caspase 8


Summary: A long pro-domain caspase that contains a death effector domain in its pro-domain region. Caspase 8 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS.

Top Publications

  1. Teitz T, Wei T, Valentine M, Vanin E, Grenet J, Valentine V, et al. Caspase 8 is deleted or silenced preferentially in childhood neuroblastomas with amplification of MYCN. Nat Med. 2000;6:529-35 pubmed
    b>Caspase 8 is a cysteine protease regulated in both a death-receptor-dependent and -independent manner during apoptosis...
  2. Guida N, Laudati G, Serani A, Mascolo L, Molinaro P, Montuori P, et al. The neurotoxicant PCB-95 by increasing the neuronal transcriptional repressor REST down-regulates caspase-8 and increases Ripk1, Ripk3 and MLKL expression determining necroptotic neuronal death. Biochem Pharmacol. 2017;142:229-241 pubmed publisher
    ..In addition, since REST is involved in several neurological disorders, therapies that block REST-induced necroptosis could be a new strategy to revert the neurodetrimental effects associated to its overexpression. ..
  3. Sampath R, Cummins N, Natesampillai S, Bren G, Chung T, Baker J, et al. Increasing procaspase 8 expression using repurposed drugs to induce HIV infected cell death in ex vivo patient cells. PLoS ONE. 2017;12:e0179327 pubmed publisher
    ..Future studies will be required to define the clinical utility of this or similar approaches. ..
  4. Mañas A, Wang S, Nelson A, Li J, Zhao Y, Zhang H, et al. The functional domains for Bax∆2 aggregate-mediated caspase 8-dependent cell death. Exp Cell Res. 2017;359:342-355 pubmed publisher
    ..Instead, it forms cytosolic aggregates and activates caspase 8. However, the functional domain(s) responsible for BaxΔ2 behavior have remained elusive...
  5. Adaramoye O, Erguen B, Nitzsche B, Hopfner M, Jung K, Rabien A. Punicalagin, a polyphenol from pomegranate fruit, induces growth inhibition and apoptosis in human PC-3 and LNCaP cells. Chem Biol Interact. 2017;274:100-106 pubmed publisher
    ..Moreso, PN increased the expressions of caspases-3 and -8 in PC-3. Overall, PN exerts anti-proliferative activity in PCa cells via induction of apoptosis and anti-angiogenic effect. ..
  6. Dong X, Fu J, Yin X, Qu C, Yang C, He H, et al. Induction of Apoptosis in HepaRG Cell Line by Aloe-Emodin through Generation of Reactive Oxygen Species and the Mitochondrial Pathway. Cell Physiol Biochem. 2017;42:685-696 pubmed publisher
    ..These findings underscore the need for risk assessment of human exposure to aloe-emodin. ..
  7. Wu J, Ding M, Mao N, Wu Y, Wang C, Yuan J, et al. Celastrol inhibits chondrosarcoma proliferation, migration and invasion through suppression CIP2A/c-MYC signaling pathway. J Pharmacol Sci. 2017;134:22-28 pubmed publisher
    ..To sum up, we found that celastrol had effects on inhibiting proliferation, migration, invasion and inducing apoptosis through suppression CIP2A/c-MYC signaling pathway in vitro, which may provide a new therapeutic regimen for CS. ..
  8. He G, Günther C, Thonn V, Yu Y, Martini E, Buchen B, et al. Regression of apoptosis-resistant colorectal tumors by induction of necroptosis in mice. J Exp Med. 2017;214:1655-1662 pubmed publisher
  9. Kischkel F, Lawrence D, Chuntharapai A, Schow P, Kim K, Ashkenazi A. Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5. Immunity. 2000;12:611-20 pubmed
    ..TRADD and RIP, which bound TNFR1, did not bind DR4 and DR5. Thus, Apo2L/TRAIL and FasL initiate apoptosis through similar mechanisms, and FADD may be a universal adaptor for death receptors. ..

More Information


  1. Ha H, Park H. Molecular basis for the effect of the L31F mutation on CARD function in ARC. FEBS Lett. 2017;591:2919-2928 pubmed publisher
    ..In addition, the L31F mutation disrupts homodimer formation that is critical to ARC functions. Our current study reveals the molecular basis for the L31F mutation disrupting the ARC CARD functions. ..
