Essential roles of the Bcl-2 family of proteins in caspase-2-induced apoptosis

Zhonghua Gao, Yufang Shao, Xuejun Jiang

Research output: Contribution to journalArticle

60 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)38271-38275
Number of pages5
JournalJournal of Biological Chemistry
Volume280
Issue number46
DOIs
StatePublished - Dec 1 2005

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Caspase 2
Apoptosis
Proteins
Cytochromes c
Mitochondria
BH3 Interacting Domain Death Agonist Protein
Cells
Gene Deletion
Caspases
Cell culture
Tumors
Cultured Cells
Assays
Neoplasms

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Gao, Zhonghua ; Shao, Yufang ; Jiang, Xuejun. / Essential roles of the Bcl-2 family of proteins in caspase-2-induced apoptosis. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 46. pp. 38271-38275.
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Essential roles of the Bcl-2 family of proteins in caspase-2-induced apoptosis. / Gao, Zhonghua; Shao, Yufang; Jiang, Xuejun.

In: Journal of Biological Chemistry, Vol. 280, No. 46, 01.12.2005, p. 38271-38275.

Research output: Contribution to journalArticle

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