TRRAPING MYC: AIMING AT A MOVING TARGET

Edmond J. Feris and Michael D. Cole

Molecular Systems Biology, Geisel School of Medicine at Dartmouth College, Lebanon, USA

Abstract

Cancer has one of the highest mortality rates of any disease and the number of new cases is expected to rise by 70 percent over the next two decades. Our primary goal is to therapeutically target the oncogenic transcription factor, MYC, to stop tumor growth and cancer progression. The best-characterized MYC cofactor is TRRAP; the MYC-TRRAP interaction is critical for MYC's function in promoting cancer. The interaction between MYC and TRRAP occurs at a precise region in the MYC protein, called MYC Box 2 (MB2), which is central to the MYC transactivation domain (TAD). Although the TAD is disordered, our research tests the hypothesis that MB2 may acquire a defined structure when it is in complex with TRRAP. The MYC TAD, and particularly the MB2 motif, is highly unique and nearly invariant in evolution, suggesting that MB2 would be a good target for inhibiting MYC function. Our goal is to do just that: devise a strategy to therapeutically target MB2, the most sensitive and unique region of MYC.

Keywords: Cancer, MYC, drug discovery.