Gene Symbol: caspase-8
Description: caspase 8
Alias: ALPS2B, CAP4, Casp-8, FLICE, MACH, MCH5, caspase-8, FADD-homologous ICE/CED-3-like protease, FADD-like ICE, ICE-like apoptotic protease 5, MACH-alpha-1/2/3 protein, MACH-beta-1/2/3/4 protein, MORT1-associated ced-3 homolog, apoptotic cysteine protease, apoptotic protease Mch-5, caspase 8, apoptosis-related cysteine peptidase, caspase 8, apoptosis-related cysteine protease
Species: human
Products:     caspase-8

Top Publications

  1. Carrington P, Sandu C, Wei Y, Hill J, Morisawa G, Huang T, et al. The structure of FADD and its mode of interaction with procaspase-8. Mol Cell. 2006;22:599-610 pubmed
    ..The structure of FADD and its functional characterization, therefore, illustrate the architecture of key components in the death-inducing signaling complex. ..
  2. Xiao M, Chang L, Li W, Du Y, Pan Y, Zhang D, et al. Genetic polymorphisms of the CASP8 gene promoter may not be associated with colorectal cancer in Han Chinese from southwest China. PLoS ONE. 2013;8:e67577 pubmed publisher
    b>Caspase 8 (CASP8) plays a critical role in the apoptotic pathway and aberrant regulation of this pathway causes many diseases including cancers...
  3. Heijink D, Kleibeuker J, Jalving M, Boersma van Ek W, Koornstra J, Wesseling J, et al. Independent induction of caspase-8 and cFLIP expression during colorectal carcinogenesis in sporadic and HNPCC adenomas and carcinomas. Cell Oncol. 2007;29:409-19 pubmed
    ..Important determinants of TRAIL sensitivity are two intracellular proteins of the TRAIL pathway, caspase-8 and its anti-apoptotic competitor cellular Flice-Like Inhibitory Protein (cFLIP).
  4. Beaudouin J, Liesche C, Aschenbrenner S, Horner M, Eils R. Caspase-8 cleaves its substrates from the plasma membrane upon CD95-induced apoptosis. Cell Death Differ. 2013;20:599-610 pubmed publisher
    ..Subcellular compartmentalization of caspase-8 activity may serve to restrict enzymatic activity before mitochondrial pathway activation and offers new possibilities to interfere with apoptotic sensitivity of the cells. ..
  5. Lázcoz P, MUNOZ J, Nistal M, Pestaña A, Encio I, Castresana J. Frequent promoter hypermethylation of RASSF1A and CASP8 in neuroblastoma. BMC Cancer. 2006;6:254 pubmed
    ..2) Promoter hypermethylation of RASSF1A and CASP8 occurs at a high frequency in neuroblastomas. ..
  6. Tenev T, Bianchi K, Darding M, Broemer M, Langlais C, Wallberg F, et al. The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs. Mol Cell. 2011;43:432-48 pubmed publisher
    ..Together, our observations shed new light on fundamental mechanisms by which chemotherapeutics may kill cancer cells. ..
  7. Lan Q, Morton L, Armstrong B, Hartge P, Menashe I, Zheng T, et al. Genetic variation in caspase genes and risk of non-Hodgkin lymphoma: a pooled analysis of 3 population-based case-control studies. Blood. 2009;114:264-7 pubmed publisher
    ..It is noteworthy that genetic variants in CASP8 were associated with risk of all major NHL subtypes. Our findings suggest that genetic variation in caspases may play an important role in lymphomagenesis. ..
  8. Gonzalvez F, Schug Z, Houtkooper R, MacKenzie E, Brooks D, Wanders R, et al. Cardiolipin provides an essential activating platform for caspase-8 on mitochondria. J Cell Biol. 2008;183:681-96 pubmed publisher
  9. Feoktistova M, Geserick P, Kellert B, Dimitrova D, Langlais C, Hupe M, et al. cIAPs block Ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms. Mol Cell. 2011;43:449-63 pubmed publisher
    ..The differential quality of cell death mediated by the Ripoptosome may cause important pathophysiological consequences during inflammatory responses. ..

More Information


  1. Schug Z, Gonzalvez F, Houtkooper R, Vaz F, Gottlieb E. BID is cleaved by caspase-8 within a native complex on the mitochondrial membrane. Cell Death Differ. 2011;18:538-48 pubmed publisher
    ..Our findings indicate that during extrinsic apoptosis, caspase-8 can specifically target BID where it is mostly needed, on the surface of mitochondria. ..
