Transformation by v-myb correlates with trans-activation of gene expression.
The v-myb oncogene of avian myeloblastosis virus causes acute myelomonocytic leukemia in chickens and transforms avian myeloid cells in vitro. Its protein product p48v-myb is a nuclear, sequence-specific, DNA-binding protein which activates gene expression in transient DNA transfection studies. To investigate the relationship between transformation and trans-activation by v-myb, we constructed 15 in-frame linker insertion mutants. The 12 mutants which transformed myeloid cells also trans-activated gene expression, whereas the 3 mutants which did not transform also did not trans-activate. This implies that trans-activation is required for transformation by v-myb. One of the transformation-defective mutants localized to the cell nucleus but failed to bind DNA. The other two transformation-defective mutants localized to the cell nucleus and bound DNA but nevertheless failed to trans-activate. These latter mutants define two distinct domains of p48v-myb which control trans-activation by DNA-bound protein, one within the amino-terminal DNA-binding domain itself and one in a carboxyl-terminal domain which is not required for DNA binding.
Lane
T
T
Department of Pathology, University of California, San Diego, La Jolla 92093.
Ibanez
C
C
Garcia
A
A
Graf
T
T
Lipsick
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001354:Avian Leukosis Virus / Q000235:genetics*; D009189:Avian Myeloblastosis Virus / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004251:DNA Transposable Elements; D015972:Gene Expression Regulation, Neoplastic; D008969:Molecular Sequence Data; D009154:Mutation; D020626:Oncogene Proteins v-myb; D009857:Oncogenes; D010957:Plasmids; D011784:Quail; D015183:Restriction Mapping; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D015533:Transcriptional Activation
D004251:DNA Transposable Elements; D020626:Oncogene Proteins v-myb; D015682:Retroviridae Proteins, Oncogenic