An extended Myc network contributes to glucose homeostasis in cancer and diabetes

Front Biosci (Landmark Ed). 2011 Jun 1;16:2206-23. doi: 10.2741/3848.

Abstract

The Myc network of transcription factors plays pleiotropic roles in normal and pathological cell function. The canonical Myc network controls how the essential nutrients glucose and glutamine are utilized inside cells. The Myc network carries out this function by upregulating glucose and glutamine transporters and key enzymes in the glycolytic or glutaminolytic pathways. The Myc network also coordinates cellular utilization of glucose and glutamine in biosynthetic pathways by directly regulating mitochondrial mass and activity. We present an argument for the existence of an "extended" Myc network comprised of two related transcription factors MondoA and ChREBP. Both MondoA and ChREBP sense glycolytic flux and are the principal regulators of glucose-dependent transcription in their respective tissues, skeletal muscle and liver. MondoA also senses glutaminolytic flux into the tricarboxylic acid cycle and appears to coordinate the utilization of glucose and glutamine by regulating expression of thioredoxin interacting protein. Current data suggest that the extended Myc network regulates the cellular response to changes in nutrient availability and may be altered in cancer and insulin resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arrestins / metabolism
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Carrier Proteins / metabolism
  • Cell Proliferation
  • Diabetes Mellitus / metabolism*
  • Glucose / metabolism*
  • Glutamine / metabolism
  • Homeostasis
  • Humans
  • Insulin Resistance / physiology
  • Metabolic Networks and Pathways
  • Mice
  • Models, Biological
  • Neoplasms / metabolism*
  • Nuclear Proteins / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Thioredoxins / metabolism
  • Transcription Factors / metabolism

Substances

  • Arrestins
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Carrier Proteins
  • Mlxipl protein, mouse
  • MondoA protein, mouse
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-myc
  • Transcription Factors
  • Txnip protein, mouse
  • Glutamine
  • Thioredoxins
  • Glucose