Figure 1.

MNT and its place in the MAX-MLX network of interacting proteins. Through its interaction with both MAX and MLX, MNT is positioned to compete with both MLXIP/MLXIP1 and MYC family proteins for interaction with MLX and MAX respectively, and for binding to shared target genes. Whereas MYC and MLXIP complexes promote transcription, MNT complexes repress transcription. Chromatin is depicted to indicate histone modifications and architecture that acts to promote transcription (green marks, relaxed conformation, MYC-MAX and MXLIP/1-MLX) or repress transcription (red marks, closed conformation, MNT-MAX, MNT-MLX). MXD-MAX, MXD-MLX and MGA-MAX complexes also repress transcription and may function in concert with MNT complexes to antagonize transcription by MYC and MLXIP complexes and fine-tune the expression of shared target genes. For MNT, its abundance can be downregulated by hypoxia and specifically through the inhibitory mRNA binding by miR-210 which is strongly induced by hypoxia. MNT can also be downregulated by the ubiquitin ligase E6AP. The effect of mitogenic signaling on MNT appears variable, with evidence that MNT is significantly increased in settings of sustained proliferation, but that in the setting of growth-factor-induced cell cycle entry, phosphorylation of MNT by ERK acting downstream in the MAPK pathway transiently interferes with MNT binding to SIN3 corepressors and its ability to antagonize transcription by MYC. See text for additional details.