Transforming Growth Factor β1 Induces Apoptosis through Cleavage of BAD in a Smad3-Dependent Mechanism in FaO Hepatoma Cells
- 1 March 2002
- journal article
- Published by Taylor & Francis in Molecular and Cellular Biology
- Vol. 22 (5) , 1369-1378
- https://doi.org/10.1128/mcb.22.5.1369-1378.2002
Abstract
Transforming growth factor β (TGF-β) induces apoptosis in a variety of cells. We have previously shown that TGF-β1 rapidly induces apoptosis in the FaO rat hepatoma cell line. We have now studied the effect of TGF-β1 on the expression of different members of the Bcl-2 family in these cells. We observed no detectable changes in the steady-state levels of Bcl-2, Bcl-XL, and Bax. However, TGF-β1 induced caspase-dependent cleavage of BAD at its N terminus to generate a 15-kDa truncated protein. Overexpression of the 15-kDa truncated BAD protein enhanced TGF-β1-induced apoptosis, whereas a mutant BAD resistant to caspase 3 cleavage blocked TGF-β1-induced apoptosis. Overexpression of Smad3 dramatically enhanced TGF-β1-induced cleavage of BAD and apoptosis, whereas antisense Smad3 blocked TGF-β1-induced apoptosis and BAD cleavage. These results suggest that TGF-β1 induces apoptosis through the cleavage of BAD in a Smad3-dependent mechanism.Keywords
This publication has 52 references indexed in Scilit:
- Bcl-xL Blocks Transforming Growth Factor-β1-induced Apoptosis by Inhibiting Cytochrome c Release and Not by Directly Antagonizing Apaf-1-dependent Caspase Activation in Prostate Epithelial CellsPublished by Elsevier ,2001
- Caspase Cleavage Enhances the Apoptosis-Inducing Effects of BADMolecular and Cellular Biology, 2001
- Liver toxicity and apoptosis: role of TGF-β1, cytochrome c and the apoptosomeToxicology Letters, 2001
- Transforming Growth Factor-β1 Induces Apoptosis Independently of p53 and Selectively Reduces Expression of Bcl-2 in Multipotent Hematopoietic CellsPublished by Elsevier ,2000
- Critical Role of Smads and AP-1 Complex in Transforming Growth Factor-β-dependent ApoptosisJournal of Biological Chemistry, 2000
- Cdc2 and Cdk2 Kinase Activated by Transforming Growth Factor-β1 Trigger Apoptosis through the Phosphorylation of Retinoblastoma Protein in FaO Hepatoma CellsJournal of Biological Chemistry, 1999
- Bax and Adenine Nucleotide Translocator Cooperate in the Mitochondrial Control of ApoptosisScience, 1998
- Human Smad3 and Smad4 Are Sequence-Specific Transcription ActivatorsPublished by Elsevier ,1998
- ICE-like protease (caspase) is involved in transforming growth factor β1-mediated apoptosis in FaO rat hepatoma cell lineHepatology, 1998
- TGFβ1 Inhibits NF-κB/Rel Activity Inducing Apoptosis of B Cells: Transcriptional Activation of IκBαImmunity, 1996