Literature DB >> 11839804

Transforming growth factor beta 1 induces apoptosis through cleavage of BAD in a Smad3-dependent mechanism in FaO hepatoma cells.

Byung-Chul Kim1, Mizuko Mamura, Kyeong Sook Choi, Bruno Calabretta, Seong-Jin Kim.   

Abstract

Transforming growth factor beta (TGF-beta) induces apoptosis in a variety of cells. We have previously shown that TGF-beta 1 rapidly induces apoptosis in the FaO rat hepatoma cell line. We have now studied the effect of TGF-beta 1 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-X(L), and Bax. However, TGF-beta 1 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-beta 1-induced apoptosis, whereas a mutant BAD resistant to caspase 3 cleavage blocked TGF-beta 1-induced apoptosis. Overexpression of Smad3 dramatically enhanced TGF-beta 1-induced cleavage of BAD and apoptosis, whereas antisense Smad3 blocked TGF-beta 1-induced apoptosis and BAD cleavage. These results suggest that TGF-beta 1 induces apoptosis through the cleavage of BAD in a Smad3-dependent mechanism.

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Year:  2002        PMID： 11839804      PMCID： PMC134700          DOI： 10.1128/MCB.22.5.1369-1378.2002

Source DB:  PubMed          Journal:  Mol Cell Biol        ISSN： 0270-7306            Impact factor:   4.272


  48 in total

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3.  Versatility of BCR/ABL-expressing leukemic cells in circumventing proapoptotic BAD effects.

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Journal:  J Biol Chem       Date:  1999-11-05       Impact factor: 5.157

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  21 in total

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3.  Expression and regulation of CD97 in colorectal carcinoma cell lines and tumor tissues.

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Review 4.  Role of Smad signaling in kidney disease.

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6.  PTHrP is a novel mediator for TGF-β-induced apoptosis.

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7.  Blockade of Autocrine TGF-β Signaling Inhibits Stem Cell Phenotype, Survival, and Metastasis of Murine Breast Cancer Cells.

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8.  Runx1 is a co-activator with FOXO3 to mediate transforming growth factor beta (TGFbeta)-induced Bim transcription in hepatic cells.

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Review 9.  Multiple functions of BCL-2 family proteins.

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