  2. Zhang H, Zhou F, Pan Z, Bu X, Wang Y, Chen F. 11?-hydroxysteroid dehydrogenases-2 decreases the apoptosis of MC3T3/MLO-Y4 cells induced by glucocorticoids. Biochem Biophys Res Commun. 2017;490:1399-1406 pubmed publisher
    ..In our study, we concluded that 11?-HSD-2 plays an important role in the development of bone or osteoblast cell apoptosis, and the decreased expression of 11?-HSD-2 may aggravate steroid induced bone/osteoblast cell apoptosis. ..
  3. Henry C, Martin S. Caspase-8 Acts in a Non-enzymatic Role as a Scaffold for Assembly of a Pro-inflammatory "FADDosome" Complex upon TRAIL Stimulation. Mol Cell. 2017;65:715-729.e5 pubmed publisher
  4. Jaco I, Annibaldi A, Lalaoui N, Wilson R, Tenev T, Laurien L, et al. MK2 Phosphorylates RIPK1 to Prevent TNF-Induced Cell Death. Mol Cell. 2017;66:698-710.e5 pubmed publisher
    ..Thus, MK2-mediated phosphorylation of RIPK1 serves as a checkpoint within the TNF signaling pathway that integrates cell survival and cytokine production. ..
  5. Du X, Liu X, Wang Z, Wang Y. SLPI promotes the gastric cancer growth and metastasis by regulating the expression of P53, Bcl-2 and Caspase-8. Eur Rev Med Pharmacol Sci. 2017;21:1495-1501 pubmed
    ..We concluded that SLPI was closely related with to invasion and metastasis of gastric cancer. Perhaps we can hopefully find new targets for the treatment of gastric cancer. ..
  6. Gentle I, McHenry K, Weber A, Metz A, Kretz O, Porter D, et al. TIR-domain-containing adapter-inducing interferon-β (TRIF) forms filamentous structures, whose pro-apoptotic signalling is terminated by autophagy. FEBS J. 2017;284:1987-2003 pubmed publisher
    ..We conclude that pro-death signals through TRIF are regulated by autophagy and propose that pro-apoptotic signalling through TRIF/RIPK1/caspase-8 occurs in fibrillary platforms. ..
  7. MacFarlane M, Merrison W, Dinsdale D, Cohen G. Active caspases and cleaved cytokeratins are sequestered into cytoplasmic inclusions in TRAIL-induced apoptosis. J Cell Biol. 2000;148:1239-54 pubmed
    ..We propose that effector caspase-mediated cleavage of cytokeratins, resulting in disassembly of the cytoskeleton and formation of cytoplasmic inclusions, may be a characteristic feature of epithelial cell apoptosis. ..
  8. Gundapaneni K, Shyamala N, Galimudi R, Kupsal K, Gantala S, Padala C, et al. Polymorphic variants of Caspase genes (8 & 3) in the risk prediction of Coronary Artery Disease. Gene. 2017;627:278-283 pubmed publisher
    ..The aim of the present study is to examine the role of Caspase 8 and 3 polymorphisms in the pathogenesis of CAD...
  9. Rehker J, Rodhe J, Nesbitt R, Boyle E, Martin B, Lord J, et al. Caspase-8, association with Alzheimer's Disease and functional analysis of rare variants. PLoS ONE. 2017;12:e0185777 pubmed publisher
  10. Nikbakht M, Jha A, Malekzadeh K, Askari M, Mohammadi S, Marwaha R, et al. Aberrant promoter hypermethylation of selected apoptotic genes in childhood acute lymphoblastic leukemia among North Indian population. Exp Oncol. 2017;39:57-64 pubmed
    ..This abnormality occurs in leukemogenesis and it may be used as a biomarker and for predicting the prognosis of ALL. ..
  11. Sadek N, Yuliana N, Prangdimurti E, Priosoeryanto B, Budijanto S. Plant Sterol Esters in Extruded Food Model Inhibits Colon Carcinogenesis by Suppressing Inflammation and Stimulating Apoptosis. J Med Food. 2017;20:659-666 pubmed publisher
    ..The proposed mechanisms are by suppressing inflammation and inducing apoptosis...
