MYC Cofactors: Molecular Switches Controlling Diverse Biological Outcomes

The transcription factor MYC has fundamental roles in proliferation, apoptosis, tumorigene-sis, and stemcell pluripotency.Over the last 30years extensive informationhasbeengathered on the numerous cofactors that interact with MYC and the target genes that are regulated by MYC as a means of understanding the molecular mechanisms controlling its diverse roles. Despite significant advances and perhaps because the amount of information learned about MYC is overwhelming, therehasbeen little consensuson themolecular functionsofMYC that mediate its critical biological roles. In this perspective, themajorMYCcofactors that regulate the various transcriptional activities of MYC, including canonical and noncanonical trans-activation and transcriptional repression, will be reviewed and a model of how these tran-scriptional mechanisms control MYC-mediated proliferation, apoptosis, and tumorigenesis will be presented. The basis of the model is that a variety of cofactors form dynamic MYC transcriptional complexes that can switch the molecular and biological functions of MYC to yield a diverse range of outcomes in a cell-type- and context-dependent fashion. The c-Myc protein (MYC) plays a critical rolein cellular proliferation, cell size, differen-tiation, stem cell self-renewal, and apoptosis