  2. Liu B, Zhang Y, Jin M, Ni Q, Liang X, Ma X, et al. Association of selected polymorphisms of CCND1, p21, and caspase8 with colorectal cancer risk. Mol Carcinog. 2010;49:75-84 pubmed publisher
    ..25). Our findings suggest that the selected polymorphisms of p21, CCND1, and caspase8 may not contribute to the risk of colorectal cancer. ..
  3. Haiman C, Garcia R, Kolonel L, Henderson B, Wu A, Le Marchand L. A promoter polymorphism in the CASP8 gene is not associated with cancer risk. Nat Genet. 2008;40:259-60; author reply 260-1 pubmed publisher
  4. Stupack D. Caspase-8 as a therapeutic target in cancer. Cancer Lett. 2013;332:133-40 pubmed publisher
    ..Care is warranted, and the role of caspase-8 should be addressed on a case by case basis. ..
  5. Barrett J, Iles M, Harland M, Taylor J, Aitken J, Andresen P, et al. Genome-wide association study identifies three new melanoma susceptibility loci. Nat Genet. 2011;43:1108-13 pubmed publisher
    ..6 × 10(-7) under a fixed-effects model and P = 1.2 × 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series. ..
  6. Gangwar R, Mandhani A, Mittal R. Caspase 9 and caspase 8 gene polymorphisms and susceptibility to bladder cancer in north Indian population. Ann Surg Oncol. 2009;16:2028-34 pubmed publisher
    ..Our aim was to investigate the association of Caspase 9 and Caspase 8 gene polymorphism with bladder cancer (BC) susceptibility...
  7. Torres V, Mielgo A, Barbero S, Hsiao R, Wilkins J, Stupack D. Rab5 mediates caspase-8-promoted cell motility and metastasis. Mol Biol Cell. 2010;21:369-76 pubmed publisher
    ..These studies identify Rab5 as a key integrator of caspase-8-mediated signal transduction downstream of integrins, regulating cell survival and migration in vivo and in vitro. ..
  8. Estornes Y, Toscano F, Virard F, Jacquemin G, Pierrot A, Vanbervliet B, et al. dsRNA induces apoptosis through an atypical death complex associating TLR3 to caspase-8. Cell Death Differ. 2012;19:1482-94 pubmed publisher
    ..Our findings uncover a novel aspect of the molecular mechanisms involved during apoptosis induced by the innate immune receptor TLR3 in cancer cells. ..
  9. Gonzalvez F, Lawrence D, Yang B, Yee S, Pitti R, Marsters S, et al. TRAF2 Sets a threshold for extrinsic apoptosis by tagging caspase-8 with a ubiquitin shutoff timer. Mol Cell. 2012;48:888-99 pubmed publisher
    ..Thus, TRAF2 sets a critical barrier for cell-extrinsic apoptosis commitment by tagging activated caspase-8 with a K48-ubiquitin shutoff timer. These results may have important implications for caspase regulation mechanisms. ..
  10. Torres V, Mielgo A, Barilà D, Anderson D, Stupack D. Caspase 8 promotes peripheral localization and activation of Rab5. J Biol Chem. 2008;283:36280-9 pubmed publisher
    b>Caspase 8 is a cysteine protease that initiates apoptotic signaling via the extrinsic pathway in a manner dependent upon association with early endosomes...
  11. Finlay D, Howes A, Vuori K. Critical role for caspase-8 in epidermal growth factor signaling. Cancer Res. 2009;69:5023-9 pubmed publisher
    ..As the EGF/Src pathway activity has been shown to promote oncogenic events, our findings that caspase-8 is necessary for these activities may help explain why it is rarely deleted or silenced in tumors. ..
  12. Camp N, Parry M, Knight S, Abo R, Elliott G, Rigas S, et al. Fine-mapping CASP8 risk variants in breast cancer. Cancer Epidemiol Biomarkers Prev. 2012;21:176-81 pubmed publisher
  13. Legarda Addison D, Hase H, O Donnell M, Ting A. NEMO/IKKgamma regulates an early NF-kappaB-independent cell-death checkpoint during TNF signaling. Cell Death Differ. 2009;16:1279-88 pubmed publisher
  14. Nie Z, Bren G, Vlahakis S, Schimnich A, Brenchley J, Trushin S, et al. Human immunodeficiency virus type 1 protease cleaves procaspase 8 in vivo. J Virol. 2007;81:6947-56 pubmed
    ..casp8p41 is specific to HIV-1 protease-induced death but not other caspase 8-dependent death stimuli...
