The transforming activity of the chicken c-myc gene can be potentiated by mutations.

It was previously demonstrated that four different avian v-myc oncogenes harbor several point mutations. At least one of these leads to an amino acid substitution located in the proximity of position 61 in the second exon, whereas additional substitutions are found in exon 3. We have investigated whether these mutations affect the transforming activity of myc. By constructing avian retroviral genomes expressing hybrid gag-myc oncogenes, in which all or parts of the v-myc domains were replaced by corresponding parts of c-myc, we show here that a substitution of threonine 61 of c-myc for a methionine (as in v-mycmc29) significantly enhances the fibroblast transforming capacity of the recombinant oncogene. However, such a hybrid v/c-myc gene is still several fold less active than the v-mycmc29 oncogene. We have also expressed c-myc from subgenomic retroviral mRNAs: in these constructions the AUG of gag in the RNA leader sequence is in the same reading frame as that of c-myc, apparently leading to the production of a myc protein with 11 N-terminal amino acids encoded by gag and non-coding c-myc sequences. These myc proteins also transform chicken embryo fibroblasts, albeit with a lower efficiency than v-myc, again suggesting that mutations can increase the transforming capacity of myc.