High impact information on CASP7

• These observations suggest that CPP32 and Mch3 are targets of mature Mch4 protease in apoptotic cells [1].
• We call this enzyme Mch3/SCA-2 [2].
• We have purified from hamster liver a second cysteine protease that cleaves and activates sterol regulatory element binding proteins (SREBPs). cDNA cloning revealed that this enzyme is the hamster equivalent of Mch3, a human enzyme that is related to the interleukin 1beta converting enzyme [2].
• Mch3, a novel human apoptotic cysteine protease highly related to CPP32 [3].
• Here we report the cloning of a new Ced-3/interleukin 1 beta-converting enzyme-related gene, designated Mch3, that encodes a protein with the highest degree of homology to CPP32 compared to other family members [3].

Biological context of CASP7

• It was of interest that recombinant CPP32-p17 subunit can form an active heteromeric enzyme complex with recombinant Mch3 alpha-p12 subunit and vice versa, as determined by the ability of the heteromeric complexes to induce apoptosis in Sf9 cells [3].
• Importantly, upon receipt of a death stimulus, endogenous ICE-LAP3 is processed to its subunit forms, suggesting a physiological role in cell death [4].
• We have identified and characterized a novel cysteine protease named CMH-1 that is a new member of the interleukin 1 beta converting enzyme (ICE) family of proteases with substrate specificity for Asp-X [5].
• Only 1 of the 18 SNPs in CASP7 (SNP144692) differed significantly in frequency in the haplotypes found in affected individuals compared to control Bedouin haplotypes [6].
• CPP32 was assigned to chromosome 4q33-q35.1, Mch2 to chromosome 4q25-q26, Mch3 to chromosome 10q25.1-q25.2 and Ich-1 to chromosome 7q35 [7].

Anatomical context of CASP7

• Importantly, Jurkat T cells incubated with granzyme B and a sublytic concentration of perforin undergo apoptosis, which is preceded by the activation of endogenous ICE-LAP3 [8].
• Pro-ICE-LAP3 is a 35-kDa protein localized to the cytoplasm and expressed in a variety of tissues and cell lines [4].
• Overexpression of CMH-1 in COS cells resulted in the processing of CMH-1 and the induction of apoptosis of transfected cells [5].

Associations of CASP7 with chemical compounds

• CMH-1 shares conserved amino acid residues that form the core structure of ICE as well as those residues involved in catalysis and in the P1 aspartate binding [5].
• In Jurkat T cells, Fas ligation or addition of exogenous C2-ceramide induced activations of caspase-3/CPP32 and caspase-7/Mch3 followed by PARP cleavage, effects that can be blocked either by SPP or TPA [9].

Enzymatic interactions of CASP7

• Purified recombinant CMH-1 cleaved PARP but not interleukin 1 beta precursor in vitro [5].

Regulatory relationships of CASP7

• Cytotoxic T-cell-derived granzyme B activates the apoptotic protease ICE-LAP3 [8].

Other interactions of CASP7

• Here we report the chromosomal mapping of CPP32 to 4q34, MCH2 to 4q25, and MCH3 to 10q25 [10].
• Caspase 7 (CASP7), an apoptosis-related cysteine protease, is one of the few known genes in this region [6].

Analytical, diagnostic and therapeutic context of CASP7

• In this paper the chromosomal localization of the human genes CPP32, Mch2, Mch3 and Ich-1 is reported, obtained by Radiation Hybrid Mapping [7].

References