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

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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.