https://scholars.lib.ntu.edu.tw/handle/123456789/160061
Title: | Tgf-Beta Induces Apoptosis through Smad-Mediated Expression of Dap-Kinase | Authors: | CHEN, RUEY-HWA | Keywords: | GROWTH-FACTOR-BETA;PROGRAMMED CELL-DEATH;TRANSFORMING GROWTH -FACTOR-BETA-1;FUNCTIONAL COOPERATION;SIGNALING PATHWAYS;DOWN-REGULATION | Issue Date: | 2002 | Journal Volume: | v.4 | Journal Issue: | n.1 | Start page/Pages: | 51-58 | Source: | NATURE CELL BIOLOGY | Abstract: | Transforming growth factor-beta (TGF-beta) and TGF-beta- related factors induce apoptosis in a variety of tissues; however, the mechanism underlying this induction is largely unknown. Here, we demonstrate that TGF-beta induces the expression of the death-associated protein kinase ( DAP- kinase) as an immediate early response in cells that undergo apoptosis in response to TGF-beta. DAP-kinase is a positive mediator of apoptosis induced by certain cytokines and oncogenes. We show that the DAP -kinase promoter is activated by TGF-beta through the action of Smad2, Smad3 and Smad4. Overexpression of DAP-kinase triggers apoptosis in the absence of TGF-beta, whereas inhibition of DAP-kinase activity protects cells from TGF-beta-induced apoptosis, blocks TGF-beta-induced release of cytochrome c from mitochondria and prevents TGF-beta-induced dissipation of the mitochondrial membrane potential. Our findings indicate that DAP- kinase mediates TGF-beta-dependent apoptosis by linking Smads to mitochondrial-based pro-apoptotic events. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/95069 |
Appears in Collections: | 分子醫學研究所 |
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