BACKGROUND: c-Jun N-terminal kinase (JNK) plays a critical role in UV-induced apoptotic cell death. Although three isoforms are known in mammals, physiological roles of each isoform are still obscure. Furthermore, our recent findings show that serpin squamous cell carcinoma antigen (SCCA1) binds to JNK. OBJECTIVE: To determine which isoform is responsible for the UV signal transduction in human epidermis and whether SCCA1 is capable to regulate kinase activity of a specific isoform. METHODS: Immunohistochemical localization of each JNK isoform was investigated after UV irradiation in vivo and in vitro. Effect of recombinant SCCA1 on JNK kinase activity was also analyzed. RESULTS: Immunostaining for JNK1, 2 and 3 demonstrated marked elevation of JNK1 in spinous to granular cells of UV-irradiated skin, whereas they were expressed weakly in upper epidermis of the sun-protected, buttock skin. In cultured keratinocytes, only JNK1 is translocated into nucleus after UV irradiation. JNK2, which localized in the cytoplasm, or JNK3, which was confined in nucleus, remained in the same compartment after UV irradiation. We confirmed that only JNK1 mRNA was up-regulated after UV irradiation in cultured keratinocytes. In addition, recombinant SCCA1 suppressed kinase activity of JNK1 but did not affect JNK2 or JNK3 kinase activity. CONCLUSION: JNK1 is associated with UV signal transduction in human epidermis and SCCA1 is a suppressor of this process.
BACKGROUND:c-Jun N-terminal kinase (JNK) plays a critical role in UV-induced apoptotic cell death. Although three isoforms are known in mammals, physiological roles of each isoform are still obscure. Furthermore, our recent findings show that serpin squamous cell carcinoma antigen (SCCA1) binds to JNK. OBJECTIVE: To determine which isoform is responsible for the UV signal transduction in human epidermis and whether SCCA1 is capable to regulate kinase activity of a specific isoform. METHODS: Immunohistochemical localization of each JNK isoform was investigated after UV irradiation in vivo and in vitro. Effect of recombinant SCCA1 on JNK kinase activity was also analyzed. RESULTS: Immunostaining for JNK1, 2 and 3 demonstrated marked elevation of JNK1 in spinous to granular cells of UV-irradiated skin, whereas they were expressed weakly in upper epidermis of the sun-protected, buttock skin. In cultured keratinocytes, only JNK1 is translocated into nucleus after UV irradiation. JNK2, which localized in the cytoplasm, or JNK3, which was confined in nucleus, remained in the same compartment after UV irradiation. We confirmed that only JNK1 mRNA was up-regulated after UV irradiation in cultured keratinocytes. In addition, recombinant SCCA1 suppressed kinase activity of JNK1 but did not affect JNK2 or JNK3 kinase activity. CONCLUSION:JNK1 is associated with UV signal transduction in human epidermis and SCCA1 is a suppressor of this process.
Authors: Hengning Ke; Rebecca Harris; Jonathan L Coloff; Jane Y Jin; Benjamin Leshin; Paula Miliani de Marval; Shiying Tao; Jeffrey C Rathmell; Russell P Hall; Jennifer Y Zhang Journal: Cancer Res Date: 2010-03-30 Impact factor: 12.701