Journal ArticleDOI
The Caenorhabditis elegans cell death gene ced-4 encodes a novel protein and is expressed during the period of extensive programmed cell death
Junying Yuan,H. R. Horvitz +1 more
TLDR
Mutations in the gene ced-4 block almost all of the programmed cell deaths that normally occur during Caenorhabditis elegans development and two regions of the putative Ced-4 protein product show some similarity to known calcium-binding domains.Abstract:
Mutations in the gene ced-4 block almost all of the programmed cell deaths that normally occur during Caenorhabditis elegans development. We have cloned the ced-4 gene using a ced-4 mutation caused by the insertion of the transposon Tc4. When microinjected into a ced-4 animal, a 4.4 kb DNA fragment derived from the wild-type strain and corresponding to the region of the Tc4 insertion in the mutant ced-4(n1416) rescues the Ced-4 mutant phenotype. The ced-4 gene encodes a 2.2 kb RNA transcript. This mRNA is expressed primarily during embryogenesis, when most programmed cell deaths occur. The Ced-4 protein, as deduced from cDNA and genomic DNA clones, is 549 amino acids in length. Two regions of the putative Ced-4 protein product show some similarity to known calcium-binding domains.read more
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Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade
Peng Li,Deepak Nijhawan,Imawati Budihardjo,Srinivasa M. Srinivasula,Manzoor Ahmad,Emad S. Alnemri,Xiaodong Wang +6 more
TL;DR: Mutation of the active site of caspase-9 attenuated the activation of cazase-3 and cellular apoptotic response in vivo, indicating that casp enzyme-9 is the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and dATP.
Journal ArticleDOI
Cell Death: Critical Control Points
TL;DR: The identification of critical control points in the cell death pathway has yielded fundamental insights for basic biology, as well as provided rational targets for new therapeutics.
Journal ArticleDOI
Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition.
TL;DR: The identification of a novel protein, Smac, which promotes caspase activation in the cytochrome c/Apaf-1/caspase-9 pathway and increases cells' sensitivity to apoptotic stimuli is reported.
Journal ArticleDOI
Apaf-1, a Human Protein Homologous to C. elegans CED-4, Participates in Cytochrome c–Dependent Activation of Caspase-3
TL;DR: 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.
Journal ArticleDOI
Mechanisms and genes of cellular suicide
TL;DR: Genetic studies in the nematode Caenorhabditis elegans and in the fruit fly Drosophila melanogaster have led to the isolation of genes that are specifically required for the induction of programmed cell death.
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