Abstract

The long range goal of this project is the analysis of the function of v-rel in lymphoid tissue. Of primary interest is the role v-rel plays in the induction of mature B-cell tumors. Experiments are designed that will define cell phenotypes that are permissive or non-permissive for v- rel-induced neoplasia. Using site-directed mutagenesis, conditional and non-conditional mutants will be constructed in the v-rel 57 kD protein. Mutant v-rel proteins will be characterized using biochemical assays for their association with in vitro kinase activity, their interaction with a 40 kD cellular protein and their location in the nuclear or cytoplasmic compartments of the infected cell. Monoclonal antibodies capable of recognizing different epitopes distributed throughout v-rel will be isolated. The mutant proteins will be characterized using the alpha v-rel monoclonal antibodies in order to analyze them for the presence of defined epitopes. Using the combined biochemical analyses of mutant v-rel proteins and the definition of structural epitopes that are associated with specific functional domains, the functional domains essential for v-rel-induced tumor development can be identified.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA041450-06
Application #
3181927
Study Section
Virology Study Section (VR)
Project Start
1986-03-01
Project End
1994-07-31
Budget Start
1991-08-01
Budget End
1992-07-31
Support Year
6
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
West Virginia University
Department
Type
Schools of Medicine
DUNS #
191510239
City
Morgantown
State
WV
Country
United States
Zip Code
26506

  Publications

Zhang, G; Humphries, E H (1996) v-rel and c-rel induce a membrane protein, p75, on avian hematopoietic cells. Oncogene 12:1153-7
Zhang, G; Slaughter, C; Humphries, E H (1995) v-rel Induces ectopic expression of an adhesion molecule, DM-GRASP, during B-lymphoma development. Mol Cell Biol 15:1806-16
Hrdlickova, R; Nehyba, J; Roy, A et al. (1995) The relocalization of v-Rel from the nucleus to the cytoplasm coincides with induction of expression of Ikba and nfkb1 and stabilization of I kappa B-alpha. J Virol 69:403-13
Filardo, E J; Lee, M F; Humphries, E H (1994) Structural genes, not the LTRs, are the primary determinants of reticuloendotheliosis virus A-induced runting and bursal atrophy. Virology 202:116-28
Hrdlickova, R; Nehyba, J; Humphries, E H (1994) In vivo evolution of c-rel oncogenic potential. J Virol 68:2371-82
Nehyba, J; Hrdlickova, R; Humphries, E H (1994) Evolution of the oncogenic potential of v-rel: rel-induced expression of immunoregulatory receptors correlates with tumor development and in vitro transformation. J Virol 68:2039-50
Hrdlickova, R; Nehyba, J; Humphries, E H (1994) v-rel induces expression of three avian immunoregulatory surface receptors more efficiently than c-rel. J Virol 68:308-19
Humphries, E H; Zhang, G (1992) V-rel and C-rel modulate the expression of both bursal and non-bursal antigens on avian B-cell lymphomas. Curr Top Microbiol Immunol 182:475-83
Barth, C F; Ewert, D L; Olson, W C et al. (1990) Reticuloendotheliosis virus REV-T(REV-A)-induced neoplasia: development of tumors within the T-lymphoid and myeloid lineages. J Virol 64:6054-62
Huffnagle, G B; Ratcliffe, M J; Humphries, E H (1989) Bu-2, a novel avian cell surface antigen on B cells and a population of non-lymphoid cells, is expressed homogeneously in germinal centers. Hybridoma 8:589-604

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