UV INDUCED AND PERK MEDIATED SIGNALING PATHWAYS

紫外线诱导和 Perk 介导的信号通路

• 批准号: 6522628
• 负责人: Shiyong Wu
• 金额: $ 20.39万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6522628
• 关键词: BCL2 gene /protein; I kappa B beta; apoptosis; biological signal transduction; cysteine endopeptidases; flow cytometry; gel electrophoresis; genetic translation; intracellular transport; nuclear factor kappa beta; nucleic acid sequence; p53 gene /protein; phosphoproteins; phosphorylation; protein transport; tissue /cell culture; translation factor; ultraviolet radiation

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.

本提案的目的是研究PERK（类似于pkr的ER）的作用