Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade

@article{Li1997CytochromeCA,
  title={Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade},
  author={Peng Li and Deepak Nijhawan and I. Imawati Budihardjo and Srinivasa M. Srinivasula and Manzoor Gatoo Ahmad and Emad S Alnemri and Xiaodong Wang},
  journal={Cell},
  year={1997},
  volume={91},
  pages={479-489}
}
We report here the purification of the third protein factor, Apaf-3, that participates in caspase-3 activation in vitro. [...] Key Result Apaf-3 was identified as a member of the caspase family, caspase-9. Caspase-9 and Apaf-1 bind to each other via their respective NH2-terminal CED-3 homologous domains in the presence of cytochrome c and dATP, an event that leads to caspase-9 activation. Activated caspase-9 in turn cleaves and activates caspase-3.Expand

Paper Mentions

Observational Clinical Trial
Cytochrome c is a mitochondrial protein that plays a key role in energy metabolism. When mitochondria are injured, cytochrome c may leave mitochondria and reach the bloodstream. The… Expand
ConditionsAccident, Blunt Injury, Blunt Trauma, (+2 more)
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References

SHOWING 1-10 OF 114 REFERENCES
DFF, a Heterodimeric Protein That Functions Downstream of Caspase-3 to Trigger DNA Fragmentation during Apoptosis
TLDR
A direct signal transduction pathway during apoptosis is delineated: caspase-3 to DFF to DNA fragmentation, which is a heterodimer of 40 kDa and 45 kDa subunits. Expand
CED-4—The Third Horseman of Apoptosis
A model for caspase activation is shown in Figure 1Figure 1. We still do not know precisely how BCL-2/CED-9-like proteins work. If they prevent apoptosis by blocking cytochrome c release, why wouldExpand
Affinity labeling displays the stepwise activation of ICE-related proteases by Fas, staurosporine, and CrmA-sensitive caspase-8
TLDR
Findings provide evidence that caspase-8, a CrmA-sensitive protease, is responsible for initiating the stepwise activation of multiple caspases in Fas-stimulated cells. Expand
Apaf-1, a Human Protein Homologous to C. elegans CED-4, Participates in Cytochrome c–Dependent Activation of Caspase-3
TLDR
The purification and cDNA cloning of Apaf-1, a novel 130 kd protein from HeLa cell cytosol that participates in the cytochrome c-dependent activation of caspase-3, leading to apoptosis is reported here. Expand
The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of Apoptosis
TLDR
In a cell-free apoptosis system, mitochondria spontaneously released cytochrome c, which activated DEVD-specific caspases, leading to fodrin cleavage and apoptotic nuclear morphology, and Bcl-2 acts to inhibit cy tochrome c translocation, thereby blocking caspase activation and the apoptotic process. Expand
Apopain/CPP32 cleaves proteins that are essential for cellular repair: a fundamental principle of apoptotic death
TLDR
The present studies demonstrate that U1-70kD and DNA-PKcs are excellent substrates for apopain, with cleavage occurring at sites that are highly similar to the cleavage site within PARP. Expand
Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis
TLDR
A potent peptide aldehyde inhibitor has been developed and shown to prevent apoptotic events in vitro, suggesting that apopain/CPP32 is important for the initiation of apoptotic cell death. Expand
Induction of Apoptotic Program in Cell-Free Extracts: Requirement for dATP and Cytochrome c
TLDR
Cells undergoing apoptosis in vivo showed increased release of cy tochrome c to their cytosol, suggesting that mitochondria may function in apoptosis by releasing cytochrome c. Expand
Overexpression of Bcl-X(L) inhibits Ara-C-induced mitochondrial loss of cytochrome c and other perturbations that activate the molecular cascade of apoptosis.
TLDR
Bcl-x(L) inhibits HIDAC-induced preapoptotic mitochondrial perturbations, which prevent the accumulation of cytochrome c in the cytosol, thereby preserving caspase-3 in the inactive zymogen state and checking the molecular cascade of apoptosis. Expand
The CED-3/ICE-like Protease Mch2 Is Activated during Apoptosis and Cleaves the Death Substrate Lamin A*
TLDR
It is shown that Mch2 is processed from its zymogen form to a proteolytically active dimeric species during execution of the apoptotic program and by the cytotoxic T cell death protease granzyme B. Expand
...
1
2
3
4
5
...