Myc proto-oncogene protein (c-Myc) and N-myc proto-oncogene protein (MYCN) (MYC / MYCN)

Myc and N-Myc are members of the MYC family of basic helix-loop-helix leucine zipper (bHLH-LZ) transcription factors that function as master regulators of cellular processes [1, 3]. They form obligate heterodimers with the protein MAX to bind E-box sequences in the promoters of thousands of genes, thereby controlling approximately 15% of the human genome [3, 10, 11]. These targets include genes essential for cell cycle progression, metabolism, ribosome biogenesis, and apoptosis [1, 9, 14]. In many human cancers, MYC or MYCN are constitutively expressed or amplified, leading to uncontrolled proliferation, metabolic reprogramming, and poor clinical outcomes [1, 10, 12]. Historically, these proteins were considered "undruggable" due to their lack of a defined ligand-binding pocket and their intrinsically disordered nature [1, 11, 13]. However, modern therapeutic approaches are successfully targeting them through the disruption of the MYC-MAX interaction, the promotion of protein degradation via Aurora A inhibition, or the suppression of their transcription using BET inhibitors [8, 11, 17].

Other names

c-MycMYCbHLHe39MYCNN-mycbHLHe37NMYCv-myc avian myelocytomatosis viral oncogene homologv-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog

Inhibition of MYC-MAX dimerization, disruption of DNA binding at E-box sequences, promotion of ubiquitin-mediated protein degradation, and transcriptional repression of target genes