Article abstract
Nature Cell Biology 4, 51 - 58 (2001)
Published online: 10 December 2001 | doi:10.1038/ncb731
There is an Erratum (April 2002) associated with this Article.
TGF-
induces apoptosis through Smad-mediated expression of DAP-kinase
Chuan-Wei Jang1, Chun-Hau Chen1, Chun-Chieh Chen1, Jia-yun Chen1, Yi-Hsien Su1 & Ruey-Hwa Chen1
Abstract
Transforming growth factor-
(TGF-) and TGF--related factors induce apoptosis in a variety of tissues; however, the mechanism underlying this induction is largely unknown. Here, we demonstrate that TGF- 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-. 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- through the action of Smad2, Smad3 and Smad4. Overexpression of DAP-kinase triggers apoptosis in the absence of TGF-, whereas inhibition of DAP-kinase activity protects cells from TGF--induced apoptosis, blocks TGF--induced release of cytochrome c from mitochondria and prevents TGF--induced dissipation of the mitochondrial membrane potential. Our findings indicate that DAP-kinase mediates TGF--dependent apoptosis by linking Smads to mitochondrial-based pro-apoptotic events.
- Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan
Correspondence to: Ruey-Hwa Chen1 e-mail: rhchen@ha.mc.ntu.edu.tw
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