Recombinant Human Caspase-10 (Mch 4) Protein, CF

Caspase-10 (also known as Mch4 and FLICE2) is a 28‑29 kDa member of the peptidase C14A family of enzymes (1‑4). It is widely expressed, being found in dendritic cells, T and B cells, neurons, keratinocytes, and intestinal epithelium (5‑8). Caspase-10 appears to be an initiator caspase, and is known to act on a select number of substrates, including Bid, ABCF1, AKAP1, PARP, HSP90 beta and procaspases-3, 4, 6, 7, and 9 (1, 2, 9‑12). There are several alternatively spliced forms of human Caspase‑10, and all forms contains the same pro region (aa 1‑219) with two death effector domains (DEDs) (SwissProt # Q92851). Recombinant Human Caspase-10 (Mch4) corresponds to the mature region of isoform B and is based on the sequence described by Fernandes‑Alnemri et al. (4). Normally, procaspase‑10 is an inactive, cytosolic monomer (2, 9). But following DED containing receptor trimerization, procaspase‑10 is recruited to a complex termed DISC that forms around the death domains of the oligomerized receptor (1, 2, 9, 13). FADD is recruited first, followed by both procaspase‑10 and 8. The recruitment, or concentration, of both procaspase‑8 and ‑10 induces their homodimerization and activation. The actual activation of Caspase‑10 can occur either through homodimerization and self‑cleavage, or caspase‑8‑induced cleavage (9, 11, 12). Cleavage initially generates a 43 kDa (p43) N‑terminal and an 12 kDa (p12) C‑terminal fragment. The p43 subunit is next cleaved at Asp219‑Val220 to generate a 25 kDa (p25) DED‑containing prodomain and a 17 kDa mature p17 subunit (14). p17 and p12 noncovalently associate to form a 29 kDa heterodimer, which subsequently associates with another p17/p12 heterodimer to form an active, mature Caspase-10 molecule. This leaves the DISC to act on downstream substrates. There does not appear to be a mouse gene equivalent to the human CASP10 gene (15).