Caspase-2: vestigial remnant or master regulator?
Caspase-2, the second mammalian caspase to be identified and the most evolutionarily conserved caspase, has eluded classification. The lack of a profound phenotype in the caspase-2-deficient mouse resulted in decreased interest in caspase-2 for many years. However, advances in the field, including the identification of a potential activation complex and the development of methods to detect active caspase-2, now illuminate our understanding of the function of this caspase. These studies suggest that caspase-2 induces death through two pathways. First, caspase-2 induces cell death independently of the mitochondrial pathway, in a manner similar to that of ced-3, a caspase in Caenorhabditis elegans. Second, caspase-2 also induces cell death upstream of the mitochondrial pathway. The choice of pathway may depend on the type of death stimulus. The placing of caspase-2 upstream and independent of mitochondrial dysfunction provides a potentially new therapeutic target for aberrant cell death.
Troy
Carol M
CM
Columbia University College of Physicians and Surgeons, Departments of Pathology and Neurology, Taub Center for the Study of Alzheimer's Disease and the Aging Brain, New York, NY 10032, USA. cmt2@columbia.edu
Ribe
Elena M
EM
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D017173:Caenorhabditis elegans / Q000166:cytology / Q000201:enzymology; D029742:Caenorhabditis elegans Proteins / Q000502:physiology; D053143:Caspase 2 / Q000235:genetics / Q000502:physiology*; D020169:Caspases / Q000502:physiology; D004789:Enzyme Activation; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000502:physiology; D015398:Signal Transduction
D029742:Caenorhabditis elegans Proteins; D053143:Caspase 2; D020169:Caspases; C089223:ced-3 protein, C elegans