Ordering of caspases in cells undergoing apoptosis by the intrinsic pathway

S. Inoue, G. Browne, G. Melino, G. M. Cohen

Research output: Contribution to journalArticlepeer-review

Abstract

Caspases are a family of aspartate-specific cysteine proteases responsible for the biochemical and morphological changes that occur during the execution phase of apoptosis. The hierarchical ordering of caspases has been clearly established using dATP-activated cell lysates to model the intrinsic pathway induced by initial mitochondrial perturbation. In this model, caspase-9, the apical caspase, directly processes and activates the effector caspases, caspase-3 and -7, and then active caspase-3 but not caspase-7, processes caspase-2 and -6, and subsequently the activated caspase-6 processes caspase-8 and -10. To address the possibility that this model in vitro system might not reflect the precise ordering of caspases in intact cells, we have examined this possibility in cells induced to undergo apoptosis by activation of the intrinsic pathway. We have used caspase deficient cells, small interference RNA for caspase-6 and -7, and a specific caspase-3 inhibitor. In contrast to the earlier in vitro studies, we now show that in intact cells caspase-7 can also directly process and activate caspase-2 and -6. The processing of caspase-2 and -6 occurs within the cytoplasm and active caspase-6 is then responsible for both the processing of caspase-8 and the cleavage of caspase-6 substrates, including lamin A/C.

Original languageEnglish
Pages (from-to)1053-1061
Number of pages9
JournalCell Death and Differentiation
Volume16
Issue number7
DOIs
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'Ordering of caspases in cells undergoing apoptosis by the intrinsic pathway'. Together they form a unique fingerprint.

Cite this