Mammalian cell death proteases: a family of highly conserved aspartate specific cysteine proteases.
So far nine human aspartate-specific cysteine proteases (ASCPs) have been identified and cloned in our lab and others. Their sequence and structural homology to the nematode Ced-3 implicated them in the cell death pathway of mammalian cells. Recent evidence suggests that ASCPs initiate apoptosis by acting at or near the cell death effector level. However, it is not clear whether the activity of one or several of these enzymes is necessary for execution of apoptosis. In addition, it is not yet clear how the proenzymes of ASCPs are activated or what triggers their activation. Execution of apoptosis in higher eukaryotes is apparently more complicated than in nematodes. It is most likely that in mammalian cells this process involves the coordinated action of multiple ASCPs and multiple redundant proteolytic pathways.
Alnemri
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Department of Biochemistry and Molecular Pharmacology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
D017398:Alternative Splicing; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001224:Aspartic Acid / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D020170:Caspase 1; D053455:Caspase 10; D053148:Caspase 3; D053178:Caspase 6; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D003001:Cloning, Molecular / Q000379:methods; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004789:Enzyme Activation; D005544:Forecasting; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008322:Mammals; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D001224:Aspartic Acid; C505407:CASP3 protein, human; C505514:CASP6 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053455:Caspase 10; D053148:Caspase 3; D053178:Caspase 6; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D003546:Cysteine Endopeptidases; C089223:ced-3 protein, C elegans; D020170:Caspase 1; C506438:CASP10 protein, human