Transforming ability of Gag-Myc fusion proteins correlates with Gag-Myc protein stability and transcriptional repression.

Avian retroviruses that have transduced c-myc are useful tools to study the conditions necessary for cellular transformation. FH3, one such retrovirus which encodes a Gag-Myc fusion protein, is not transforming in quail embryonic fibroblasts, but a late variant of FH3 that arose after passaging FH3-infected cells is transforming. Mutational analysis of FH3 revealed that the presence of a portion of the retroviral protease in FH3 inhibited transformation and that this inhibition was transferable to a more highly transforming retrovirus, MC29. Transforming and non-transforming FH3-derived and MC29-derived Gag-Myc proteins were used to further explore characteristics of Myc necessary for transformation. Gag-Myc proteins which were transforming were found to be the most stable in the cell. To distinguish whether transactivation and/or repression is correlated to transformation, the various Gag-Myc fusion proteins were tested for their ability to activate or repress c-Myc targets. Results indicated that a correlation exists between transforming Gag-Myc proteins and their ability to repress, whereas all Gag-Myc proteins could transactivate, regardless of their ability to transform. Taken together, these results suggest that protein stabilization of Myc and repression of target genes by Myc are important for cellular transformation.