Caspase-2 redux.
It has been difficult to assign caspase-2 to the effector or initiator caspase groups. It bears sequence homology to initiators (caspase-9 and CED-3), but its cleavage specificity is closer to the effectors (caspase-3 and -7). Interest in caspase-2 was dampened by the lack of a dramatic phenotype in the caspase-2 null mouse. Studies have been inhibited by the lack of knowledge about its mechanism of activation and the lack of specific methods to assay its activity. Molecular studies have defined a unique role for caspase-2 in apoptosis initiated by beta-amyloid toxicity or by trophic factor deprivation. Recently, a role for caspase-2 as an upstream initiator of mitochondrial permeabilization has been proposed. Thus, while much remains to be deciphered about caspase-2, most critically the mode of activation, it is clear that caspase-2 plays critical and singular roles in the control of programmed cell death.
Troy
C M
CM
Department of Pathology, Taub Institute for the Study of Alzheimer's Disease and the Aging Brain and the Center for Neurobiology and Behavior, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. cmt2@columbia.edu
Shelanski
M L
ML
D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053143:Caspase 2; D020169:Caspases / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000502:physiology; D006133:Growth Substances / Q000172:deficiency; D006801:Humans; D008928:Mitochondria / Q000201:enzymology; D009410:Nerve Degeneration / Q000201:enzymology; D015398:Signal Transduction / Q000502:physiology*
D016229:Amyloid beta-Peptides; D006133:Growth Substances; D053143:Caspase 2; D020169:Caspases