CASP8 Monoclonal Antibody

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Description

CASP8 Monoclonal Antibody: Structure and Function

CASP8 exists as a proenzyme (procaspase-8) and is activated during apoptosis or immune responses. Monoclonal antibodies targeting CASP8 detect both pro-forms (e.g., p55, p53) and cleaved active subunits (p43, p18/p10). These antibodies bind to epitopes on the pro-domain or catalytic subunits, enabling precise detection in experimental systems.

Key FeaturesDetails
Host speciesMouse or rat (e.g., clones 1H10, 90A992, 4G12)
IsotypesIgG (clones 1H10, 4G12) or IgM (clone C4106)
ReactivityHuman, rodent, non-human primates
Isoforms detectedProcaspase-8 (p55/p53), cleaved p43/p18/p10

Applications in Research

CASP8 antibodies are utilized in diverse experimental workflows:

Western Blotting (WB)

  • Protein detection: Procaspase-8 (55–53 kDa) and active subunits (p18/p10, p43) .

  • Optimal dilutions: 1–5 µg/mL for 1H10 , 1:300–5000 for 4G12 .

  • Controls: Jurkat cells (FAS-induced apoptosis) or recombinant CASP8 .

Immunohistochemistry (IHC)

  • Tissue analysis: Detects CASP8 in tumor samples or inflamed tissues .

  • Dilutions: 1:200–400 for IHC-P (paraffin sections) .

Flow Cytometry and ELISA

  • Reactivity: Clone 12F5 (IgG2b) detects procaspase-8 and active forms in human cells .

  • ELISA: Suitable for quantifying CASP8 in lysates or serum .

Role in Immune Regulation and Immunotherapy

CASP8 modulates PD-L1 expression, influencing tumor immune evasion:

  • Mechanism: CASP8 promotes A20-mediated ubiquitination and degradation of PD-L1, reducing immunosuppression .

  • Therapeutic relevance:

    • Low CASP8 expression in NK cells correlates with elevated PD-1/CTLA-4 and poor response to checkpoint inhibitors .

    • CASP8 knockdown in melanoma cells increases PD-L1 levels, sensitizing tumors to anti-PD-1/anti-CTLA-4 therapies .

Biomarker for Apoptosis and Cancer Therapy

  • Death receptor agonists: CASP8 expression predicts sensitivity to conatumumab (anti-DR5 antibody) in Ewing sarcoma (EWS). Overexpression of active CASP8 restores conatumumab efficacy in resistant EWS models .

  • Isoform-specific effects: Procaspase-8 isoforms (e.g., Caspase-8L) may interfere with apoptosis, impacting treatment outcomes .

Comparative Analysis of CASP8 Antibodies

CloneHostIsotypeReactivityApplicationsKey Features
1H10MouseIgGHumanWBDetects p55/p53/p43/p18; non-reducing WB
90A992MouseIgGHuman, NHP, chimpanzeeWB, IHC, FACSCross-reacts with non-human primates
4G12MouseIgGHuman, mouse, ratWB, IHC-PBroad reactivity; detects pro- and active forms
MAB704MouseIgGHumanWBDetects 55 kDa precursor and 42 kDa doublet
12F5MouseIgG2bHumanWB, IP, IHCRecognizes p55/p54 and p18 subunits

Therapeutic and Diagnostic Potential

  • Immunotherapy biomarkers: CASP8 expression levels may stratify patients for anti-PD-1/PD-L1 therapies .

  • Apoptosis modulation: Targeting CASP8 activation or inhibition could enhance therapeutic outcomes in cancers resistant to death receptor agonists .

