Human Caspase 8(Casp-8) ELISA Kit

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. Cleaves and activates effector caspases CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10. Binding to the adapter molecule FADD recruits it to either receptor TNFRSF6/FAS mediated or TNFRSF1A. The resulting aggregate called death-inducing signaling complex (DISC) performs CASP8 proteolytic activation. The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases. Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC. 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. 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. Cleaves PARP1.; Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex.; Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex.; Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex. Acts as an inhibitor of the caspase cascade.; Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex.

1. The caspase 8 mediated RIPK1 cleavage product has a pro-apoptotic function, and further cleavage of this pro-apoptotic cleavage product by human rhinovirus 3C protease may provide a mechanism by which human rhinovirus limits apoptosis. PMID: 29371673
2. results suggest that miR-21 regulates the apoptosis of keloid fibroblasts via targeting FasL, and caspase-8 and the mitochondria-mediated apoptotic signaling pathway is involved in this process. PMID: 29527928
3. neither rs13416436 nor rs2037815 associated with pre-eclampsia PMID: 28110598
4. High CASP8 expression is associated with Colorectal Cancer. PMID: 29801534
5. Sleep duration is associated with plasma caspase-8. Caspase-8 independently predicts diabetes mellitus years before disease onset and modifies the effect of sleep duration on incident diabetes mellitus. PMID: 29409058
6. Reactive oxygen species-induced cleavage of NHLRC2 by caspase-8 leads to apoptotic cell death in the HCT116 human colon cancer cells. PMID: 29242562
7. this study is the first report on reduced expression of CASP8 in breast cancer versus adjacent normal tissues. PMID: 29233452
8. The polymorphisms of CASP8, rs7608692, and haplotype AGAACAG correlated with neutropenia toxicity. The haplotype GGGGAAA was associated with thrombocytopenia toxicity. We conclude that the polymorphisms of CASP8 contribute to the prognosis of advanced lung adenocarcinoma and influence the quality of life and survival. PMID: 28278082
9. These results indicated that cMyc and Fas regulated the sensitivity of A549 cells to irradiation by regulating caspase8-mediated Bid activation and the subsequent association with the mitochondrial pathway of apoptosis. PMID: 28849062
10. miR-21 was elevated in osteosarcoma, and overexpression of miR-21 suppressed apoptosis via targeting caspase 8. PMID: 28109080
11. Our findings indicate the relationship of SNP CASP8 D302H and breast cancer would not be universal but only be sensitive in some particular European countries. PMID: 28674227
12. no mutations were detected in the CASP8 gene, but we observed a frequent [32/48 (66.6%)] SNP [rs1045487] in the oral cancer samples. PMID: 28181739
13. case-control study, including 600 hepatocellular carcinoma (HCC) and 600 HBsAg positive controls without HCC, was conducted to assess the relationship between 11 tagging SNPs in CASP8, CASP10 and CFLAR and HBV-related HCC risk .These results suggest that the CASP8 -652 6N ins/del polymorphism may play a protective role in the development, progression, and survival of HBV-related HCC among the Chinese Han population. PMID: 28643196
14. High caspase-8 is not significantly associated with adverse breast cancer-specific survival. No associations were observed between caspase-8 and clinicopathological criteria. PMID: 27798717
15. we found that plumbagin could enhance TRAIL-induced apoptosis in Kasumi-1 cells, and the mechanisms include ROS-mediated upregulation of DR5 expression, caspase-8 activation and inhibition of cFLIP expression PMID: 28498435
16. this study shows that mitochondrial DNA oxidation induces imbalanced activity of NLRP3/NLRP6 inflammasomes by activation of caspase-8 and BRCC36 in dry eye PMID: 28238526
17. Importantly, the bioinformatics analysis of microarray gene expression data derived from a set of high-grade human gliomas, shows that high Caspase-8 expression levels correlate with a worse prognosis. PMID: 28594322
18. this review describes the role of caspase-8 in the initiation of extrinsic apoptosis execution and the mechanism by which caspase-8 inhibits necroptosis PMID: 28462525
19. Data indicate that elevated levels of Polo-like kinase 3 (Plk3)and pT273 caspase-8 are correlated with favorable clinical outcome in patients with anal squamous cell carcinoma (anal SCC) treated with concomitant chemoradiotherapy (CRT). PMID: 27462786
20. Caspase-8 binding via FADD to the receptor is an indispensable initiating step in death-inducing signaling complex formation and NF-kB activation. PMID: 28445729
21. The procaspase-8 Q482H mutation in AML patients abolishes caspase-8-mediated apoptosis by impairing procaspase-8 dimerization. PMID: 29191655
22. These findings suggest that intracellular cholesterol level affects TMZ treatment of GBM mediated via a DR5-caspase-8 mechanism. PMID: 29162448
23. study shows genetic association of rare variants in CASP8 with Alzheimer's disease and proposes a mechanism of action mediated by decreased enzyme activity; for two CASP8 variants, p.K148R and p.I298V, the association remained significant in a large combined sample PMID: 28985224
