A major human oncoprotein

The term “MYC” refers to a family of three related oncogenes that are broadly over-expressed in cancer and contribute to an estimated 100,000 cancer deaths annually in the United States alone. MYC proteins function as transcriptional regulators, controlling the expression of thousands of genes linked to cell growth, proliferation, metabolism, and genomic instability. MYC proteins are highly-validated but challenging drug targets for cancer therapy. Our work seeks to expose basic mechanisms of MYC action that can lead to new strategies to target MYC in the clinic. Our research has two specific areas of focus:

The enigmatic MYC “central portion”. MYC family members are among the most intensely studies proteins in human history. Structure-function analyses have delineated critical activation and DNA-binding domains in the two extremes of MYC, but the central portion that lies between these domains is largely uncharacterized. We believe that understanding the function of this region can reveal novel MYC interaction partners and mechanisms of action that can be exploited to block MYC function in cancer cells.

The WDR5–MYC nexus. Our interest in the MYC central portion led to identification of the WD40-repeat-containing protein WDR5 as a direct MYC binding partner. We hypothesize that WDR5 facilitates the recruitment of MYC to chromatin. We also hypothesize that properties of the MYC–WDR5 interface make it a viable point for discovery of small molecule inhibitors of MYC activity. We want to know how MYC and WDR5 work together, what other proteins are involved, and how understanding of the MYC–WDR5 nexus can inform anti-cancer therapies.


© Bill Tansey 2021