High-throughput, quantitative measurements reveal the biophysical mechanisms by which transcription factor mutations drive disease.

Abstract

The Myc-Max-Mad triad of basic helix-loop-helix (bHLH) human transcription factors (TFs) regulate cell cycle progression. Mutations to or overexpression of these TFs drive aberrant expression of a large fraction of the genome in over 40% of cancers. Understanding the biophysical mechanisms by which alterations in these TF complexes—both the transcriptionally inactive Max-Max homodimer and the strongly activating Myc-Max heterodimer—disrupt function could therefore reveal new therapeutic approaches to restore normal gene expression and prevent proliferation.