The underlying premise of this work is that inhibition of proteolysis observed during aging results in an inhibition of cell proliferation responses, as exemplified by reduced immune function, liver regeneration, and wound-healing. In this proposal, it is hypothesized that inhibition of cysteine proteinases by thiostatin results in impairment in the cell's ability to respond to mitogenic stimuli. To test this, it is proposed to identify: (1) the site(s) within the cell cycle that are affected by thiostatin overexpression, and (2) the molecular mechanisms responsible for inhibition of the MAP kinase pathway of signal transduction in thiostatin-producing cells.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
7R01AG013902-03
Application #
6032818
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Finkelstein, David B
Project Start
1997-08-15
Project End
1998-12-31
Budget Start
1998-11-11
Budget End
1998-12-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Mcp Hahnemann University
Department
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19102
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Torres, C; Li, M; Walter, R et al. (2001) T-kininogen inhibits fibroblast proliferation in the G(1) phase of the cell cycle. Exp Cell Res 269:171-9
Torres, C; Li, M; Walter, R et al. (2000) Modulation of the ERK pathway of signal transduction by cysteine proteinase inhibitors. J Cell Biochem 80:23-Nov

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