Figure 2.

Model for competition between MNT-MAX and USF1 and MITF at a group of shared target genes involved in apoptosis and cell cycle arrest that are induced upon PI3K inhibition. Inhibition of PI3K signaling activates GSK3 and leads to the phosphorylation of USF1, MITF and FOXO transcription factors. Through mechanisms that remain unclear, phosphorylation by GSK3 is associated with the displacement of MNT-MAX with USF1 and MITF complexes at Ebox sites and the binding of FOXO factors at adjacent sites in proximal promoter regions of several genes induced by PI3K inhibition. This set of genes appears to not be regulated by MYC-MAX complexes. However, repression of these genes by MNT may cooperate with PI3K signaling and elevated MYC to promote proliferation and cell expansion by preventing apoptosis that might be otherwise sensitized due to the activities of high MYC.