Structural and functional domains of the myb oncogene: requirements for nuclear transport, myeloid transformation, and colony formation.
The v-myb oncogene of avian myeloblastosis virus causes acute myelomonocytic leukemia in vivo and transforms only myeloid cells in vitro. Its product, p48v-myb, is a nuclear protein of unknown function. To determine structure-function relationships for this protein, we constructed a series of deletion mutants of v-myb, expressed them in retroviral vectors, and studied their biochemical and biological properties. We used these mutants to identify two separate domains of p48v-myb which had distinct roles in its accumulation in the cell nucleus. We showed that the viral sequences which normally encode both termini of p48v-myb were dispensible for transformation. In contrast, both copies of the highly conserved v-myb amino-terminal repeat were required for transformation. We also identified a carboxyl-terminal domain of p48v-myb which was required for the growth of v-myb-transformed myeloblasts in soft agar but not for morphological transformation.
Ibanez
C E
CE
Department of Pathology, University of California, San Diego, La Jolla 92093.
Lipsick
J S
JS
D000818:Animals; D001354:Avian Leukosis Virus / Q000235:genetics*; D009189:Avian Myeloblastosis Virus / Q000235:genetics*; D002451:Cell Compartmentation; D002455:Cell Division; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000503:physiopathology*; D002472:Cell Transformation, Viral; D003370:Coturnix; D004252:DNA Mutational Analysis; D004900:Erythroblasts / Q000166:cytology; D009687:Nuclear Proteins / Q000502:physiology*; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D009857:Oncogenes; D013329:Structure-Activity Relationship; D015017:Yolk Sac / Q000166:cytology
D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral