MULTIPLE PHENOTYPES ASSOCIATED WITH MYC-INDUCED TRANSFORMATION OF CHICK-EMBRYO FIBROBLASTS CAN BE DISSOCIATED BY A BASIC REGION MUTATION

Chimaeric alleles were constructed to assay the biological functions o f an N-terminal deletion and C-terminal mutations which were found in a naturally occurring mutant of feline vMyc, T17. The mutant alleles w ere assayed for their ability to transform chick embryo fibroblasts in vitro by a number of criteria, namely the ability to induce morpholog ical transformation, an accelerated growth rate and growth in soft aga r, Feline cMyc could transform the avian cells, whilst T17 vMyc could not, and the N-terminal deletion was responsible for conferring the pr imary transformation defect on the mutant protein. The C-terminal muta tions which consist of a point mutation adjacent to the nuclear locali sation signal and a point mutation/amino acid insertion within the bas ic region (BR) could, however, dissociate the Myc-induced parameters o f transformation, This effect was a specific function of the BR mutati on alone, and the mutation could be transferred into avian cMyc with c omparable biological consequences. The BR mutation did not disrupt the sequence specific DNA binding activity of the protein in vivo, despit e exerting a biological effect. These data suggest a novel phenotype w here the mutation may affect a subset of Myc-regulated genes through a ltered DNA binding specificity or protein-protein interactions.