fadd

Caspase-8 Protein, Human, Recombinant (His) is expressed in E. coli expression system with N-6xHis tag. The predicted molecular weight is 21.9 kDa and the accession number is Q14790.

CASR Protein, Human, Recombinant (GST) is expressed in E. coli expression system with N-GST tag. The predicted molecular weight is 93.6 kDa and the accession number is P41180.

Death domain-containing protein CRADD, also known as Caspase and RIP adapter with death domain, RIP-associated protein with a death domain, CRADD and RAIDD, is a protein which is constitutively expressed in most tissues, with particularly high expression in adult heart, testis, liver, skeletal muscle, fetal liver and kidney. CRADD RAIDD contains oneCARD domain and onedeath domain. CRADD RAIDD contains a death domain involved in the binding of RIP protein. The CARD domain mediates the interaction with caspase-2. FADD MORT1 is a death domain (DD)-containing adaptor signaling molecule that interacts with the intracellular DD of FAS APO-I ( CD95 ) and tumor necrosis factor receptor 1 and the prodomain of caspase-8 ( Mch5 MACH FLICE). CRADD RAIDD has a dual-domain structure similar to that of FADD. CRADD RAIDD has an NH2-terminal caspase homology domain that interacts with caspase-2 and a COOH-terminal DD that interacts with RIP. CRADD RAIDD could play a role in regulating apoptosis in mammalian cells. CRADD RAIDD is a apoptotic adaptor molecule specific for caspase-2 and FASL TNF receptor-interacting protein RIP. In the presence of RIP and TRADD, CRADD RAIDD recruits caspase-2 to the TNFR-1 signalling complex.

DR5, also called TRAIL R2, TRICK 2, TNFRSF10B, and MK is a type 1 TNF R superfamily, membrane protein which is a receptor for TRAIL (APO2 ligand). DR5 is a receptor for the cytotoxic ligand TNFSF10 TRAIL. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis.

Serine-threonine kinase which is a key regulator of TNF-mediated apoptosis, necroptosis and inflammatory pathways. Exhibits kinase activity-dependent functions that regulate cell death and kinase-independent scaffold functions regulating inflammatory signaling and cell survival. Has kinase-independent scaffold functions: upon binding of TNF to TNFR1, RIPK1 is recruited to the TNF-R1 signaling complex (TNF-RSC also known as complex I) where it acts as a scaffold protein promoting cell survival, in part, by activating the canonical NF-kappa-B pathway. Kinase activity is essential to regulate necroptosis and apoptosis, two parallel forms of cell death: upon activation of its protein kinase activity, regulates assembly of two death-inducing complexes, namely complex IIa (RIPK1-FADD-CASP8), which drives apoptosis, and the complex IIb (RIPK1-RIPK3-MLKL), which drives necroptosis. RIPK1 is required to limit CASP8-dependent TNFR1-induced apoptosis. In normal conditions, RIPK1 acts as an inhibitor of RIPK3-dependent necroptosis, a process mediated by RIPK3 component of complex IIb, which catalyzes phosphorylation of MLKL upon induction by ZBP1. Inhibits RIPK3-mediated necroptosis via FADD-mediated recruitment of CASP8, which cleaves RIPK1 and limits TNF-induced necroptosis. Required to inhibit apoptosis and necroptosis during embryonic development: acts by preventing the interaction of TRADD with FADD thereby limiting aberrant activation of CASP8. In addition to apoptosis and necroptosis, also involved in inflammatory response by promoting transcriptional production of pro-inflammatory cytokines, such as interleukin-6 (IL6). Phosphorylates RIPK3: RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation. Phosphorylates DAB2IP at 'Ser-728' in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade. Required for ZBP1-induced NF-kappa-B activation in response to DNA damage.