  15. Jin Z, Li Y, Pitti R, Lawrence D, Pham V, Lill J, et al. Cullin3-based polyubiquitination and p62-dependent aggregation of caspase-8 mediate extrinsic apoptosis signaling. Cell. 2009;137:721-35 pubmed publisher
    ..These results identify a mechanism that positively controls apoptosis signaling by polyubiquitination and aggregation of a key initiator caspase. ..
  16. van Raam B, Salvesen G. Proliferative versus apoptotic functions of caspase-8 Hetero or homo: the caspase-8 dimer controls cell fate. Biochim Biophys Acta. 2012;1824:113-22 pubmed publisher
    ..This article is part of a Special Issue entitled: Proteolysis 50 years after the discovery of lysosome. ..
  17. Biton S, Ashkenazi A. NEMO and RIP1 control cell fate in response to extensive DNA damage via TNF-? feedforward signaling. Cell. 2011;145:92-103 pubmed publisher
    ..Thus, in the context of excessive DNA damage, ATM employs NEMO and RIP1 kinase through autocrine TNF-? signaling to switch on cytokine production and caspase activation. These results shed light on cell-fate regulation by ATM. ..
  18. Feig C, Tchikov V, Schütze S, Peter M. Palmitoylation of CD95 facilitates formation of SDS-stable receptor aggregates that initiate apoptosis signaling. EMBO J. 2007;26:221-31 pubmed
    ..Our data demonstrate that SDS-stable forms of CD95 are the sites of apoptosis initiation and represent an important early step in apoptosis signaling through CD95 before activation of caspases. ..
  19. Reinehr R, Sommerfeld A, Keitel V, Grether Beck S, Haussinger D. Amplification of CD95 activation by caspase 8-induced endosomal acidification in rat hepatocytes. J Biol Chem. 2008;283:2211-22 pubmed
    ..Interestingly, caspase 8 inhibitors abolished these CD95L-induced signaling events, including the increase in cytosolic [Cl(-)], ..
  20. Frank B, Rigas S, Bermejo J, Wiestler M, Wagner K, Hemminki K, et al. The CASP8 -652 6N del promoter polymorphism and breast cancer risk: a multicenter study. Breast Cancer Res Treat. 2008;111:139-44 pubmed
    ..The combined per allele odds ratio (OR) was 0.97 (95% confidence interval (CI), 95% CI = 0.93-1.02). The present result indicates that the CASP8 -652 6N del variant has no significant effect on BC risk in Europeans. ..
  21. Theodoropoulos G, Gazouli M, Vaiopoulou A, Leandrou M, Nikouli S, Vassou E, et al. Polymorphisms of caspase 8 and caspase 9 gene and colorectal cancer susceptibility and prognosis. Int J Colorectal Dis. 2011;26:1113-8 pubmed publisher
    ..The CASP9 -1263 A>G polymorphism was observed to play a protective role in CRC predisposition, while the CASP9 -1263 GG genotype may confer a better prognosis at CRC patients. ..
  22. Yin M, Yan J, Wei S, Wei Q. CASP8 polymorphisms contribute to cancer susceptibility: evidence from a meta-analysis of 23 publications with 55 individual studies. Carcinogenesis. 2010;31:850-7 pubmed publisher
    Several potentially functional polymorphisms of CASP8 encoding an apoptotic enzyme, caspase 8, have been implicated in cancer risk, but individually published studies showed inconclusive results...
  23. Ma X, Zhang J, Liu S, Huang Y, Chen B, Wang D. Polymorphisms in the CASP8 gene and the risk of epithelial ovarian cancer. Gynecol Oncol. 2011;122:554-9 pubmed publisher
    ..Furthermore, these protective effects may be due to the dysfunctional expression of caspase-8 caused by the -652 6N del variant in the promoter. ..
  24. Kamimatsuse A, Matsuura K, Moriya S, Fukuba I, Yamaoka H, Fukuda E, et al. Detection of CpG island hypermethylation of caspase-8 in neuroblastoma using an oligonucleotide array. Pediatr Blood Cancer. 2009;52:777-83 pubmed publisher utilized oligoarrays to evaluate the methylation status of a CpG island located between exons 2 and 3 of caspase 8 in neuroblastomas...
