Mutations in v-myb alter the differentiation of myelomonocytic cells transformed by the oncogene.
Chick myelomonocytic cells transformed by the v-myb oncogene-containing viruses E26 and AMV differ in that the former resemble myeloblasts and express the v-myb-regulated granulocyte-specific mim-1 gene, while the latter resemble monoblasts and are mim-1 negative. We constructed a series of AMV-E26 chimeras and localized the critical differences between these viruses to three point mutations within the second repeat of the v-myb DNA binding domain. These three positions are altered in the v-myb protein of AMV relative to the proteins encoded by c-myb or E26 v-myb. Back mutating AMV v-myb at any of these three sites restored the oncogene's ability to activate the mim-1 gene. Surprisingly, two of these changes led to the transformation, in vitro and in vivo, of cells having a promyelocyte-like phenotype. These results indicate that different forms of v-myb impose alternate phenotypes of differentiation on transformed myeloid cells, probably by regulating unique sets of differentiation-specific genes.
Introna
M
M
European Molecular Biology Laboratory, Heidelberg, Federal Republic of Germany.
Golay
J
J
Frampton
J
J
Nakano
T
T
Ness
S A
SA
Graf
T
T
D000818:Animals; D000911:Antibodies, Monoclonal; D009189:Avian Myeloblastosis Virus / Q000235:genetics*; D015152:Blotting, Northern; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D002645:Chickens; D006412:Hematopoietic Stem Cells / Q000166:cytology; D020626:Oncogene Proteins v-myb; D009857:Oncogenes; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D015183:Restriction Mapping; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*
D000911:Antibodies, Monoclonal; D020626:Oncogene Proteins v-myb; D012367:RNA, Viral; D015682:Retroviridae Proteins, Oncogenic; D011505:Protein-Tyrosine Kinases