Mechanism of regulation of c-JUN activity via its phosphorylation by the JNK kinase in cancer

癌症中 JNK 激酶磷酸化 c-JUN 活性的调节机制

• 批准号: 2749627
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2749627
• 关键词: Mechanism; regulation; JUN; activity; via

The project will study 1.the mechanism by which CHD4 terminates c-JUN/JNK signalling and the role of this novel interaction in colon cancer growth, and 2. the effect of the CHD4 mutations on the regulation of c-JUN activity and identify c-JUN target genes that are controlled by the c-JUN/CHD4 axis, and deregulated by CHD4 cancer mutations.This research will for the first time provide a mechanistic explanation for the high c-JUN expression and activity in cancer. Protein effectors of c-JUN/CHD4 upregulated in colon cancer patients bearing CHD4 mutations, may identify cancer vulnerabilities that can be therapeutically exploited. This is a multidisciplinary research project combining in vitro biochemical with in vivo cellular biology techniques and in silico mathematical modelling.

该项目将研究1。1 . CHD4终止c-JUN/JNK信号的机制以及这种新的相互作用在结肠癌生长中的作用；研究CHD4突变对c-JUN活性调控的影响，并鉴定受c-JUN/CHD4轴调控、CHD4癌突变解除调控的c-JUN靶基因。本研究将首次为c-JUN在癌症中的高表达和高活性提供机制解释。c-JUN/CHD4蛋白效应器在携带CHD4突变的结肠癌患者中上调，可能识别出可用于治疗的癌症脆弱性。这是一个多学科的研究项目，结合了体外生化与体内细胞生物学技术和计算机数学建模。