Specific Ablation of the Apoptotic Functions of Cytochrome c Reveals a Differential Requirement for Cytochrome c and Apaf-1 in Apoptosis

@article{Hao2005SpecificAO,
  title={Specific Ablation of the Apoptotic Functions of Cytochrome c Reveals a Differential Requirement for Cytochrome c and Apaf-1 in Apoptosis},
  author={Zhenyue Hao and Gordon S. Duncan and Chia-Che Chang and Andrew J. Elia and Min Fang and Andrew C Wakeham and Hitoshi Okada and Thomas Calzascia and YingJu Jang and Annick Itie You-Ten and Wen-Chen Yeh and Pamela S. Ohashi and Xiaodong Wang and Tak Wah Mak},
  journal={Cell},
  year={2005},
  volume={121},
  pages={579-591}
}
As components of the apoptosome, a caspase-activating complex, cytochrome c (Cyt c) and Apaf-1 are thought to play critical roles during apoptosis. Due to the obligate function of Cyt c in electron transport, its requirement for apoptosis in animals has been difficult to establish. We generated "knockin" mice expressing a mutant Cyt c (KA allele), which retains normal electron transfer function but fails to activate Apaf-1. Most KA/KA mice displayed embryonic or perinatal lethality caused by… 
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References

SHOWING 1-10 OF 60 REFERENCES
Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes.
TLDR
Examination of the role of CPP32 in apoptosis using mice, embryonic stem cells, and mouse embryonic fibroblasts deficient for the caspase indicates that CPP 32 is an essential component in apoptotic events that is remarkably system- and stimulus-dependent.
Apaf1 Is Required for Mitochondrial Pathways of Apoptosis and Brain Development
TLDR
Data indicate that Apaf1 plays a central role in the common events of mitochondria-dependent apoptosis in most death pathways and that this role is critical for normal development.
Determinants of Cytochrome c Pro-apoptotic Activity
TLDR
Whether the inactivity of the yeast isoforms is related to a post-translational modification of lysine 72,N-ε-trimethylation is examined, which was found to abrogate pro-apoptotic activity of metazoan cytochrome cexpressed in yeast.
Differential Requirement for Caspase 9 in Apoptotic Pathways In Vivo
TLDR
Comparison of the requirement for Casp9 and Casp3 in different apoptotic settings indicates the existence of at least four different apoptosis pathways in mammalian cells.
Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice
TLDR
CPP32 is shown to play a critical role during morphogenetic cell death in the mammalian brain during embryonic day 12, resulting in a variety of hyperplasias and disorganized cell deployment.
Adult Apaf-1-deficient mice exhibit male infertility.
TLDR
Cytochrome c-mediated apoptosis is not absolutely required for normal neural development, but is essential for spermatogenesis, and these findings strongly suggest that alternative apoptotic pathways work in conjunction with and parallel to Apaf-1 and can modify its effect on programmed cell death.
Cytochrome c Deficiency Causes Embryonic Lethality and Attenuates Stress-Induced Apoptosis
TLDR
The role of cytochrome c is defined as an essential component of an apoptotic pathway responsive to DNA damage and other forms of cell stress and cells lacking cy tochrome c demonstrate increased sensitivity to cell death signals triggered by TNFalpha.
Apaf1 (CED-4 Homolog) Regulates Programmed Cell Death in Mammalian Development
TLDR
It is suggested that Apaf1 is essential for Casp3 activation in embryonic brain and is a key regulator of developmental programmed cell death in mammals.
Apoptosis initiated by Bcl-2-regulated caspase activation independently of the cytochrome c/Apaf-1/caspase-9 apoptosome
TLDR
It is concluded that Bcl-2 regulates a caspase activation programme independently of the cytochrome c/Apaf-1/caspase-9 ‘apoptosome’, which seems to amplify rather than initiate the casp enzyme cascade.
Reduced Apoptosis and Cytochrome c–Mediated Caspase Activation in Mice Lacking Caspase 9
TLDR
Results indicate that Casp9 is a critical upstream activator of the caspase cascade in vivo, as indicated by the absence of Casp3-like cleavage and the restoration of cytochrome c-mediated cleavage after addition of in vitro-translated Casp 9.
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5
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