Essential roles of the Bcl-2 family of proteins in caspase-2-induced apoptosis Journal Article
| Authors: | Gao, Z.; Shao, Y.; Jiang, X. |
| Article Title: | Essential roles of the Bcl-2 family of proteins in caspase-2-induced apoptosis |
| Abstract: | Caspase-2 is an initiating caspase required for stress-induced apoptosis in various human cancer cells. Recent studies suggest that it can mediate the death function of tumor suppressor p53 and is activated by a multimeric protein complex, PIDDosome. However, it is not clear how caspase-2 exerts its apoptotic function in cells and whether its enzymatic activity is required for the apoptotic function. In this study, we used both in vitro mitochondrial cytochrome c release assays and cell culture apoptosis analyses to investigate the mechanism by which caspase-2 induces apoptosis. We show that active caspase-2, but neither a catalytically mutated caspase-2 nor active caspase-2 with its inhibitor, can cause cytochrome c release. Caspase-2 failed to induce cytochrome c release from mitochondria with Bid-/- background, and the release could be restored by addition of the wild-type Bid protein, but not by Bid with the caspase-2 cleavage site mutated. Caspase-2 was not able to induce cytochrome c release from Bax-/-Bak-/- mitochondria either. In cultured cells, gene deletion of Bax/Bak or Bid abrogated apoptosis induced by overexpression of caspase-2. Collectively, these results indicate that proteolytic activation of Bid and the subsequent induction of the mitochondrial apoptotic pathway through Bax/Bak is essential for apoptosis triggered by caspase-2. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc. |
| Keywords: | protein expression; human cell; gene deletion; proteins; mouse; animal; metabolism; animals; mice; protein bcl 2; apoptosis; enzyme inhibition; cell line; rna interference; enzyme activation; in vitro study; caspase; hela cell; caspases; cell line, tumor; hela cells; protein p53; transgenic mouse; mice, transgenic; biosynthesis; cell culture; tumors; escherichia coli; tumor cell line; plasmid; cell line, transformed; tumor suppressor protein p53; plasmids; mutagenesis, site-directed; tumor suppressor; catalysis; site directed mutagenesis; mitochondria; bh3 interacting domain death agonist protein; proto-oncogene proteins c-bcl-2; mitochondrion; mutagenesis; complementary dna; dna, complementary; cells; cytochrome c; cytochromes c; protein bax; protein bid; protein bak; cytochrome; bcl-2 homologous antagonist-killer protein; bcl-2-associated x protein; enzymatic activity; reaction kinetics; growth kinetics; mitochondrial cytochrome; caspase 2; cytochromes |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 280 |
| Issue: | 46 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2005-11-18 |
| Start Page: | 38271 |
| End Page: | 38275 |
| Language: | English |
| DOI: | 10.1074/jbc.M506488200 |
| PUBMED: | 16172118 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 41" - "Export Date: 24 October 2012" - "CODEN: JBCHA" - "Source: Scopus" |
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