Structure and mechanism of activation of the myb oncogene.
The results summarized in this review show that the normal chicken myb gene codes for a protein of 77 kd which appears to play an important role in the control and/or differentiation of hematopoietic cells of myeloid and T lymphoid series. The activation of this gene has been observed in chicken and murine systems. In the avian system, this has been achieved by transduction of the myb oncogene into a retrovirus. Such a transduction resulted in the deletion of coding sequences from both the 5' and 3' ends of the gene. Initiation and terminator codons in helper viral sequences have been substituted for the analogous sequences in the proto-oncogene. Deletion of similar stretches of sequence in both the viruses suggested the possibility that these deletions may play an important role in the activation of this gene. The availability of the murine model system allowed us to examine this question further. In the ABPL tumor system, the activation of the myb locus occurred as a result of viral integration in a region immediately upstream to the v-myb related sequences. In NSF-60 cell line, the activation is due to the viral integration toward the 3' end of the gene. In both cases the viral integration results in the synthesis of aberrant mRNAs that have suffered deletions similar to those observed in the avian system. In all instances this results in the synthesis of truncated proteins which appear to mediate the transforming function. The availability of chicken and mouse c-myb cDNA clones makes it possible to test this hypothesis directly by construction of retroviruses containing various deletion mutations.
Rosson
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Department of Molecular Oncology, Roche Institute of Molecular Biology, Nutley, NJ 07110.
Reddy
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D000595:Amino Acid Sequence; D000818:Animals; D009189:Avian Myeloblastosis Virus / Q000235:genetics / Q000648:ultrastructure; D001483:Base Sequence; D004247:DNA; D005786:Gene Expression Regulation; D005814:Genes, Viral; D051379:Mice; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000235:genetics; D009857:Oncogenes; D011519:Proto-Oncogenes; D012333:RNA, Messenger; D012367:RNA, Viral
D012333:RNA, Messenger; D012367:RNA, Viral; D004247:DNA