Minimal truncation of the c-myb gene product in rapid-onset B-cell lymphoma.
Oncogenic activation of c-myb by insertional mutagenesis has been implicated in rapid-onset B-cell lymphomas induced by the nonacute avian leukosis virus EU-8. In these tumors, proviruses are integrated either upstream of the c-myb coding region or within the first intron of c-myb. Tumors with either type of integration contained identical chimeric mRNAs in which the viral 5' splice site was juxtaposed to the 3' splice site of c-myb exon 2 and myb exon 1 was eliminated. Both classes of integrations generated truncated Myb proteins that were indistinguishable by Western analysis. In contrast to most other examples of c-myb activation, the truncation consisted of only 20 N-terminal amino acids and did not disrupt either the DNA binding domain near the N terminus or the negative regulatory domain near the C terminus of Myb. The significance of the 20-amino-acid Myb truncation to tumorigenesis was tested by infection of chicken embryos with retroviral vectors expressing different myb gene products. While virus expressing either wild-type c-myb or c-myb mutated at the N-terminal casein kinase II sites was only weakly oncogenic at 10 weeks, the minimally truncated myb virus induced a high incidence of rapid-onset tumors, including B-cell lymphomas, sarcomas, and adenocarcinomas.
Jiang
W
W
Laboratory of Molecular Genetics and Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Kanter
M R
MR
Dunkel
I
I
Ramsay
R G
RG
Beemon
K L
KL
Hayward
W S
WS
D017398:Alternative Splicing; D000818:Animals; D001354:Avian Leukosis Virus / Q000235:genetics / Q000502:physiology*; D047390:Casein Kinase II; D002645:Chickens; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005822:Genetic Vectors; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D020598:Proto-Oncogene Proteins c-myb; D011533:Proviruses; D011995:Recombination, Genetic; D012190:Retroviridae; D017384:Sequence Deletion; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D016662:Virus Integration
D018076:DNA, Complementary; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases