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Mutations in the DNA-binding and transcriptional activation domains of v-Myb cooperate in transformation.

Abstract
The v-Myb protein encoded by avian myeloblastosis virus causes oncogenic transformation of monoblastic cells committed to the monocyte/macrophage lineage. v-Myb is a doubly truncated form of its normal cellular counterpart, c-Myb. In addition to its N- and C-terminal deletions, v-Myb contains a number of amino acid substitutions relative to c-Myb. We have previously shown that neither overexpression of c-Myb nor introduction of these amino acid substitutions into c-Myb is sufficient for transformation of myelomonocytic cells. However, a doubly truncated form of c-Myb which lacked these substitutions transformed myeloblastic cells that appeared to be committed to the granulocytic pathway. We demonstrate here that mutations in both the DNA-binding and transcriptional activation domains of v-Myb are required for transformation of rapidly growing monoblasts rather than more slowly growing myeloblasts. These rapidly growing monoblasts do not express mim-1, a target gene for the Gag-Myb-Ets protein of E26 leukemia virus, or C/EBP proteins which cooperate with Myb to activate mim-1 expression. Furthermore, v-Myb proteins which contain both sets of these mutations are weaker transcriptional activators relative to proteins which lack these mutations. These results support a model in which amino acid substitutions in v-Myb have been selected for their ability to activate only a subset of those genes which can be activated by a doubly truncated form of c-Myb. In particular, mim-1 appears to represent a class of genes whose expression was selected against during the development of an increasingly virulent strain of avian myeloblastosis virus by passage in animals.
AuthorsP W Dini, J T Eltman, J S Lipsick
JournalJournal of virology (J Virol) Vol. 69 Issue 4 Pg. 2515-24 (Apr 1995) ISSN: 0022-538X [Print] UNITED STATES
PMID7884901 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • CCAAT-Enhancer-Binding Proteins
  • DNA, Viral
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Oligodeoxyribonucleotides
  • Oncogene Proteins v-myb
  • Proteins
  • Retroviridae Proteins, Oncogenic
  • Acetyltransferases
  • mim-1 protein, Gallus gallus
Topics
  • Acetyltransferases
  • Base Sequence
  • CCAAT-Enhancer-Binding Proteins
  • Cell Transformation, Viral
  • DNA, Viral (genetics, metabolism)
  • DNA-Binding Proteins (genetics, metabolism)
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins (genetics, metabolism)
  • Oligodeoxyribonucleotides
  • Oncogene Proteins v-myb
  • Protein Binding
  • Proteins (genetics, metabolism)
  • Retroviridae Proteins, Oncogenic (genetics, metabolism)
  • Transcriptional Activation (genetics)

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