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Sci. Signal., 6 October 2009
Vol. 2, Issue 91, p. pe62
[DOI: 10.1126/scisignal.291pe62]

PERSPECTIVES

Apoptosis: Calling Time on Apoptosome Activity

Colin Adrain1 and Seamus J. Martin2*

1 Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK.
2 Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland.

Abstract: Apoptosis is a controlled form of cellular demolition, catalyzed by a family of cysteine proteases called caspases. In response to diverse proapoptotic stimuli, caspase-9 is recruited and activated within an oligomeric complex called the apoptosome. The apoptosome drives autocatalytic processing of caspase-9, triggering a proteolytic caspase cascade that results in the biochemical and morphological changes characteristic of cell death. It is unclear why caspase-9 undergoes autocatalytic processing following apoptosome recruitment, because interdomain processing is dispensable for caspase-9 activity. A study has shed light on this issue by demonstrating that caspase-9 processing within the apoptosome promotes its displacement from the complex, leading to inactivation of this protease. Thus, autoprocessing of caspase-9 within the apoptosome serves as a "molecular timer" that limits the proteolytic activity of this complex through displacement of bound caspase-9 molecules. This timer mechanism may enable cells to prevent low amounts of apoptosome activation from spiraling out of control unless sufficient numbers of apoptosomes are assembled within a particular time window, which would drive full-blown caspase activation and apoptosis.

* Corresponding author. E-mail, martinsj{at}tcd.ie

Citation: C. Adrain, S. J. Martin, Apoptosis: Calling Time on Apoptosome Activity. Sci. Signal. 2, pe62 (2009).

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