A single amino-acid substitution in the DNA-binding domain of the myb oncogene confers a thermolabile phenotype to E26-transformed myeloid cells.

A biologically active provirus of the ts 143 E26 mutant that is temperature-sensitive (ts) for myeloblast transformation was molecularly cloned. The predicted amino-acid sequence of the v-myb-encoded domain of the mutant P135gag-myb-ets protein displayed two single amino-acid changes, one of which was non-conservative when compared to the wild-type E26 v-myb sequence. This mutation, which substitutes a threonine residue (wild-type) for an arginine residue (mutant), is located within the amino-terminal part of v-myb in the DNA-binding domain at a position which is conserved between the c-myb genes of chicken, humans, mice and Drosophila. Introduction of this mutation into the genome of a wild-type E26 virus was sufficient to induce a ts phenotype similar to that obtained with the original ts 143 E26 virus.