Figure 3.

The Myc and Mlx Networks cross-talk to modulate TXNIP and glycolysis. The G6P-mediated cytoplasmic → nuclear transport of MondoA-Mlx heterodimers (and probably ChREBP-Mlx heterodimers as well) facilitates their binding to tandem ChoREs in the TXNIP gene’s promoter and up-regulates its expression [30,32,85,88]. Among the functions of TXNIP is to enhance endocytosis of the Glut1 and Glut4 glucose receptors encoded by SLCA1 and SLC2A4 genes [86,89]. Myc down-regulates TXNIP in part by displacing MondoA/ChREBP-Mlx heterodimers at ChoREs [87]. Myc also directly facilitates glucose uptake via binding to E boxes in the proximal promoters of the SLC2A1 and SLC2A4 genes and further drives glycolysis by a similar induction of the H2K gene, whose encoded protein, hexokinase 2, is one of the rate-limiting enzymes of glycolysis [52,65]. Genes that are direct targets for members of the Myc and/or Mlx Networks are shown in red.