UV INDUCED AND PERK MEDIATED SIGNALING PATHWAYS

本研究的目的是研究PERK（PKR-like ER）在乳腺癌中的作用， 激酶）在UV诱导的翻译抑制和细胞凋亡中的作用。以前的研究 已经表明，紫外线可以诱导细胞凋亡，这可能是重要的反应， 皮肤受到紫外线伤害。该研究将集中在翻译 调节导致紫外线辐射的作用进行评估， 新发现的翻译调节因子PERK在紫外线诱导的应激信号中的作用 途径。该研究将探讨紫外线诱导的机制， 翻译调控及其在NF κ B活化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 UV诱导的蛋白质合成抑制 通过确定PERK激活和EIF 2 α磷酸化在 UV诱导的翻译调节途径。拟议的研究还将 确定导致UV翻译抑制的途径 辐射和紫外线诱导的PERK激活和EIF 2 α的机制 磷酸化目标2中提出的研究将调查 PERK和翻译调节在UV诱导的NF κ B活化中的作用 证明UV UV诱导的IkB减少是否真的在 翻译水平。拟议的研究还将确定 导致UV照射下IkB的降低，并证明PERK 调节NFkB活化。目的3将确定PERK在UV诱导的细胞凋亡中的作用。 通过系统地鉴定凋亡基因， UV照射后的平移水平。拟议的研究还将 研究上游和下游信号通路， UV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.