  12. Kim M, Hernandez L, Annunziata C. Caspase 8 expression may determine the survival of women with ovarian cancer. Cell Death Dis. 2016;7:e2045 pubmed publisher
  13. Wang C, He H, Dou G, Li J, Zhang X, Jiang M, et al. Ginsenoside 20(S)-Rh2 Induces Apoptosis and Differentiation of Acute Myeloid Leukemia Cells: Role of Orphan Nuclear Receptor Nur77. J Agric Food Chem. 2017;65:7687-7697 pubmed publisher
    ..orphan nuclear receptor Nur77 and death receptor proteins Fas, FasL, DR5, and TRAIL, as well as the cleavage of caspase 8 and caspase 3 in HL-60 cells...
  14. Faleiro L, Lazebnik Y. Caspases disrupt the nuclear-cytoplasmic barrier. J Cell Biol. 2000;151:951-9 pubmed
    ..Hence, caspase-9 contributes to cell disassembly by disrupting the nuclear cytoplasmic barrier. ..
  15. Mazzeo A, Arroba A, Beltramo E, Valverde A, Porta M. Somatostatin protects human retinal pericytes from inflammation mediated by microglia. Exp Eye Res. 2017;164:46-54 pubmed publisher
    ..These results demonstrate a crosstalk between microglia and retinal pericytes, evidencing a possible defensive role of microglia in the early phases of DR. ..
  16. Finlay D, Howes A, Vuori K. Caspase-8 as a potential mediator of pro-tumorigenic signals. Cell Cycle. 2009;8:3441-2 pubmed
  17. Qattan M, Bakker E, Rajendran R, Chen D, Saha V, Liu J, et al. Differential regulation of cell death pathways by the microenvironment correlates with chemoresistance and survival in leukaemia. PLoS ONE. 2017;12:e0178606 pubmed publisher
    ..Our data suggest that there is a correlation between microenvironment-induced ALL proliferation and altered response to chemotherapy. ..
  18. Belgiovine C, Bello E, Liguori M, Craparotta I, Mannarino L, Paracchini L, et al. Lurbinectedin reduces tumour-associated macrophages and the inflammatory tumour microenvironment in preclinical models. Br J Cancer. 2017;117:628-638 pubmed publisher
    ..These peculiar effects, combined with its intrinsic activity against cancer cells, make lurbinectedin a compound of particular interest in oncology. ..
  19. Peter M. Programmed cell death: Apoptosis meets necrosis. Nature. 2011;471:310-2 pubmed publisher
  20. Liu P, Hu Y, Kang B, Tseng Y, Wu P, Liang C, et al. Expression levels of cleaved caspase-3 and caspase-3 in tumorigenesis and prognosis of oral tongue squamous cell carcinoma. PLoS ONE. 2017;12:e0180620 pubmed publisher
    ..The co-expression level of cleaved caspase-3 and caspase-3 might be a prognostic biomarker for OTSCC patients, particular in those patients with certain tumor stages and cell differentiation status. ..
  21. Erdman V, Nasibullin T, Tuktarova I, Mustafina O. [Association of polymorphic markers of CASP8, BCL2 and BAX genes with aging and longevity]. Adv Gerontol. 2012;25:398-404 pubmed
    ..In female of longevity age, the number of CASP8*I/*D, BCL2*T/*T and BAX*A/*A genotype carriers was higher and number of CASP8*DI/*D, BCL2*C/*C, BAX*A/*G and BAX *G/*G genotype carriers was reduced. ..
  22. Kinkead L, Fayram D, Allen L. Francisella novicida inhibits spontaneous apoptosis and extends human neutrophil lifespan. J Leukoc Biol. 2017;102:815-828 pubmed publisher
  23. Schoenhacker Alte B, Mohr T, Pirker C, Kryeziu K, Kuhn P, Buck A, et al. Sensitivity towards the GRP78 inhibitor KP1339/IT-139 is characterized by apoptosis induction via caspase 8 upon disruption of ER homeostasis. Cancer Lett. 2017;404:79-88 pubmed publisher
    ..low-responsive cells executed cell cycle arrest in G2 phase, pronounced apoptosis induction via activation of caspase 8 was found in sensitive cells...
