UV INDUCED AND PERK MEDIATED SIGNALING PATHWAYS

这项建议的目的是研究PERK(PKR样ER)的作用 激酶)在紫外线诱导的翻译抑制和细胞凋亡中的作用。以前的研究 已经证明紫外线可以诱导细胞凋亡，这可能在反应中起着重要作用 皮肤对紫外线的损害。拟议的研究将侧重于翻译 通过评估A的作用导致紫外线辐射的调节 新发现的翻译调节因子，在紫外线诱导的应激信号中的PERK 小路。这项拟议的研究将探讨紫外线诱导的机制 翻译调控及其在NFkB激活和细胞凋亡中的作用 具体目标1中提出的研究将确定详细的机制 蛋白质合成的抑制：紫外线诱导的蛋白质合成抑制 通过确定PERK激活和eIF2α磷酸化在 紫外线诱导的翻译调控通路。拟议的研究还将 确定导致紫外线翻译抑制的途径 紫外线诱导的PERK激活和eIF2α机制的研究 磷酸化。在目标2中提出的研究将调查 紫外线诱导NFkB活化中的PERK和翻译调控 证明紫外线诱导的IKB减少是否真的在 翻译级。这项拟议的研究还将确定 导致紫外线照射下的IKB减少，并证明PERK 调节NFkB的激活。目标3将确定PERK在紫外线诱导中的作用 通过系统地识别受调控的凋亡基因实现细胞凋亡 紫外线照射后的翻译水平。拟议的研究还将 研究与以下相关的上行和下行信号通路 紫外线诱导和PERK介导的细胞死亡。

The aim of this proposal is to study the role of PERK (PKR-like ER kinase) in UV-induced translational inhibition and apoptosis. Previous studies have shown that UV can induce apoptosis which may be important in the responses of skin to UV damage. The proposed study will focus on the translational regulation resulting in UV-radiation by evaluating the role of a newly-discovered translational regulator, PERK in UV induced stress signaling pathways. The proposed research will investigate the mechanism of UV-induced translational regulation and its role in NFkB activation and cell apoptosis. The research proposed in Specific Aim 1 will determine the detailed mechanism inhibition of protein synthesis for UV-induced inhibition of protein synthesis by determining the roles of PERK activation and EIF2alpha phosphorylation in UV-induced translational regulation pathways. The proposed research will also determine the pathways that lead to the translation inhibition upon UV irradiation and the mechanisms for UV-induced PERK activation and EIF2alpha phosphorylation. The research proposed in Aim 2 will investigate the roles of PERK and translational regulation in UV-induced NFkB activation by demonstrating whether UV UV-induced reduction in IkB is truly regulated at the translational level. The proposed research will also determine the pathway that leads to the reduction in IkB on UV irradiation and demonstrate whether PERK regulates NFkB activation. Aim 3 will determine the role of PERK in UV-induced apoptosis by systematically identifying apoptotic genes that are regulated at the translational level after UV irradiation. The proposed research will also investigate the upstream and downstream signaling pathways that are related to UV-induced and PERK-mediated cell death.