Myc, mondo, and metabolism

The Myc family of proto-oncogenes plays a central role in tumorigenesis, yet identifying the specific transcriptional targets required for its oncogenic function remains a challenge. Given Myc's broad role in transcriptional regulation, it seems unlikely that there exists one or even a small set of Myc effectors strictly required for transformation. Over the last decade or so, it has become clear that Myc can drive several metabolic pathways associated with cell growth. There is compelling evidence that Myc regulates these pathways directly and that their regulation is not an epiphenomenon. As such, for understanding Myc's pleiotropic role in cell growth, cell division, and cell death, it may be fruitful to focus more broadly on Myc-regulated pathways than on specific targets. Myc was first shown to regulate glycolysis, but it is now clear that Myc regulates many biosynthetic pathways required for cell growth and division. A related family of transcriptional regulators, the Mondo family, has recently been discovered that may interact with members of the Myc family to control cell growth. The Mondo family is a key sensor of intracellular bioenergetic charge, and one function appears to be in controlling the availability and utilization of intracellular glucose. Here we focus on the metabolic pathways regulated by Myc and Mondo and speculate on the largely unexplored question of their cooperation in controlling cancer cell metabolism.