24. Knockout (KO) or knockdown of caspase-8, CD95 or FADD prevents activation of Plk3 upon CD95 stimulation, suggesting a requirement of a functional death-inducing signaling complex for Plk3 activation. PMID: 27325299
25. SP-D increases the formation of nuclear and membrane blebs. Inhibition of caspase-8 confirms the effect of SP-D is unique to the caspase-8 pathway. PMID: 29107869
26. Results illustrate the temporal and spatial activation of caspase-8 and -3 in microglia/macrophages occurring upon ischemic stroke and suggest that the expression of these caspases could be used in neuropathological diagnostic work. PMID: 27566702
27. This is the first report, showing negative and independent prognostic impact of the CASP8 -652 6N Del and the 302His variant for breast cancer. PMID: 27507139
28. Data suggest that pro-death signals through TIR-domain-containing adapter-inducing interferon-beta (TRIF) are regulated by autophagy and propose that pro-apoptotic signalling through TRIF/RIPK1/caspase-8 occurs in fibrillary platforms. PMID: 28453927
29. caspase-8-dependent apoptosis was linked to hepatocellular carcinoma development. PMID: 28898696
30. Insertion genotype of CASP8 rs3834129 polymorphisms showed risk in CAD. CASP8 rs3769818 activates intronic cryptic donor. PMID: 28633917
31. Caspase-8 controls the secretion of inflammatory lysyl-tRNA synthetase in exosomes from colorectal cancer cells. PMID: 28611052
32. Fisetin inhibited Triple-Negative Breast Cancer Cells cell division and induced apoptosis, which was associated with mitochondrial membrane permeabilization and the activation of caspase-9 and caspase-8, as well as the cleavage of poly(ADP-ribose) polymerase-1. PMID: 26755433
33. Caspase-8 can serve in two distinct roles in response to TRAIL receptor engagement, as a scaffold for assembly of a Caspase-8-FADD-RIPK1 "FADDosome" complex, leading to NFkappaB-dependent inflammation, or as a protease that promotes apoptosis. PMID: 28212752
34. Using the tDED filament structure as a template, structural analyses reveal the interaction surfaces between FADD and caspase-8 and the distinct mechanisms of regulation by cFLIP and MC159 through comingling and capping, respectively. PMID: 27746017
35. our novel findings expand our understanding of the key mechanisms underlying the anti-apoptotic functions of caspase-8 which may act as a critical block to existing antitumour therapies. PMID: 27109099
36. Dasatinib, a c-Src inhibitor, dephosphorylated caspase-8 to facilitate necroptosis, rather than apoptosis, in paclitaxel-treated p-Casp8-expressing lung adenocarcinoma cells. PMID: 27195913
37. Loss of function mutations in FAT1 and CASP8 prevent cell adhesion and promote cell migration and proliferation in oral squamous cell carcinoma cell lines. PMID: 27693639
38. Dysregulation of a potassium channel, THIK-1, targeted by caspase-8, accelerates cell shrinkage. PMID: 27566292
39. caspase-8 and caspase-9 contribute to the cyclic stretch-induced apoptosis, but functioned differently at different stages in human periodontal ligament cells PMID: 27942018
40. Down-regulation of mRNA expression was found in cases in which CASP8, TMS1 and DAPK were hypermethylated. PMID: 28361856
41. sorafenib overcomes TRAIL resistance in renal cell carcinoma by a mechanism that does not rely on Mcl-1 down-regulation but involves ROS accumulation and increased activation of caspase-8 PMID: 28154184
42. autoinflammation-associated H443P nlrc4 mutant is altered in interaction with SUG1 and ubiquitinated proteins, triggering constitutive caspase-8-mediated cell death dependent on FADD but independent of Ser(533) phosphorylation. PMID: 27974463
43. Caspase-8 is phosphorylated on Tyr380 in a Src kinase dependent manner and this phosphorylation is required for transformation and it is enhanced by hypoxic conditions. PMID: 27432652
44. Our results revealed that caspase-8 gene silencing may result from the methylation of its gene promoter in human glioma tissues. The expression of caspase-8 at the mRNA level was significantly associated with the grade of human glioma. PMID: 28204824
45. Suggest that caspase 8 SNPs were not associated with rheumatoid arthritis. PMID: 26905515
46. novel dynamic interplay between Src and caspase-8 likely acts as a potent signal-integrating switch directing the cell towards apoptosis or survival PMID: 27101103
47. Findings showed that, in MDA-MB-231 cells, casp-8 might play some unusual roles which should be better explored, in order to understand whether it might be identified as a molecular therapeutic target. PMID: 27082853
48. Study showed that TRAIL and caspase-8 expression decreased in human osteosarcoma, resulting in increased cell proliferation, and reduced cell apoptosis suggesting they play important roles in the occurrence, development, and prognosis of osteosarcoma. PMID: 28002586
49. evidence that Articulatin-D efficiently activates caspase-8 involved in extrinsic pathway of apoptosis induction, which ultimately results in caspase-3-dependent DNA fragmentation of Jurkat cells. PMID: 27868169
50. our findings indicate that the expression levels of P-GP, MYC, caspase-8, and AKT3 are candidate biomarkers of cell sensitivity to PLKis. PMID: 27699933

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Caspase-8 deficiency (CASP8D)

Cytoplasm. Nucleus.

Peptidase C14A family

Isoform 1, isoform 5 and isoform 7 are expressed in a wide variety of tissues. Highest expression in peripheral blood leukocytes, spleen, thymus and liver. Barely detectable in brain, testis and skeletal muscle.

HGNC: 1509

OMIM: 211980

KEGG: hsa:841

STRING: 9606.ENSP00000351273

UniGene: Hs.599762