  24. Kroemer G. Regulated necrosis. Semin Cell Dev Biol. 2014;35:1 pubmed publisher
  25. Mascarenhas D, Cerqueira D, Pereira M, Castanheira F, Fernandes T, Manin G, et al. Inhibition of caspase-1 or gasdermin-D enable caspase-8 activation in the Naip5/NLRC4/ASC inflammasome. PLoS Pathog. 2017;13:e1006502 pubmed publisher
    ..Our data suggest that caspase-8 activation in the Naip5/NLRC4/ASC inflammasome enable induction of cell death when caspase-1 or gasdermin-D is suppressed. ..
  26. Zhang Z, Li H, Chen S, Li Y, Cui Z, Ma J. MicroRNA-122 regulates caspase-8 and promotes the apoptosis of mouse cardiomyocytes. Braz J Med Biol Res. 2017;50:e5760 pubmed publisher
    ..01) and reduced by miR-122 knockdown (P<0.001). These results suggest an inductive role of miR-122 in cardiomyocyte apoptosis, which may be related to its regulation on caspase-8. ..
  27. Lin B, Zhu M, Wang W, Li W, Dong X, Chen Y, et al. Structural basis for alpha fetoprotein-mediated inhibition of caspase-3 activity in hepatocellular carcinoma cells. Int J Cancer. 2017;141:1413-1421 pubmed publisher
    ..The results further demonstrated that AFP plays a critical role in the inhibition of the apoptotic signal transduction that mediated by caspase-3. Thus, AFP might represent a novel biotarget for the therapy of HCC patients. ..
  28. Boege Y, Malehmir M, Healy M, Bettermann K, Lorentzen A, Vucur M, et al. A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development. Cancer Cell. 2017;32:342-359.e10 pubmed publisher
    ..It may represent a DNA damage-sensing mechanism in hepatocytes that can act via JNK and subsequent phosphorylation of the histone variant H2AX. ..
  29. Jakovljević K, Matić I, Stanojkovic T, Krivokuca A, Marković V, Joksović M, et al. Synthesis, antioxidant and antiproliferative activities of 1,3,4-thiadiazoles derived from phenolic acids. Bioorg Med Chem Lett. 2017;27:3709-3715 pubmed publisher
    ..Furthermore, compounds 3c, 3'c, 3'g and 3'h showed the ability to down-regulate the MMP2 and VEGFA expression levels in the treated HL-60 cells when compared with the control cell samples. ..
  30. Farr J, Xu M, Weivoda M, Monroe D, Fraser D, Onken J, et al. Targeting cellular senescence prevents age-related bone loss in mice. Nat Med. 2017;23:1072-1079 pubmed publisher
    ..In particular, we used either genetic (i.e., the INK-ATTAC 'suicide' transgene encoding an inducible caspase 8 expressed specifically in senescent cells) or pharmacological (i.e...
  31. Dupaul Chicoine J, Saleh M. A new path to IL-1? production controlled by caspase-8. Nat Immunol. 2012;13:211-2 pubmed publisher
  32. Rabouille C. KRS: A cut away from release in exosomes. J Cell Biol. 2017;216:1891-1893 pubmed publisher
    ..Kim et al. (2017. J. Cell Biol. now demonstrate that cleavage of the KRS by caspase-8 inside cells triggers its interaction with syntenin and its release in inflammatory exosomes. ..
  33. Shashni B, Sharma K, Singh R, Sakharkar K, Dhillon S, Nagasaki Y, et al. Coffee component hydroxyl hydroquinone (HHQ) as a putative ligand for PPAR gamma and implications in breast cancer. BMC Genomics. 2013;14 Suppl 5:S6 pubmed publisher
    ..HHQ was also validated as a ligand for PPAR? by docking procedure. This is the first report on the anti-breast cancer (in vitro) activity of HHQ. ..
  34. Lenzi M, Malaguti M, Cocchi V, Hrelia S, Hrelia P. Castanea sativa Mill. bark extract exhibits chemopreventive properties triggering extrinsic apoptotic pathway in Jurkat cells. BMC Complement Altern Med. 2017;17:251 pubmed publisher
    ..Our data suggest that CSM bark extract might be considered an interesting potential anti-cancer agent, since it induces apoptosis in cancer cells without appreciable cytotoxic effects on non-transformed cells. ..
