CHARACTERIZATION OF THE V-ERB B ONCOGENE PROTEIN OF AEV

  • Privalsky, Martin L, (PI)

Project: Research project

Description

The ultimate goal of the experiments proposed here is a better
understanding of the mechanism(s) by which avian erythroblastosis virus
(AEV) transforms host cells to an oncogenic state. A single locus in the
AEV genome, v-erb B, is both required and sufficient for oncogenesis by
this virus; the protein product of the v-erb B locus has been identified
and partially characterized. The work proposed here seeks to better relate
the biochemical and structural properties of the v-erb B protein to the
oncogenic abilities of AEV. Three general experimental areas will be
pursued: (1) The v-erb B gene will be subjected to in vitro, site-directed
mutagenesis to identify regions essential for oncogenesis. The biological
effect of various specific genetic lesions will be ascertained. (2) The biochemical properties of the v-erb B protein derived from
wild-type and mutant-infected cells will be characterized and compared, and
an attempt will be made to correlate specific genetic lesions (from 1,
above) with altered structural, biochemical, and oncogenic properties of
the v-erb B protein. (3) Chimeras between the v-erb B and v-src oncogenes will be constructed to
explore the functional significance of the structural relatedness
ascertained between these two retroviral loci. These experiments will provide important information on the molecular
biology of the v-erb B protein and will serve as a foundation for a better
understanding of the role of this protein in the induction of neoplasms by
AEV. This work may also have important implications for comprehension of
processes controlling the growth and proliferation of normal eukaryotic
cells: the v-erb B protein is closely related (at the amino acid sequence
level) to an epidermal growth factor receptor found in uninfected cells.
StatusFinished
Effective start/end date7/1/855/31/94

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Oncogene Proteins
Alpharetrovirus
Epidermal Growth Factor Receptor
Carcinogenesis
IgA receptor
Peptides
src Genes
Site-Directed Mutagenesis
Oncogenes
Growth
Aptitude
Stem Cells
Phenotype
Proteins

Keywords

  • Medicine(all)