Abstract

The cell surface of animal cells has been implicated to participate in a number of important biological processes unique to multicellular organisms. It is generally assumed that the cell surface, either based on its detailed chemistry, topological rearrangements or by processes including assembly, turnover and dynamic interactions with other organelles, plays a key role in the regulation of cellular proliferation and in cell-cell interaction in normal and malignant cells.
The aim of the research project is to elucidate the structure and functions of mammalian cell surface through the isolation and biochemical characterization of somatic cell mutants. More specifically, we plan; a. to isolate and characterize CHO mutants resistant to cytotoxins, including plant lectins and microbial toxins; b. to isolate and characterize CHO mutants altered in the structural and functional integrity to cytoskeleton-membrane complex by using chemicals believed to interact with surface modulating assemblies; and c. to ascertain the physiological consequences of these mutations. By ascertaining the cause-effect relationship between the alteration in cell surface component and the loss of growth control, we may gain a better insight into the pathogenesis of neoplasia at the cellular and molecular level.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM028810-06
Application #
3276112
Study Section
Cognition and Perception Study Section (CP)
Project Start
1980-12-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
6
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
U.S. Uniformed Services University of Health Science
Department
Type
Schools of Medicine
DUNS #
City
Bethesda
State
MD
Country
United States
Zip Code
20814

  Publications

Nambiar, M P; Murugesan, R; Wu, H C (1998) Inhibition of the cytotoxicity of protein toxins by a novel plant metabolite, mansonone-D. J Cell Physiol 176:40-9
Oda, T; Wu, H C (1995) Protective effect of cell-permeable ceramide analogs against modeccin, ricin, Pseudomonas toxin, and diphtheria toxin. Exp Cell Res 221:1-10
Oda, T; Chen, C H; Wu, H C (1995) Ceramide reverses brefeldin A (BFA) resistance in BFA-resistant cell lines. J Biol Chem 270:4088-92
Nambiar, M P; Wu, H C (1995) Ilimaquinone inhibits the cytotoxicities of ricin, diphtheria toxin, and other protein toxins in Vero cells. Exp Cell Res 219:671-8
Oda, T; Wu, H C (1994) Effect of lovastatin on the cytotoxicity of ricin, modeccin, Pseudomonas toxin, and diphtheria toxin in brefeldin A-sensitive and -resistant cell lines. Exp Cell Res 212:329-37
Oswald, E; Sugai, M; Labigne, A et al. (1994) Cytotoxic necrotizing factor type 2 produced by virulent Escherichia coli modifies the small GTP-binding proteins Rho involved in assembly of actin stress fibers. Proc Natl Acad Sci U S A 91:3814-8
Nambiar, M P; Oda, T; Chen, C et al. (1993) Involvement of the Golgi region in the intracellular trafficking of cholera toxin. J Cell Physiol 154:222-8
Oda, T; Wu, H C (1993) Cerulenin inhibits the cytotoxicity of ricin, modeccin, Pseudomonas toxin, and diphtheria toxin in brefeldin A-resistant cell lines. J Biol Chem 268:12596-602
Chen, C H; Kuwazuru, Y; Yoshida, T et al. (1992) Isolation and characterization of a brefeldin A-resistant mutant of monkey kidney Vero cells. Exp Cell Res 203:321-8
Sugai, M; Chen, C H; Wu, H C (1992) Staphylococcal ADP-ribosyltransferase-sensitive small G protein is involved in brefeldin A action. J Biol Chem 267:21297-9

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