  25. Dickens L, Boyd R, Jukes Jones R, Hughes M, Robinson G, Fairall L, et al. A death effector domain chain DISC model reveals a crucial role for caspase-8 chain assembly in mediating apoptotic cell death. Mol Cell. 2012;47:291-305 pubmed publisher
    ..This provides direct experimental evidence for a DISC model in which DED chain assembly drives caspase-8 dimerization/activation, thereby triggering cell death. ..
  26. Xu B, Zhou Z, Li Y, Wang L, Yang L, Zhou B, et al. Clinicopathological significance of caspase-8 and caspase-10 expression in rectal cancer. Oncology. 2008;74:229-36 pubmed publisher
    ..Caspase-10 expression was down-regulated in both rectal adenomas and cancers, and was further related to differentiation. Caspase-8 and -10 may be involved in the pathogenesis of rectal cancer. ..
  27. Bertrand M, Milutinovic S, Dickson K, Ho W, Boudreault A, Durkin J, et al. cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Mol Cell. 2008;30:689-700 pubmed publisher
    ..When deubiquitinated by AEG40730 treatment, RIP1 binds caspase-8 and induces apoptosis. These findings provide insights into the function of the IAPs and provide new therapeutic opportunities in the treatment of cancer. ..
  28. Wang L, Du F, Wang X. TNF-alpha induces two distinct caspase-8 activation pathways. Cell. 2008;133:693-703 pubmed publisher
    ..These findings revealed that TNF-alpha is able to induce apoptosis via two distinct caspase-8 activation pathways that are differentially regulated by cIAP1/2 and c-FLIP. ..
  29. Kominami K, Nakabayashi J, Nagai T, Tsujimura Y, Chiba K, Kimura H, et al. The molecular mechanism of apoptosis upon caspase-8 activation: quantitative experimental validation of a mathematical model. Biochim Biophys Acta. 2012;1823:1825-40 pubmed publisher
    ..Taken together, our findings demonstrate the precise cascade of CASP8-mediated apoptotic signals through the extrinsic pathway. ..
  30. Schleich K, Warnken U, Fricker N, Oztürk S, Richter P, Kammerer K, et al. Stoichiometry of the CD95 death-inducing signaling complex: experimental and modeling evidence for a death effector domain chain model. Mol Cell. 2012;47:306-19 pubmed publisher
    ..Taken together, our findings provide an enhanced understanding of caspase-8 activation and initiation of apoptosis at the DISC. ..
  31. Yang Q, Kiernan C, Tian Y, Salwen H, Chlenski A, Brumback B, et al. Methylation of CASP8, DCR2, and HIN-1 in neuroblastoma is associated with poor outcome. Clin Cancer Res. 2007;13:3191-7 pubmed
    ..055). Our study indicates that clinically aggressive neuroblastoma tumors have aberrant methylation of multiple genes and provides a rationale for exploring treatment strategies that include demethylating agents. ..
  32. Thorpe J, Christian P, Schwarze S. Proteasome inhibition blocks caspase-8 degradation and sensitizes prostate cancer cells to death receptor-mediated apoptosis. Prostate. 2008;68:200-9 pubmed
    ..This study suggests that the clinical efficacy of Velcade may result, at least in part, from the activity of death ligands. ..
  33. Jia S, Parodo J, Kapus A, Rotstein O, Marshall J. Dynamic regulation of neutrophil survival through tyrosine phosphorylation or dephosphorylation of caspase-8. J Biol Chem. 2008;283:5402-13 pubmed
  34. Tomar D, Prajapati P, Sripada L, Singh K, Singh R, Singh A, et al. TRIM13 regulates caspase-8 ubiquitination, translocation to autophagosomes and activation during ER stress induced cell death. Biochim Biophys Acta. 2013;1833:3134-3144 pubmed publisher
    ..This study first time demonstrated the role of TRIM13 as novel regulator of caspase-8 activation and cell death during ER stress. ..
  35. Peng C, Cho Y, Zhu F, Zhang J, Wen W, Xu Y, et al. Phosphorylation of caspase-8 (Thr-263) by ribosomal S6 kinase 2 (RSK2) mediates caspase-8 ubiquitination and stability. J Biol Chem. 2011;286:6946-54 pubmed publisher
    ..Finally, RSK2 blocks Fas-induced apoptosis through its phosphorylation of caspase-8. These data provide a direct link between RSK2 and caspase-8 and identify a novel molecular mechanism for caspase-8 modulation by RSK2. ..
