CASPASES
Identification of Caspases as cell death proteins
First evidence for the involvement of cystein proteases in apoptosis
evolved when Horvitz et al. (Cell, vol. 75, pp641, 1993) reported
significant sequence similarity between the Caenorhabditis elegans
death gene ced-3 and the mammalian interleukin-1ß-converting enzyme
(ICE). In the nematode Caenorhabditis elegans, pathways of programmed
cell death were already intensively studied at this time. Among others,
the gene ced-3 was known to play an essential role in the initiation/execution
of the cell death program. Now it was suggested that the mammalian
ced-3 homolog ICE (known as the activator of the cytokine IL-1ß) could play
a key role in programmed cell death in vertebrates. This was confirmed by
the observation that overexpression of ICE induces apoptosis and that the
ICE inhibitors cow pox viral serpin CrmA and baculovirus p35 block ICE-induced
apoptosis. Following the identification of ICE as the mammalian counterpart
of the C. elegans death gene ced-3, nine other mammalian aspartate specific
cysteine proteases were identified and cloned. All those caspases
(as they are called now) show homology to ICE and Ced-3: this homology
was used in the identification/cloning of several of the caspase family
members (Alnemri, E.S., 1997, J. Cell. Biochem., 64: 33-42).