MYC proto-oncogene (transcription factor) (MYC)

The MYC proto-oncogene encodes a transcription factor that drives cell growth, proliferation, and metabolism by forming heterodimers with MAX via its C-terminal basic helix-loop-helix leucine zipper (bHLHLZ) domain, binding to E-box DNA sequences (e.g., CACGTG) to regulate thousands of target genes. As part of the Proximal MYC Network (PMN), MYC integrates upstream signals to control cell cycle progression, differentiation, and apoptosis, while its antagonists like MXD1/MAX repress these functions. MYC is an intrinsically disordered protein (IDP) that folds upon binding MAX and DNA, with N-terminal transactivation domain (TAD) featuring Myc boxes for coactivator recruitment and a short half-life tuned by post-translational modifications (PTMs) such as phosphorylation and ubiquitination. Deregulation via overexpression or impaired degradation underlies most human cancers, correlating with tumor aggressiveness, rather than activating mutations typical of other oncogenes. Pharmacological targeting focuses on the MYC/MAX interface for inhibitor development, though paralog redundancy (MYCN, MYCL) poses challenges; experimental agents like Omomyc disrupt dimerization to suppress tumorigenesis.

Other names

c-MYCMYCN-MYC (MYCN)L-MYC (MYCL)

Disruption of MYC/MAX heterodimerization, Inhibition of protein-protein interactions at bHLHLZ domain, Blocking DNA binding to E-box sequences