  36. Rajput A, Kovalenko A, Bogdanov K, Yang S, Kang T, Kim J, et al. RIG-I RNA helicase activation of IRF3 transcription factor is negatively regulated by caspase-8-mediated cleavage of the RIP1 protein. Immunity. 2011;34:340-51 pubmed publisher
    ..The dependence of RIP1 cleavage on the same molecular change as that facilitating RIG-I signaling allows for RIG-I signaling to be restricted in its duration without compromising its initial activation. ..
  37. Conus S, Pop C, Snipas S, Salvesen G, Simon H. Cathepsin D primes caspase-8 activation by multiple intra-chain proteolysis. J Biol Chem. 2012;287:21142-51 pubmed publisher
    ..As cathepsin D is ubiquitously expressed, this may represent a general mechanism to induce apoptosis in a variety of immune and nonimmune cells. ..
  38. Zhang F, Yang Y, Guo C, Wang Y. CASP8 -652 6N del polymorphism and cancer risk: a meta-analysis of 30 case-control studies in 50,112 subjects. Mutagenesis. 2012;27:559-66 pubmed publisher
    ..However, further research, such as studies focusing on additional ethnic groups and cancer types, is needed to provide a more exact and comprehensive synthesis conclusion. ..
  39. Liamarkopoulos E, Gazouli M, Aravantinos G, Tzanakis N, Theodoropoulos G, Rizos S, et al. Caspase 8 and caspase 9 gene polymorphisms and susceptibility to gastric cancer. Gastric Cancer. 2011;14:317-21 pubmed publisher
    ..The CASP8 -652 6N ins/del and the CASP9 -1263 A>G polymorphisms were observed to play a protective role in GC predisposition. ..
  40. Löder S, Fakler M, Schoeneberger H, Cristofanon S, Leibacher J, Vanlangenakker N, et al. RIP1 is required for IAP inhibitor-mediated sensitization of childhood acute leukemia cells to chemotherapy-induced apoptosis. Leukemia. 2012;26:1020-9 pubmed publisher
    ..These data have important implications for developing apoptosis-targeted therapies in childhood leukemia. ..
  41. Kim S, Ohoka N, Okuhira K, Sai K, Nishimaki Mogami T, Naito M. Modulation of RIP1 ubiquitylation and distribution by MeBS to sensitize cancer cells to tumor necrosis factor ?-induced apoptosis. Cancer Sci. 2010;101:2425-9 pubmed publisher
    ..These results indicate an important role of RIP1 in apoptosis induced by combined treatment with TNF? and MeBS, suggesting that MeBS sensitizes cancer cells to apoptosis by modulating RIP1 ubiquitylation and distribution. ..
  42. Guicciardi M, Mott J, Bronk S, Kurita S, Fingas C, Gores G. Cellular inhibitor of apoptosis 1 (cIAP-1) degradation by caspase 8 during TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Exp Cell Res. 2011;317:107-16 pubmed publisher
    ..TRAIL-induced loss of cIAP-1 and XIAP requires caspase activity. In particular, caspase 8 knockdown stabilizes both cIAP-1 and XIAP, while caspase 9 knockdown prevents XIAP, but not cIAP-1 degradation...
  43. Sun T, Gao Y, Tan W, Ma S, Shi Y, Yao J, et al. A six-nucleotide insertion-deletion polymorphism in the CASP8 promoter is associated with susceptibility to multiple cancers. Nat Genet. 2007;39:605-13 pubmed
    ..These results support the hypothesis that genetic variants influencing immune status modify cancer susceptibility. ..
  44. Kleber S, Sancho Martinez I, Wiestler B, Beisel A, Gieffers C, Hill O, et al. Yes and PI3K bind CD95 to signal invasion of glioblastoma. Cancer Cell. 2008;13:235-48 pubmed publisher
    ..Our results uncover CD95 as an activator of PI3K and, most importantly, as a crucial trigger of basal invasion of glioblastoma in vivo. ..
  45. Shephard N, Abo R, Rigas S, Frank B, Lin W, Brock I, et al. A breast cancer risk haplotype in the caspase-8 gene. Cancer Res. 2009;69:2724-8 pubmed publisher
    ..An understanding of the mode of action of these alleles will aid risk assessment and may lead to the identification of novel treatment targets in breast cancer. ..
