Table; caspase-1 ,-2 ,-3 ,-4 ,-5 ,-6 ,-7 ,-8 ,-9 ,-10



By substraction cloning a set of mouse genes (named Nedd1 through Nedd10) with developmentally down-regulated expression in brain was identified. One of these genes, Nedd2, encodes a protein similar to the mammalian interleukin-1b -converting enzyme (ICE) and the product of the Caenorhabditis elegans cell death gene ced-3 (CED-3). Overexpression of Nedd2, renamed caspase-2, in cultured fibroblast and neuroblastoma cells also resulted in cell death by apoptosis, which was suppressed by the expression of the human bcl-2 gene, indicating that Nedd2 is functionally similar to the ced-3 gene in C. elegans. (Kumar et al., 1994). Using a murine Nedd2 cDNA, a human foetal brain cDNA library was screened at low stringency, and Ich-1, the human homologue of Nedd2, was identified (Wang et al., 1994).


The cleavage of caspase-2 to its catalytically active subunits during apoptosis was demonstrated by MacFarlane in the human monocytic tumour cell line THP.1 (MacFarlane et al., 1997). In cells exposed to an apoptotic stimulus, some processing of caspase-2 was detected in morphologically normal cells, suggesting that cleavage of caspase-2 may occur early in the apoptotic process. Caspase-2 was also shown to undergo alternative splicing which results in two distinct caspase-2 mRNA species. One mRNA species encodes a protein product of 435 amino acids (caspase-2L) that is homologous to both the p20 and p10 subunits of ICE (27% identity) and the entire CED-3 protein (28% identity). The other mRNA encodes a 312 amino acid truncated version of caspase-2 protein (caspase-2S). Overexpression of caspase-2L induces programmed cell death, suggesting that caspase-2 is also a mammalian programmed cell death gene. More interestingly, overexpression of the caspase-2S suppresses Rat-1 cell death induced by serum deprivation. These observations suggest that caspase-2 plays an important role in both positive and negative regulation of programmed cell death in vertebrate animals (Wang et al., 1994). To date, there are no substrates known for caspase-2.