Tipping the MYC – MIZ 1 balance: targeting the HUWE 1 ubiquitin ligase selectively blocks MYC ‐activated genes

MYC family oncoproteins (MYC, N‐MYC and L‐MYC) function as basic helix‐loop‐helix‐leucine zipper ( bHLH ‐Zip) transcription factors that are activated (i.e., overexpressed) in well over half of all human malignancies (Boxer & Dang, [Boxer LM, 2001]; Beroukhim et al , [Beroukhim R, 2010]). In this issue of EMBO Molecular Medicine , Eilers and colleagues (Peter et al , [Peter S, 2014]) describe a novel approach to disable MYC, whereby inhibition of the ubiquitin ligase HUWE1 stabilizes MIZ1 and leads to the selective repression of MYC‐activated target genes.