NF-κB is required for UV-induced JNK activation via induction of PKCδ
NF-κB is required for UV-induced JNK activation via induction of PKCδ
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DOI：
10.1016/j.molcel.2005.12.020
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发表时间：
2006-02-17
期刊：
影响因子：
16
通讯作者：
Lin, A
中科院分区：
文献类型：
--
作者：
Liu, J;Yang, D;Lin, A
紫外线通过激活下游效应分子，包括核因子-kappa B、JNK和半胱氨酸天冬氨酸氨基转移酶来发挥其生物学活性。紫外线诱导的细胞凋亡需要JNK的激活。目前尚不清楚核因子-kappa B和JNK之间是否会发生串扰来响应紫外线，如果是的话，它是如何影响紫外线杀灭的。在此，我们报道了核因子-kappaB促进紫外线诱导的JNK活化，从而促进紫外线诱导的细胞凋亡。紫外线对REIA/NF-kappa B缺失的小鼠胚胎成纤维细胞JNK活性的影响在静息细胞中，预先存在的核REIA已被募集到PKC Delta启动子上，并对其表达起着至关重要的作用。紫外线诱导的JNK的快速而强劲的激活需要PKC Delta，它通过其上游的激酶来增强JNK的磷酸化激活。REIA/NF-kappa B-PKC Delta-JNK通路在紫外线诱导的细胞凋亡中起关键作用，因为它诱导促凋亡的Fas配体的即时表达。因此，我们的结果表明，REIA/NF-kappa B通过PKC Delta正向调节UV诱导的JNK活化，并提供了一种促进UV诱导的细胞凋亡的机制。
Ultraviolet (UV) exerts its biological activities by activating downstream effectors, including NF-kappa B, JNK, and caspases. Activation of JNK is required for UV-induced apoptosis. It is unknown whether any crosstalk occurs between NF-kappa B and JNK in response to UV and, if so, how it affects UV killing. Here we report that NF-kappa B promotes UV-induced JNK activation, thereby contributing to UV-induced apoptosis. UV-induced JNK activation is impaired in ReIA/NF-kappa B null murine embryonic fibroblasts. In resting cells, the preexisting nuclear ReIA has already been recruited to PKC delta promoter and is essential for its expression. UV-induced rapid and robust activation of JNK requires PKC delta, which augments JNK phosphorylation-activation by its upstream kinases. The ReIA/NF-kappa B-PKC delta-JNK pathway is critical for UV-induced apoptosis, as it induces the immediate expression of the proapoptotic Fas ligand. Thus, our results demonstrate that ReIA/NF-kappa B via PKC delta positively regulates UV-induced JNK activation and provide a mechanism by which NF-kappa B promotes UV-induced apoptosis.