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PubMed · 11550085

Caspase-9 processing by caspase-3 via a feedback amplification loop in vivo.

E Fujita·J Egashira·K Urase·K Kuida·T Momoi
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Abstract

In contrast to the autoprocessing of caspase-9, little is known about the biological significance of caspase-9 processing by caspase-3 via a feedback loop in vivo. We prepared antisera against mouse caspase-9 cleavage sites so that only the activated form of mouse caspase-9 was recognized. Using these antisera and caspase-9- and caspase-3-deficient mouse embryonic fibroblasts, we demonstrated that mouse caspase-9 is initially autoprocessed at D(353) and D(368) at low levels during staurosporine-induced apoptosis, whereupon the D(368) and D(168) sites are preferentially processed over D(353) by activated caspase-3 as part of a feedback amplification loop. Ac-DEVD-MCA (caspase-3-like) and Ac-LEHD-MCA (caspase-9-like) cleavage activities clearly showed that caspase-9 autoprocessing was necessary for the activation of caspase-3, whereas full activation of caspase-3 and caspase-9 was achieved only through the feedback amplification loop. This feedback amplification loop also played a predominant role during programmed cell death of dorsal root ganglia neurons at mouse embryonic day 11.5.

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Amino Acid SequenceAnimalsAntibodiesAntibody SpecificityApoptosisCaspase 3Caspase 9CaspasesCells, CulturedEmbryo, MammalianEnzyme InhibitorsFibroblastsGanglia, SpinalImmunohistochemistryMiceMice, KnockoutMolecular Sequence DataStaurosporineJournal ArticleResearch Support, Non-U.S. Gov't

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E Fujita, J Egashira, K Urase, K Kuida, T Momoi. 2001. Caspase-9 processing by caspase-3 via a feedback amplification loop in vivo.. https://doi.org/10.1038/sj.cdd.4400824

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