title: The scaffold protein JLP plays a key role in regulating ultraviolet B-induced apoptosis in mice.
abstract: 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-Jun NH2 -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.
authors: Division of Molecular Cell Signaling, Cancer Research Institute, Kanazawa University, Kanazawa, 920-1192, Japan.
authors: Radnaa
authors: R
authors: Enkhtuya
authors: Tokiharu
authors: T
authors: Sato
authors: Mitsuo
authors: M
authors: Wakasugi
authors: Baljinnyam
authors: B
authors: Tuvshintugs
authors: Hirofumi
authors: H
authors: Miyata
authors: Takeshi
authors: T
authors: Sakurai
authors: Tsukasa
authors: T
authors: Matsunaga
authors: Katsuji
authors: K
authors: Yoshioka
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D053938:DNA Fragmentation; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D007093:Imidazoles / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D020935:MAP Kinase Signaling System; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011725:Pyridines / Q000494:pharmacology; D014466:Ultraviolet Rays / Q000009:adverse effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007093:Imidazoles; D011725:Pyridines; C468928:Spag9 protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580