Selective repression of myoD transcription by v-Myc prevents terminal differentiation of quail embryo myoblasts transformed by the MC29 strain of avian myelocytomatosis virus.

We have investigated the mechanism by which expression of the v-myc oncogene interferes with the competence of primary quail myoblasts to undergo terminal differentiation. Previous studies have established that quail myoblasts transformed by myc oncogenes are severely impaired in the accumulation of mRNAs encoding the myogenic transcription factors Myf-5, MyoD and Myogenin. However, the mechanism responsible for such a repression remains largely unknown.

Omomyc, a potential Myc dominant negative, enhances Myc-induced apoptosis.

The Myc basic helix-loop-helix zipper domain determines dimerization with Max and binding to the DNA E-box, both of which play a critical role in Myc regulation of growth, proliferation, tumorigenesis, and apoptosis. The mutant basic helix-loop-helix zipper domain, Omomyc, dimerizes with Myc, sequestering it in complexes unable to bind the E-box, and so acting as a potential dominant negative. Consistent with this, Omomyc reverses Myc-induced cytoskeletal disorganization in C2C12 myoblasts.