Abstract

The central theme of this program is the role of retroviruses and retrovirus-related oncogenes in neoplastic change. The grant consists of seven individual projects which address the issue across a broad front. Project 1 is concerned with the location and function within the cell of tyrosine protein kinases encoded by a number of viral oncogenes and the molecules which serve as the substrates for these enzymes. Project 2 attempts to exploit the suppression of gene expression by anti-sense RNA to determine whether this strategy can be used to manipulate the expression of c-myc and c-ras oncogenes. Project 3 will explore the role of tyrosine protein kinases in the action of polypeptide hormones on differentiation and cell growth. Project 4 will involve purification and microinjection analysis of the protein of the myc oncogene. Project 5 concerns the chromatin structure of the myc oncogene and effects of retroviral integration events on myc chromatin structure and expression. Project 6 will examine the role of specific domains of the v-myc gene in the oncogenicity of avian myelocytomatosis virus. Project 7 will attempt to determine the role of two oncogenes, myc and Blym-1, in specific stages of virus induced lymphomagenesis in the bursa of Fabricius in chickens.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA028151-07
Application #
3093219
Study Section
Cancer Special Program Advisory Committee (CAK)
Project Start
1980-07-01
Project End
1991-08-31
Budget Start
1986-09-30
Budget End
1987-08-31
Support Year
7
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109

  Publications

Fiore, R S; Bayer, V E; Pelech, S L et al. (1993) p42 mitogen-activated protein kinase in brain: prominent localization in neuronal cell bodies and dendrites. Neuroscience 55:463-72
Kazlauskas, A; Kashishian, A; Cooper, J A et al. (1992) GTPase-activating protein and phosphatidylinositol 3-kinase bind to distinct regions of the platelet-derived growth factor receptor beta subunit. Mol Cell Biol 12:2534-44
Posada, J; Cooper, J A (1992) Requirements for phosphorylation of MAP kinase during meiosis in Xenopus oocytes. Science 255:212-5
Kashishian, A; Kazlauskas, A; Cooper, J A (1992) Phosphorylation sites in the PDGF receptor with different specificities for binding GAP and PI3 kinase in vivo. EMBO J 11:1373-82
Luscher, B; Brizuela, L; Beach, D et al. (1991) A role for the p34cdc2 kinase and phosphatases in the regulation of phosphorylation and disassembly of lamin B2 during the cell cycle. EMBO J 10:865-75
Carlberg, K; Tapley, P; Haystead, C et al. (1991) The role of kinase activity and the kinase insert region in ligand-induced internalization and degradation of the c-fms protein. EMBO J 10:877-83
Neiman, P E; Thomas, S J; Loring, G (1991) Induction of apoptosis during normal and neoplastic B-cell development in the bursa of Fabricius. Proc Natl Acad Sci U S A 88:5857-61
Blackwood, E M; Eisenman, R N (1991) Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. Science 251:1211-7
Posada, J; Sanghera, J; Pelech, S et al. (1991) Tyrosine phosphorylation and activation of homologous protein kinases during oocyte maturation and mitogenic activation of fibroblasts. Mol Cell Biol 11:2517-28
Blackwood, E M; Luscher, B; Kretzner, L et al. (1991) The Myc:Max protein complex and cell growth regulation. Cold Spring Harb Symp Quant Biol 56:109-17

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