Abstract

Studies will be undertaken to gain further insight into the mechanism of action of the interferons (IFNs). Proposed studies will characterize the antiviral and antiproliferative phenotypes of cells which, as a result of transfection, produce the IFN-induced gp96, 67kD, 56kD, or 42kD proteins. In addition, the cDNAs encoding these proteins will be used to: 1) study the genes encoding these proteins; 2) characterize the promoters responsible for their responsiveness to the IFNs; and 3) determine the chromosomal localization of each gene. Characterization of the IFN-induced 56,000 dalton protein has resulted in the demonstration that this protein is a tryptophanyl tRNA synthetase. Studies proposed will evaluate the relatedness of this protein to the mammalian peptide chain release factor and the role this protein plays in the biological actions of the IFNs. The characterizations of genes and their products that are up-regulated in response to the IFNs are being undertaken to provide insight into the mechanisms by which the IFNs mediate their effects and to enable the development of a methodology by which the responsiveness of tumor tissues to the anticellular effects of the IFNs can be established in vitro prior to their use as therapeutic agents.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA038661-10A2
Application #
3176832
Study Section
Virology Study Section (VR)
Project Start
1989-09-30
Project End
1997-05-31
Budget Start
1993-06-02
Budget End
1994-05-31
Support Year
10
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Fordham University
Department
Type
Other Domestic Higher Education
DUNS #
City
Bronx
State
NY
Country
United States
Zip Code
10458

  Publications

Anderson, S L; Carton, J M; Lou, J et al. (1999) Interferon-induced guanylate binding protein-1 (GBP-1) mediates an antiviral effect against vesicular stomatitis virus and encephalomyocarditis virus. Virology 256:8-14
Anderson, S L; Carton, J M; Zhang, X et al. (1999) Genomic organization and chromosomal localization of a new member of the murine interferon-induced guanylate-binding protein family. J Interferon Cytokine Res 19:487-94
Lou, J; Anderson, S L; Xing, L et al. (1994) Suppression of mitochondrial mRNA levels and mitochondrial function in cells responding to the anticellular action of interferon. J Interferon Res 14:33-40
Bandyopadhyay, S K; Kumar, R; Rubin, B Y et al. (1992) Interferon-inducible gene expression in HL-60 cells: effects of the state of differentiation. Cell Growth Differ 3:369-75
Murray, H W; Szuro-Sudol, A; Wellner, D et al. (1989) Role of tryptophan degradation in respiratory burst-independent antimicrobial activity of gamma interferon-stimulated human macrophages. Infect Immun 57:845-9
Rubin, B Y; Anderson, S L; Lunn, R M et al. (1989) Induction of proteins in interferon-alpha- and interferon-gamma-treated polymorphonuclear leukocytes. J Leukoc Biol 45:396-400
Rubin, B Y; Anderson, S L; Lunn, R M et al. (1989) Fragmentation of cellular DNA is a nonspecific indicator of responsiveness to tumor necrosis factor. J Biol Response Mod 8:553-9
Squires, K E; Schreiber, R D; McElrath, M J et al. (1989) Experimental visceral leishmaniasis: role of endogenous IFN-gamma in host defense and tissue granulomatous response. J Immunol 143:4244-9
Rubin, B Y; Anderson, S L; Lunn, R M et al. (1988) Tumor necrosis factor and IFN induce a common set of proteins. J Immunol 141:1180-4
Murray, H W; Scavuzzo, D A; Kelly, C D et al. (1988) T4+ cell production of interferon gamma and the clinical spectrum of patients at risk for and with acquired immunodeficiency syndrome. Arch Intern Med 148:1613-6

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