Anti-Caspase-8 (Cleaved) Rabbit (Clone RM442)

Caspase-8 is an initiator caspase with roles in cell death, including induction of apoptosis and pyroptosis and inhibition of necroptosis. It is widely expressed during development and adulthood with high levels of expression in the heart and limb buds, as well as other tissues, in development and in leukocytes in adulthood. It localizes to the cytosol and can be found in the lamella of migrating cells. Caspase-8 is produced as an inactive proenzyme containing a prodomain, which is composed of two N-terminal death-effector domains (DEDs), and two C-terminal catalytic subunits: p18 and p10. Activation of the proenzyme occurs when it binds to the death-inducing signaling complex (DISC), which is composed of CD95, a Fas-associated death domain (FADD) protein, and cellular FLICE-like inhibitory protein (c-FLIP). Upon DISC binding, procaspase-8 is cleaved to release the p10 subunit, then the p18 subunit. Together, two of each subunit form an activated and stabilized heterotetramer, which cleaves other procaspases, including procaspase-3 and procaspase-7, to initiate the extrinsic apoptosis pathway. Caspase-8 also has a role in the innate immune response via its activation by toll-like receptor 4 (TLR4) signaling and its initiation of the pyroptosis pathway through the NOD-like receptor protein 3 (NLRP3) inflammasome. Mutations in CASP8, the gene encoding caspase-8, or dysfunctional caspase-8 activity are associated with a variety of conditions, including autoimmune disorders, immunodeficiencies, and an increased risk of cancer. Cayman's Caspase-8 (Cleaved) Rabbit Monoclonal Antibody (Clone RM442) be used for Western blot (WB).. Cross reactivity: (+) Human cleaved caspase-8: . (+) Human: .. Protein function: Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood. Initiator protease that induces extrinsic apoptosis by mediating cleavage and activation of effector caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death (PubMed:23516580, PubMed:8681376, PubMed:8681377, PubMed:9006941, PubMed:9184224, PubMed:8962078). Cleaves and activates effector caspases CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10 (PubMed:8962078, PubMed:9006941). Binding to the adapter molecule FADD recruits it to either receptor TNFRSF6/FAS mediated or TNFRSF1A (PubMed:8681376, PubMed:8681377). The resulting aggregate called death- inducing signaling complex (DISC) performs CASP8 proteolytic activation (PubMed:9184224). The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases (PubMed:9184224). Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC (PubMed:9184224). In addition to extrinsic apoptosis, also acts as a negative regulator of necroptosis: acts by cleaving RIPK1 at 'Asp-324', which is crucial to inhibit RIPK1 kinase activity, limiting TNF-induced apoptosis, necroptosis and inflammatory response (PubMed:31827280, PubMed:31827281). Also able to initiate pyroptosis by mediating cleavage and activation of gasdermin-D (GSDMD): GSDMD cleavage promoting release of the N-terminal moiety (Gasdermin-D, N-terminal) that binds to membranes and forms pores, triggering pyroptosis. Initiates pyroptosis following inactivation of MAP3K7/TAK1. Also acts as a regulator of innate immunity by mediating cleavage and inactivation of N4BP1 downstream of TLR3 or TLR4, thereby promoting cytokine production. May participate in the Granzyme B (GZMB) cell death pathways (PubMed:8755496). Cleaves PARP1 (PubMed:8681376). [The UniProt Consortium]