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T-Kininogen Inhibits Fibroblast Proliferation in the G1 Phase of the Cell Cycle
Journal article   Peer reviewed

T-Kininogen Inhibits Fibroblast Proliferation in the G1 Phase of the Cell Cycle

Claudio Torres, Min Li, Robin Walter and Felipe Sierra
Experimental cell research, v 269(2)
01 Oct 2001

Abstract

cell cycle cysteine proteinases MAP kinase proliferation T-kininogen
By using synthetic protease inhibitors, several investigators have demonstrated that cysteine proteinases are required for cell proliferation. Kininogens are potent and specific physiological inhibitors of cysteine proteinases. We have used several mouse fibroblast-derived cell lines that express biologically active T-kininogen under the control of the mouse metallothionein promoter to test its effect on cell proliferation. Our results indicate that expression of T-kininogen results in diminished proliferative capacity, as measured by reduced cell numbers, both in logarithmically growing cultures and in G0 cells induced to proliferate in response to serum. Furthermore, both fluorescence-activated cell sorting (FACS) analysis and incorporation of radioactive precursors into DNA suggest that the cells are unable to progress from G0 through the S phase of the cell cycle in response to serum stimulation. However, we find that T-kininogen-expressing cell lines are still capable of responding to growth factors present in the serum, both by activating the ERK pathway and by expressing early genes, such as c-Fos and c-Jun. Thus, our results suggest that inhibition of cysteine proteinases by T-kininogen leads to inhibition of cell proliferation between the G1 and S phases of the cell cycle.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Cell Biology
Oncology
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