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 UVBinduced
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.