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Exp Cell Res. 2005 Jan 1;302(1):115-28.

Caspase-9 plays a marginal role in serum starvation-induced apoptosis.

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Institute of Cancer Research, Medical University of Vienna, 1090 Vienna, Austria.


Serum withdrawal represents a potent trigger to induce caspase-dependent apoptosis in a series of cell culture models. In rat 423-cells, caspase-8 and caspase-3 were apparently sufficient to initiate and proceed apoptosis without involving the intrinsic amplification loop via caspase-9. To assess the reasons for this inactivity of an otherwise crucial initiator caspase, we examined the ability for apoptosome assembly in 423-cells. Caspase-9 and Apaf-1 were expressed and cytochrome c released from mitochondria upon serum withdrawal. Although functional apoptosomes were assembled successfully in vitro, caspase-9 processing was found essentially refrained during apoptosis in 423-cells. Cell fractionation experiments revealed that sequestration of caspase-9 to cytoskeletal structures in 423-cells contributed to the observed impairment of apoptosome formation. Altogether, these findings provide evidence that serum starvation-induced apoptosis may occur independently of the intrinsic pathway and that caspase-9 sequestration potentially represents a novel biological antiapoptotic strategy.

[Indexed for MEDLINE]

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