Caspase-6

Caspase-6 (Cysteine-Requiring Aspartate Proteases) is part of a family of intracellular cysteine proteases that cleave their substrates after aspartic acid residues. These proteases play an integral role in inducing apoptosis in cells. Procaspase-6 (Mch2), a member of the ICE/ced-3 subfamily, is an inactive proenzyme that is activated to form caspase-6 by proteolytic cleavage at certain aspartic acid residues. During cleavage, the N-terminal is removed and the proenzyme is converted into a large (p18) and small (p11) subunits. Caspase-6 has two isoforms, ? and ?, produced by alternative splicing. Over-expression of the ? isoform of caspase-6 without its prodomain can induce apoptosis. The ? isoform does not seem to display proteolytic activity. Together with caspases-3 and -7, the ? isoform of caspase-6 is classified as an effector/execution caspase. Caspase-3, caspase-8 and caspase-10 can cleave procaspase-6. Active caspase-6 cleaves several other proteins such as lamins, NuMa and Keratin 18. A possible cleavage of caspases-8 and -10 in cytochrome-C dependent apoptosis was reported recently.