MUTATIONS IN V-MYB ALTER THE DIFFERENTIATION OF MYELOMONOCYTIC CELLS TRANSFORMED BY THE ONCOGENE

被引:156
作者
INTRONA, M [1 ]
GOLAY, J [1 ]
FRAMPTON, J [1 ]
NAKANO, T [1 ]
NESS, SA [1 ]
GRAF, T [1 ]
机构
[1] EUROPEAN MOLEC BIOL LAB,DIFFERENTIAT PROGRAMME,W-6900 HEIDELBERG,GERMANY
关键词
D O I
10.1016/0092-8674(90)90424-D
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:1287 / 1297
页数:11
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