Myc proto-oncogene protein (MYC) (MYC)

The Myc proto-oncogene protein (MYC) is a master transcription factor that orchestrates the MYC transcriptional program, a vast network regulating approximately 15% of all human genes (Dang, 2012, PMID: 22464326). It functions by forming a heterodimer with its partner MAX, which then binds to E-box sequences in the promoters of target genes involved in cell cycle progression, metabolism, and ribosome biogenesis (Kress et al., 2015, PMID: 25707818). In many human cancers, MYC is constitutively overexpressed due to gene amplification, translocations, or oncogenic signaling, driving the hallmarks of cancer such as uncontrolled proliferation and metabolic reprogramming (Gabay et al., 2014, PMID: 24907528). Historically considered "undruggable" due to its lack of a defined small-molecule binding pocket and its intrinsically disordered nature, MYC is now being targeted through indirect methods such as BET bromodomain inhibitors that suppress its transcription, or direct methods like the mini-protein Omomyc that disrupts MYC-MAX dimerization (Duffy et al., 2021, PMID: 33033131). Successful modulation of the MYC transcriptional program holds significant therapeutic potential across a wide range of malignancies, although managing the potential toxicity to normal, rapidly proliferating tissues remains a critical challenge (Llombart & Mansour, 2022, PMID: 35418193).

Other names

c-MycMYCCbHLHe39Proto-oncogene c-MycTranscription factor p64Class E basic helix-loop-helix protein 39MRTL

Inhibition of MYC gene transcription via BET bromodomain inhibition, disruption of MYC-MAX heterodimerization to prevent DNA binding, and induction of MYC protein degradation through proteasomal pathways.