FoxO和ELP3调控赤拟谷盗Nrf2-Keap1信号通路及其靶标基因表达的分子机制

Nrf2-Keap1信号通路是细胞氧化应激反应中的关键通路。最近研究发现，该信号通路在调控果蝇蜕皮激素合成过程中也具有重要作用。目前国内外对昆虫Nrf2-Keap1信号通路的研究主要集中于其下游靶标基因的鉴定，尚无转录因子和翻译后修饰调控该信号通路的研究报道。叉头框转录因子FoxO和组蛋白乙酰转移酶ELP3在保护细胞抗氧化和蜕皮激素合成过程中也具有重要作用，提示这2个基因可能调控Nrf2-Keap1信号通路。本项目拟以赤拟谷盗为研究材料，应用定量PCR、RNA干扰、Western blot、荧光素酶报告基因和染色质免疫共沉淀等分子生物学技术，系统分析和比较赤拟谷盗CncC和Keap1基因对氧化应激和蜕皮激素合成相关基因表达的调控模式，探讨FoxO和ELP3基因对Nrf2-Keap1信号通路的调控机制。研究结果对于揭示昆虫Nrf2-Keap1信号通路作用的分子机制具有重要的科学意义。

Nrf2-Keap1 signaling pathway is the key pathway that mediates responses to oxidative stress, and recent studies have discovered that this pathway plays an important role in the regulation of ecdysone biosynthesis in Drosophila. Up to now, studies on insect Nrf2/Keap1 signaling pathway mainly forcus on the identification of its downstream target genes,and there is no reports on the role of transcription factor and posttranslational modification in the regulation of Nrf2-Keap1 signaling pathway at home and abroad.The fact that both Forkhead box class O (FoxO) transcription factor and histone acetyltransferase Elp3 play important roles in insect oxidative responses and ecdysone biosynthesis suggests that these two genes might regulat Nrf2-Keap1 signaling pathway. In this project, by using real-time quantitative PCR, RNA interference, Western blot, Luciferase report gene assays, Chromatin immunoprecipitation, and other molecular biology techniques, we will comparatively analyze the pattern of Tribolium castaneum CncC and Keap1 genes regulating the oxidative stress- and ecdysone biosynthesis-related genes, and investigate the mechanisms regulating Nrf2-Keap1 signaling pathway and its target gene expression by FoxO and ELP3. The results of this project will provide novel insights into the molecular mechanisms underlying the action of insect Nrf2-Keap1 signaling pathway.