 NYC family-on-coproteins NYC, N-mike and L-mike function as basic helix-loop helix-leusine zippa, BHLH-zip, transcription factors that are activated, overexpressed, in well over half of all human malignancies, boxer and dang, beruchim et al. In this issue of EMBO molecular medicine, Eylers and colleagues, Peter et al, describe a novel approach to disable NYC, whereby inhibition of the ubiquitin ligase-HU1 stabilizes MIZ1 and leads to the selective repression of micactivated target genes. This article was offered by Franz X-Shorgh and John L. Cleveland.