Product Specs

Buffer
Phosphate-buffered saline (PBS), pH 7.4, containing 0.02% sodium azide as a preservative and 50% glycerol.
Form
Liquid
Lead Time
Typically, we can ship products within 1-3 business days after receiving your orders. Delivery times may vary depending on the purchasing method or location. Please consult your local distributors for specific delivery timeframes.
Synonyms
ALPS2B antibody; Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 12 protein antibody; Apoptosis related cysteine peptidase antibody; Apoptotic cysteine protease antibody; Apoptotic protease Mch-5 antibody; Apoptotic protease Mch5 antibody; CAP 4 antibody; CAP4 antibody; CASP-8 antibody; CASP8 antibody; CASP8_HUMAN antibody; Caspase 8 antibody; Caspase 8 apoptosis related cysteine peptidase antibody; Caspase IIX antibody; Caspase-8 subunit p10 antibody; caspase8 antibody; CED 3 antibody; FADD Homologous ICE/CED3 Like Protease antibody; FADD Like ICE antibody; FADD-homologous ICE/CED-3-like protease antibody; FADD-like ICE antibody; FLICE antibody; FLJ17672 antibody; ICE-like apoptotic protease 5 antibody; MACH alpha 1/2/3 protein antibody; MACH antibody; MACH beta 1/2/3/4 protein antibody; MACH5 antibody; MCH 5 antibody; MCH5 antibody; MGC78473 antibody; MORT1 associated ced 3 homolog antibody; MORT1 associated CED3 homolog antibody; MORT1-associated CED-3 homolog antibody; OTTHUMP00000163717 antibody; OTTHUMP00000163720 antibody; OTTHUMP00000163724 antibody; OTTHUMP00000163725 antibody; OTTHUMP00000165062 antibody; OTTHUMP00000165063 antibody; OTTHUMP00000165064 antibody; OTTHUMP00000206552 antibody; OTTHUMP00000206582 antibody
Target Names
Uniprot No.

Target Background

Function
Caspase-8 is a thiol protease that plays a crucial role in programmed cell death. It functions as a molecular switch for apoptosis, necroptosis, and pyroptosis, and is essential for preventing tissue damage during embryonic development and adulthood. As an initiator protease, it triggers extrinsic apoptosis by cleaving and activating effector caspases. These effector caspases are responsible for TNFRSF6/FAS-mediated and TNFRSF1A-induced cell death. Caspase-8 specifically cleaves and activates effector caspases CASP3, CASP4, CASP6, CASP7, CASP9, and CASP10. By binding to the adapter molecule FADD, caspase-8 recruits it to either TNFRSF6/FAS-mediated or TNFRSF1A receptor. The resulting aggregate, known as the death-inducing signaling complex (DISC), facilitates the proteolytic activation of CASP8. The active dimeric enzyme is subsequently liberated from the DISC and becomes free to activate downstream apoptotic proteases. Proteolytic fragments of the N-terminal propeptide, termed CAP3, CAP5, and CAP6, are likely retained within the DISC. Beyond extrinsic apoptosis, caspase-8 also acts as a negative regulator of necroptosis. It achieves this by cleaving RIPK1 at 'Asp-324', which is critical for inhibiting RIPK1 kinase activity, thus limiting TNF-induced apoptosis, necroptosis, and inflammatory responses. Caspase-8 can initiate pyroptosis by mediating the cleavage and activation of gasdermin-D (GSDMD). Cleavage of GSDMD promotes the release of the N-terminal moiety (Gasdermin-D, N-terminal), which binds to membranes and forms pores, triggering pyroptosis. It initiates pyroptosis following inactivation of MAP3K7/TAK1. Caspase-8 also functions as a regulator of innate immunity by mediating the cleavage and inactivation of N4BP1 downstream of TLR3 or TLR4, thereby promoting cytokine production. It may participate in the Granzyme B (GZMB) cell death pathways. Caspase-8 cleaves PARP1. Some isoforms lack the catalytic site and may interfere with the pro-apoptotic activity of the complex. These isoforms act as inhibitors of the caspase cascade.
Gene References Into Functions
  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. A 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. A 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 the 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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Database Links

HGNC: 1509

OMIM: 211980

KEGG: hsa:841

STRING: 9606.ENSP00000351273

UniGene: Hs.599762

Involvement In Disease
Caspase-8 deficiency (CASP8D)
Protein Families
Peptidase C14A family
Subcellular Location
Cytoplasm. Nucleus.
Tissue Specificity
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.

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