Function and regulation of the transcription factors of the Myc/Max/Mad network.

The members of the Myc/Max/Mad network function as transcriptional regulators. Substantial evidence has been accumulated over the last years that support the model that Myc/Max/Mad proteins affect different aspects of cell behavior, including proliferation, differentiation, and apoptosis, by modulating distinct target genes. The unbalanced expression of these genes, e.g. in response to deregulated Myc expression, is most likely an important aspect of Myc's ability to stimulate tumor formation. Myc and Mad proteins affect target gene expression by recruiting chromatin remodeling activities. In particular Myc interacts with a SWI/SNF-like complex that may contain ATPase activity. In addition Myc binds to TRRAP complexes that possess histone acetyl transferase activity. Mad proteins, that antagonize Myc function, recruit an mSin3 repressor complex with histone deacetylase activity. Thus the antagonism of Myc and Mad proteins is explained at the molecular level by the recruitment of opposing chromatin remodeling activities.