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

The cMyc-Max protein dimer is a heterodimeric transcription factor complex that serves as a master regulator of gene expression and is essential for the oncogenic activity of the c-Myc protein [1.1.1, 1.2.2]. c-Myc itself is an intrinsically disordered protein that lacks a stable structure until it dimerizes with its obligate partner, Max, through their respective basic helix-loop-helix leucine zipper (bHLH-ZIP) domains [1.2.1, 1.3.2]. This dimerization allows the complex to recognize and bind to specific DNA sequences known as E-boxes (5'-CACGTG-3'), where it recruits various co-activators to drive the transcription of genes involved in cell proliferation, metabolism, and cell growth [1.2.4, 1.3.3]. Because c-Myc is overexpressed or dysregulated in the majority of human cancers, the cMyc-Max dimer is a high-value therapeutic target [1.1.4, 1.2.3]. Although it was long considered "undruggable" due to the flat interface of the protein-protein interaction, recent advancements have led to the development of inhibitors such as the mini-protein Omomyc and various small molecules that disrupt the dimer or its DNA-binding capability [1.2.2, 1.5.2]. Targeting this complex aims to halt the uncontrolled proliferation of cancer cells and induce apoptosis, though challenges remain regarding potential toxicity in normal, rapidly dividing tissues [1.5.1].

Other names

c-Myc/Max heterodimerMYC/MAX complexMyc-Max dimerMYC-MAX

Inhibition of protein-protein interaction and DNA binding [1.1.1, 1.2.2]