Myc proto-oncogene protein-Max protein heterodimer (cMyc-Max) (cMyc-Max)

The cMyc-Max heterodimer is a transcription factor complex essential for the biological activity of the c-Myc oncoprotein [1, 2]. It is composed of the Myc proto-oncogene protein (c-Myc) and its obligate partner, the Max protein (Myc-associated factor X), both of which belong to the basic helix-loop-helix leucine zipper (bHLH-LZ) family [7, 15]. While c-Myc is an intrinsically disordered protein that cannot bind DNA effectively on its own, its heterodimerization with Max induces a conformational change that allows the complex to recognize and bind to E-box DNA sequences (5'-CACGTG-3') [15, 19]. This binding regulates the transcription of a vast network of genes involved in cell cycle progression, metabolism, protein synthesis, and apoptosis [11, 16]. In many human cancers, c-Myc is overexpressed or deregulated, making the cMyc-Max interaction a critical driver of tumor growth and a high-priority therapeutic target [1, 4]. Despite being historically labeled as undruggable due to its lack of defined binding pockets, several strategies have been developed to target the heterodimer, including small molecules like 10058-F4 and peptides like Omomyc that disrupt the protein-protein interaction or inhibit DNA binding [1, 3, 19]. Therapeutic inhibition of this complex aims to arrest the proliferation of MYC-dependent cancer cells, although potential toxicity in rapidly dividing normal tissues remains a clinical consideration [1, 20].

Other names

Myc-Maxc-Myc/Maxc-Myc-Max complexMyc-Max transcription factor

Inhibition of protein-protein heterodimerization between c-Myc and Max, stabilization of c-Myc monomers in an intrinsically disordered state, and/or abrogation of the heterodimer's ability to bind to E-box DNA sequences [1, 3, 19].