunaga Tsukasa,
Yoshioka Katsuji
Publication year - 2014
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12135
Subject(s) - biology , p38 mitogen activated protein kinases , apoptosis , microbiology and biotechnology , mapk/erk pathway , protein kinase a , keratinocyte , dna damage , signal transduction , scaffold protein , kinase , leucine zipper , cancer research , in vitro , transcription factor , biochemistry , dna , gene
The ultraviolet B ( UVB ) component of sunlight can cause severe damage to skin cells and even induce skin cancer. Growing evidence indicates that the UVB ‐induced signaling network is complex and involves diverse cellular processes. In this study, we investigated the role of c‐ J un NH 2 ‐terminal kinase‐associated leucine zipper protein ( JLP ), a scaffold protein for mitogen‐activated protein kinase ( MAPK ) signaling cascades, in UVB ‐induced apoptosis. We found that UVB ‐induced skin epidermal apoptosis was prevented in Jlp knockout ( KO ) as well as in keratinocyte‐specific Jlp KO mice. Analysis of the repair of UVB ‐induced DNA damage over time showed no evidence for the involvement of JLP in this process. In contrast, UVB ‐stimulated p38 MAPK activation in the skin was impaired in both Jlp KO and keratinocyte‐specific Jlp KO mice. Moreover, topical treatment of UVB ‐irradiated mouse skin with a p38 inhibitor significantly suppressed the epidermal apoptosis in wild‐type mice, but not in Jlp KO mice. Our findings suggest that JLP in skin basal keratinocytes plays an important role in UVB ‐induced apoptosis by modulating p38 MAPK signaling pathways. This is the first study to show a critical role for JLP in an in vivo response to environmental stimulation.