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 r egulation of gene transcription translates into the proliferative and oncogenic activities mediated by c-Myc protein. Indeed, much effort ha s focused on attempting to link c-Myc activation of gene transcription with both cell cycle progression and transformation mechanisms. Consi derable progress has been made in recent years, with the identificatio n of new Myc binding proteins as well as novel cellular targets of Myc -Max complexes. These discoveries have yielded more than a few surpris es and challenged those working in the field to rethink traditional pa radigms, It is now evident that c-Myc can also repress the transcripti on of specific genes, and Myc-mediated repression appears to be linked to Myc-dependent transformation. We summarize the evidence on Myc bio logical and molecular functions with regard to]Myc-Max transcriptional regulation, In addition, we reevaluate current models of Myc transcri ptional modulation in light of the discovery of new Myc binding partne rs and novel downstream target genes, Finally, we explore whether dire ct transactivation of cellular genes by Myc-Max heterodimers is suffic ient for the growth-promoting and transforming activities of Myc or wh ether other molecular activities of Myc, such as Myc-mediated repressi on, may play a key role.