  35. Rauch I, Deets K, Ji D, von Moltke J, Tenthorey J, Lee A, et al. NAIP-NLRC4 Inflammasomes Coordinate Intestinal Epithelial Cell Expulsion with Eicosanoid and IL-18 Release via Activation of Caspase-1 and -8. Immunity. 2017;46:649-659 pubmed publisher
    ..Thus, a coordinated IEC-intrinsic, Caspase-1 and -8 inflammasome response plays a key role in intestinal immune defense and pathology. ..
  36. Dong K, Han L, Liu J, Wang F, Sun X. RNA Interference Reveals the Coregulatory Effects of Cylindromatosis on Apoptosis and Necroptosis of Photoreceptor Cells in Experimental Retinal Detachment. Am J Pathol. 2017;187:1763-1771 pubmed publisher
    ..Knockdown of cylindromatosis expression led to inhibition of caspase 8 activity, a decrease in the number of apoptotic photoreceptor cells, and an increase in the ubiquitination level ..
  37. Vince J, Tschopp J. IRF-3 partners Bax in a viral-induced dance macabre. EMBO J. 2010;29:1627-8 pubmed publisher
  38. Kim S, Kim H, Park M, Cho S, Goughnour P, Han D, et al. Caspase-8 controls the secretion of inflammatory lysyl-tRNA synthetase in exosomes from cancer cells. J Cell Biol. 2017;216:2201-2216 pubmed publisher
  39. Panayotova Dimitrova D, Feoktistova M, Ploesser M, Kellert B, Hupe M, Horn S, et al. cFLIP regulates skin homeostasis and protects against TNF-induced keratinocyte apoptosis. Cell Rep. 2013;5:397-408 pubmed publisher
    ..Our data demonstrate the importance of cFLIP for the integrity of the epidermis and for silencing of spontaneous skin inflammation. ..
  40. Fatehchand K, Santhanam R, Shen B, Erickson E, Gautam S, Elavazhagan S, et al. Active hexose-correlated compound enhances extrinsic-pathway-mediated apoptosis of Acute Myeloid Leukemic cells. PLoS ONE. 2017;12:e0181729 pubmed publisher
    ..These results uncover a mechanism by which AHCC leads to AML-cell specific death, and also lend support for the further investigation of AHCC as a potential adjuvant for the treatment of AML. ..
  41. Ofengeim D, Ito Y, Najafov A, Zhang Y, Shan B, Dewitt J, et al. Activation of necroptosis in multiple sclerosis. Cell Rep. 2015;10:1836-49 pubmed
    ..Our findings demonstrate that necroptosis is involved in MS and suggest that targeting RIPK1 may represent a therapeutic strategy for MS. ..
  42. Horn S, Hughes M, Schilling R, Sticht C, Tenev T, Ploesser M, et al. Caspase-10 Negatively Regulates Caspase-8-Mediated Cell Death, Switching the Response to CD95L in Favor of NF-κB Activation and Cell Survival. Cell Rep. 2017;19:785-797 pubmed publisher
    ..Thus, our data are consistent with a model in which both caspase-10 and cFLIP coordinately regulate CD95L-mediated signaling for death or survival. ..
  43. Sarkar M, Ghosh S, Bhuniya A, Ghosh T, Guha I, Barik S, et al. Neem leaf glycoprotein prevents post-surgical sarcoma recurrence in Swiss mice by differentially regulating cytotoxic T and myeloid-derived suppressor cells. PLoS ONE. 2017;12:e0175540 pubmed publisher
    ..These mice also exhibited increased MDSCs along with decreased levels of Caspase 3, Caspase 8 and increased cFLIP expression...
  44. Vandenabeele P, Melino G. The flick of a switch: which death program to choose?. Cell Death Differ. 2012;19:1093-5 pubmed publisher
  45. Reynaud K, Driancourt M. Oocyte attrition. Mol Cell Endocrinol. 2000;163:101-8 pubmed
    ..Fas ligand binding on oocytic fas may result in caspase 8 activation. Two pathways inducing oocyte apoptosis may then be operating...
  46. Bailey L, Alahari S, Tagliaferro A, Post M, Caniggia I. Augmented trophoblast cell death in preeclampsia can proceed via ceramide-mediated necroptosis. Cell Death Dis. 2017;8:e2590 pubmed publisher
    ..This study is the first to report that trophoblast cells undergo CER-induced necroptotic cell death, thereby contributing to the increased placental dysfunction and cell death found in preeclampsia. ..