Apoptosis: calling time on apoptosome activity.
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.
Adrain
Colin
C
Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK.
Martin
Seamus J
SJ
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053478:Apoptosomes / Q000378:metabolism*; D053477:Apoptotic Protease-Activating Factor 1 / Q000378:metabolism; D001665:Binding Sites; D053453:Caspase 9 / Q000378:metabolism; D002384:Catalysis; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D013997:Time Factors
D053478:Apoptosomes; D053477:Apoptotic Protease-Activating Factor 1; D053453:Caspase 9