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 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 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.

Stress signaler p38 mitogen-activated kinase activation: a cause for concern?

“…After treatments, the tissues were transferred to Tissue-Tek optimal cutting temperature (O.C.T, Sakura Finetek, Tokyo, Japan) compound to snap freeze for immunohistology. IHC was done as previously described [ 32 , 34 ]. Briefly, 10 µm tissue sections were air-dried on the slide glasses (Matsunami Glass, Osaka, Japan) for 40 min at RT, then washed with tris-buffered saline with 0.1% Tween20 (1× TBST) for 10 min.…”

Development of a mouse model of ascending infection and preterm birth

“…Mice were then sacrificed at 6, 24, or 48 hr after bacterial administration. Frozen sections of reproductive tissues (cervix, uterus, placenta, fetal membrane, and pups) were subjected to microscopic analysis for the CFSE signal as described previously [ 60 ]. Briefly, the collected tissues were fixed in 4% PFA overnight at 4°C, then incubated in 30% sucrose for additional 24 hr at 4°C for cryoprotection.…”

Overexpression of JNK‐associated leucine zipper protein induces chromosomal instability through interaction with dynein light intermediate chain 1

“…The c‐Jun N‐terminal kinase (JNK)‐associated leucine zipper protein (JLP), also known as SPAG9 or JIP4, was first identified as a scaffold protein of the JNK and p38 MAPK signaling pathways (Kelkar et al, 2005; Lee et al, 2002). JLP‐JNK/p38 signaling plays a role in myogenesis (Takaesu et al, 2006), neurite outgrowth (Xu et al, 2010), and cell death (Boldbaatar et al, 2020; Enkhtuya et al, 2014; Li et al, 2018). Apart from scaffolding functions in MAPK pathways, JLP is considered to be involved in a variety of cellular processes, including cytokinesis and lysosome positioning (Kumar et al, 2022; Montagnac et al, 2009; Suzuki et al, 2020; Tuvshintugs et al, 2014; Willett et al, 2017), through its interacting proteins, like kinesin‐1 and cytoplasmic dynein 1 (hereafter, referred to as dynein).…”

“…JLP and its paralog JNK/stress‐activated protein kinase‐associated protein 1 (JSAP1) (Ito et al, 1999), also known as JIP3 (Kelkar et al, 2000), share similar domain structures, including JNK/p38 MAPK‐binding domain (MBD) and kinesin‐1 heavy chain (KHC)‐binding domains (KBD) (Ito et al, 2000; Sun et al, 2011), suggesting their functional redundancy. Additionally, gene knockout studies in mice have reported that JLP and JSAP1 have overlapping, as well as distinct functions: Jlp knockout mice are viable, grow normally, and exhibit male subfertility (Enkhtuya et al, 2014; Iwanaga et al, 2008), but Jsap1 knockout mice die just after birth due to respiratory failure (Ha et al, 2005; Kelkar et al, 2003). In contrast, studies with conditional knockout mice have revealed that although both Jlp and Jsap1 are involved in postnatal brain development (Sato, Ishikawa, Mochizuki, et al, 2015) and Purkinje cell survival (Sato, Ishikawa, Yoshihara, et al, 2015) in mice, their roles are redundant.…”