Bcl-2 regulates a caspase-3/caspase-2 apoptotic cascade in cytosolic extracts

Eileithyia Swanton, Peter Savory, Sabina Cosulich, Paul Clarke, Philip Woodman (Lead / Corresponding author)

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Apoptosis is accompanied by the activation of a number of apoptotic proteases (caspases) which selectively cleave specific cellular substrates. Caspases themselves are zymogens which are activated by proteolysis. It is widely believed that 'initiator' caspases are recruited to and activated within apoptotic signalling complexes, and then cleave and activate downstream 'effector' caspases. While activation of the effector caspase, caspase-3, has indeed been observed as distal to activation of several different initiator caspases, evidence for a further downstream proteolytic cascade is limited. In particular, there is little evidence that cellular levels of caspase-3 that are activated via one pathway are sufficient to cleave and activate other initiator caspases. To address this issue, the ability of caspase-3, activated upon addition to cytosolic extracts of cytochrome c, to cause cleavage of caspase-2 was investigated. It was demonstrated that cleavage of caspase-2 follows, and is dependent upon, activation of caspase-3. Moreover, the activation of both caspases was inhibited by Bcl-2. Together, these data indicate that Bcl-2 can protect cells from apoptosis by acting at a point downstream from release of mitochondrial cytochrome c, thereby preventing a caspase-3 dependent proteolytic cascade.

Original languageEnglish
Pages (from-to)1781-1787
Number of pages7
JournalOncogene
Volume18
Issue number10
DOIs
Publication statusPublished - 11 Mar 1999

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Caspase 2
Caspase 3
Initiator Caspases
Caspases
Effector Caspases
Cytochromes c
Apoptosis
Enzyme Precursors
Proteolysis
Peptide Hydrolases

Keywords

  • Caspase cleavage
  • Cytochrome c
  • dATP
  • ICH-1

Cite this

Swanton, Eileithyia ; Savory, Peter ; Cosulich, Sabina ; Clarke, Paul ; Woodman, Philip. / Bcl-2 regulates a caspase-3/caspase-2 apoptotic cascade in cytosolic extracts. In: Oncogene. 1999 ; Vol. 18, No. 10. pp. 1781-1787.
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Swanton, E, Savory, P, Cosulich, S, Clarke, P & Woodman, P 1999, 'Bcl-2 regulates a caspase-3/caspase-2 apoptotic cascade in cytosolic extracts', Oncogene, vol. 18, no. 10, pp. 1781-1787. https://doi.org/10.1038/sj.onc.1202490

Bcl-2 regulates a caspase-3/caspase-2 apoptotic cascade in cytosolic extracts. / Swanton, Eileithyia; Savory, Peter; Cosulich, Sabina; Clarke, Paul; Woodman, Philip (Lead / Corresponding author).

In: Oncogene, Vol. 18, No. 10, 11.03.1999, p. 1781-1787.

Research output: Contribution to journalArticle

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