To explorethe potential of incorporating novel residues into TFs, we selectedthe basic-helix–loop–helix leucine-zipper (bHLH-LZ)TF Myc–Max–Mad network, which plays a pivotal role inthe progression of human cancers., This networkcontrols the expression of approximately 15% of the human genome byforming dimeric complexes that selectively bind to promoter regionscontaining the enhancer box DNA sequence (5′-CACGTG-3′,E-box) to either activate or suppress gene expression. The Myc–Max–Mad network is involvedin key cellular processes such as cell proliferation, differentiation,and apoptosis. This evidence concerns the gene MAX and cancer.