Caspase-8/FADD-like ICE (FLICE), is an ~55 kDa cytosolic protein belonging to the Fas/APO-1/CD95 death-inducing signaling complex. Although researchers have defined eight different isoforms of caspase-8 at the mRNA level (8/a-h), significant expression of only Caspase-8/a and /b occurs at the protein level in a variety of cell lines. Caspase-8 contains two death effector domains (DEDs) and exhibits sequence homology to both FADD, a signal transducer of Fas-induced apoptosis, and to the ICE/CED-3 family of cysteine proteases. Caspase-8 binds to FADD through its amino terminal DEDs and induces apoptosis when overexpressed. Activation of Caspase-8 involves a two-step proteolysis whereby the cleavage of Caspase-8 generates a 43 kDa fragment (p43) and a 12 kDa fragment further processed to 10 kDa, then the cleavage of receptor-associated p43 yields p26 and the release of the active site containing p18. A number of cytosolic factors inhibit the FADD-Caspase-8 containing signaling complex, including the ICE/CED-3 family inhibitor CrmA which inhibits Caspase-8 protease activity, and the short and long forms of FLIP that bind to the FADD-Caspase-8 complex.
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Regulatory Status |
RUO – Research Use Only |
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