Protein truncation is required for the activation of the c-myb proto-oncogene.
The protein product of the v-myb oncogene of avian myeloblastosis virus, v-Myb, differs from its normal cellular counterpart, c-Myb, by (i) expression under the control of a strong viral long terminal repeat, (ii) truncation of both its amino and carboxyl termini, (iii) replacement of these termini by virally encoded residues, and (iv) substitution of 11 amino acid residues. We had previously shown that neither the virally encoded termini nor the amino acid substitutions are required for transformation by v-Myb. We have now constructed avian retroviruses that express full-length or singly truncated forms of c-Myb and have tested them for the transformation of chicken bone marrow cells. We conclude that truncation of either the amino or carboxyl terminus of c-Myb is sufficient for transformation. In contrast, the overexpression of full-length c-Myb does not result in transformation. We have also shown that the amino acid substitutions of v-Myb by themselves are not sufficient for the activation of c-Myb. Rather, the presence of either the normal amino or carboxyl terminus of c-Myb can suppress transformation when fused to v-Myb. Cells transformed by c-Myb proteins truncated at either their amino or carboxyl terminus appear to be granulated promyelocytes that express the Mim-1 protein. Cells transformed by a doubly truncated c-Myb protein are not granulated but do express the Mim-1 protein, in contrast to monoblasts transformed by v-Myb that neither contain granules nor express Mim-1. These results suggest that various alterations of c-Myb itself may determine the lineage of differentiating hematopoietic cells.
Grässer
F A
FA
Institut für Medizinische Mikrobiologie und Hygiene, Abteilung Virologie, Universitätskliniken des Saarlandes, Homburg, Germany.
Graf
T
T
Lipsick
J S
JS
D000818:Animals; D009189:Avian Myeloblastosis Virus / Q000235:genetics*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002645:Chickens; D002872:Chromosome Deletion; D004279:DNA, Viral / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors; D010957:Plasmids; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020598:Proto-Oncogene Proteins c-myb; D011519:Proto-Oncogenes; D011533:Proviruses / Q000235:genetics; D011784:Quail; D014161:Transduction, Genetic
D004279:DNA, Viral; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D011505:Protein-Tyrosine Kinases