May play a role in the immune system processes. Protects cells from FAS-, TNF alpha- and FADD-induced apoptosis without increasing expression of the inhibitors of apoptosis BCL2 and BCLXL. Seems to activate an inhibitory pathway that prevents CASP8 activation following FAS stimulation, rather than blocking apoptotic signals downstream. May inhibit FAS-induced apoptosis by preventing CASP8 processing through CFLAR up-regulation.

Functions as key mediator in apoptosis and inflammation. Promotes caspase-mediated apoptosis involving predominantly caspase-8 and also caspase-9 in a probable cell type-specific manner. Involved in activation of the mitochondrial apoptotic pathway, promotes caspase-8-dependent proteolytic maturation of BID independently of FADD in certain cell types and also mediates mitochondrial translocation of BAX and activates BAX-dependent apoptosis coupled to activation of caspase-9, -2 and -3. Involved in macrophage pyroptosis, a caspase-1-dependent inflammatory form of cell death and is the major constituent of the ASC pyroptosome which forms upon potassium depletion and rapidly recruits and activates caspase-1. In innate immune response believed to act as an integral adapter in the assembly of the inflammasome which activates caspase-1 leading to processing and secretion of proinflammatory cytokines. The function as activating adapter in different types of inflammasomes is mediated by the pyrin and CARD domains and their homotypic interactions. Required for recruitment of caspase-1 to inflammasomes containing certain pattern recognition receptors, such as NLRP2, NLRP3, AIM2 and probably IFI16. In the NLRP1 and NLRC4 inflammasomes seems not be required but facilitates the processing of procaspase-1. In cooperation with NOD2 involved in an inflammasome activated by bacterial muramyl dipeptide leading to caspase-1 activation. May be involved in DDX58-triggered proinflammatory responses and inflammasome activation. In collaboration with AIM2 which detects cytosolic double-stranded DNA may also be involved in a caspase-1-independent cell death that involves caspase-8. In adaptive immunity may be involved in maturation of dendritic cells to stimulate T-cell immunity and in cytoskeletal rearrangements coupled to chemotaxis and antigen uptake may be involved in post-transcriptional regulation of the guanine nucleotide exchange factor DOCK2; the latter function is proposed to involve the nuclear form. Also involved in transcriptional activation of cytokines and chemokines independent of the inflammasome; this function may involve AP-1, NF-kappa-B, MAPK and caspase-8 signaling pathways. For regulation of NF-kappa-B activating and inhibiting functions have been reported. Modulates NF-kappa-B induction at the level of the IKK complex by inhibiting kinase activity of CHUK and IKBK. Proposed to compete with RIPK2 for association with CASP1 thereby down-regulating CASP1-mediated RIPK2-dependent NF-kappa-B activation and activating interleukin-1 beta processing. Modulates host resistance to DNA virus infection, probably by inducing the cleavage of and inactivating CGAS in presence of cytoplasmic double-stranded DNA.

Mouse Apoptosis-mediating surface antigen FAS (Fas) belongs to the death receptor subfamily of the TNF receptor superfamily and is designated TNFRSF6. Mouse Fas contains 1 death domain and 3 TNFR-Cys repeats. It detected in various tissues including thymus, liver, lung, heart, and adult ovary. As a receptor for TNFSF6 FASLG, The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases mediating apoptosis. FAS-mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen-stimulated suicide of mature T-cells, or both.

Nucleolar protein 3 is encoded by NOL3 gene. Multiple transcript variants encoding different isoforms have been found for this gene. So far, Nucleolar protein 3 has show to have two Isoforms. Isoform 1 may be involved in RNA splicing. Isoform 2 functions as an apoptosis repressor that blocks multiple modes of cell death. It inhibits extrinsic apoptotic pathways through two different ways. Firstly, it by interacting with FAS and FADD upon FAS activation blocking death-inducing signaling complex (DISC) assembly. Secondly by interacting with CASP8 in a mitochondria localization- and phosphorylation-dependent manner, limiting the amount of soluble CASP8 available for DISC-mediated activation. It has been shown to down-regulate the enzyme activities of caspase 2, caspase 8 and tumor protein p53.