The molecular role of Myc in growth and transformation: recent discoveries lead to new insights.

A major dilemma facing the Myc researcher is understanding how c-Myc regulation of gene transcription translates into the proliferative and oncogenic activities mediated by c-Myc protein. Indeed, much effort has focused on attempting to link c-Myc activation of gene transcription with both cell cycle progression and transformation mechanisms. Considerable progress has been made in recent years, with the identification of new Myc binding proteins as well as novel cellular targets of Myc-Max complexes. These discoveries have yielded more than a few surprises and challenged those working in the field to rethink traditional paradigms. It is now evident that c-Myc can also repress the transcription of specific genes, and Myc-mediated repression appears to be linked to Myc-dependent transformation. We summarize the evidence on Myc biological and molecular functions with regard to Myc-Max transcriptional regulation. In addition, we reevaluate current models of Myc transcriptional modulation in light of the discovery of new Myc binding partners and novel downstream target genes. Finally, we explore whether direct transactivation of cellular genes by Myc-Max heterodimers is sufficient for the growth-promoting and transforming activities of Myc or whether other molecular activities of Myc, such as Myc-mediated repression, may play a key role.