|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.
|Appears in Collections:||分子醫學研究所|
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