  46. Kang T, Oh G, Scandella E, Bolinger B, Ludewig B, Kovalenko A, et al. Mutation of a self-processing site in caspase-8 compromises its apoptotic but not its nonapoptotic functions in bacterial artificial chromosome-transgenic mice. J Immunol. 2008;181:2522-32 pubmed
  47. Lan Q, Zheng T, Chanock S, Zhang Y, Shen M, Wang S, et al. Genetic variants in caspase genes and susceptibility to non-Hodgkin lymphoma. Carcinogenesis. 2007;28:823-7 pubmed
    ..The striking protective associations observed for polymorphisms in all four genes for NHL and/or one or more subtypes suggest that genetic variation in CASP genes may play an important role in the etiology of NHL. ..
  48. Cox A, Dunning A, Garcia Closas M, Balasubramanian S, Reed M, Pooley K, et al. A common coding variant in CASP8 is associated with breast cancer risk. Nat Genet. 2007;39:352-8 pubmed
    ..13) and 1.16 (95% c.i.: 1.08-1.25), respectively; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies. ..
  49. Senft J, Helfer B, Frisch S. Caspase-8 interacts with the p85 subunit of phosphatidylinositol 3-kinase to regulate cell adhesion and motility. Cancer Res. 2007;67:11505-9 pubmed
    ..These results suggest that caspase-8 phosphorylation converts it from a proapoptotic factor to a cell motility factor that, through tyrosine-380, interacts with p85, an established cell migration component. ..
  50. Barbero S, Barilà D, Mielgo A, Stagni V, Clair K, Stupack D. Identification of a critical tyrosine residue in caspase 8 that promotes cell migration. J Biol Chem. 2008;283:13031-4 pubmed publisher
    b>Caspase 8 is a critical upstream initiator of programmed cell death but, paradoxically, has also been shown to promote cell migration...
  51. Pittman A, Broderick P, Sullivan K, Fielding S, Webb E, Penegar S, et al. CASP8 variants D302H and -652 6N ins/del do not influence the risk of colorectal cancer in the United Kingdom population. Br J Cancer. 2008;98:1434-6 pubmed publisher
    ..The implications of our findings both in terms of population-specific effects and publication bias are discussed. ..
  52. O Donnell M, Perez Jimenez E, Oberst A, Ng A, Massoumi R, Xavier R, et al. Caspase 8 inhibits programmed necrosis by processing CYLD. Nat Cell Biol. 2011;13:1437-42 pubmed publisher
    b>Caspase 8 initiates apoptosis downstream of TNF death receptors by undergoing autocleavage and processing the executioner caspase 3 (ref. 1)...
  53. Oberst A, Pop C, Tremblay A, Blais V, Denault J, Salvesen G, et al. Inducible dimerization and inducible cleavage reveal a requirement for both processes in caspase-8 activation. J Biol Chem. 2010;285:16632-42 pubmed publisher
  54. Ni C, Ye Y, Wang M, Qian H, Song Z, Jia X, et al. A six-nucleotide insertion-deletion polymorphism in the CASP8 promoter is associated with risk of coal workers' pneumoconiosis. J Toxicol Environ Health A. 2009;72:712-6 pubmed publisher
    ..These findings suggested that CASP8-652 6N ins/del polymorphism may contribute to the genetic susceptibility for CWP development. ..
  55. Xiao M, Zhang D, Zeng Y, Cheng Y, Yao Y. Polymorphisms in the promoter region of the CASP8 gene are not associated with non-Hodgkin's lymphoma in Chinese patients. Ann Hematol. 2011;90:1137-44 pubmed publisher
    ..Our negative results gave no support for an active role for these genetic variants in conferring NHL in Chinese patients. ..
  56. Iwasawa R, Mahul Mellier A, Datler C, Pazarentzos E, Grimm S. Fis1 and Bap31 bridge the mitochondria-ER interface to establish a platform for apoptosis induction. EMBO J. 2011;30:556-68 pubmed publisher
    ..Hence, the Fis1-Bap31 complex (ARCosome) that spans the mitochondria-ER interface serves as a platform to activate the initiator procaspase-8, and thereby bridges two critical organelles for apoptosis signalling. ..
  57. Kavuri S, Geserick P, Berg D, Dimitrova D, Feoktistova M, Siegmund D, et al. Cellular FLICE-inhibitory protein (cFLIP) isoforms block CD95- and TRAIL death receptor-induced gene induction irrespective of processing of caspase-8 or cFLIP in the death-inducing signaling complex. J Biol Chem. 2011;286:16631-46 pubmed publisher
    ..cFLIP-mediated inhibition of CD95 and TRAIL DR could be of crucial importance during keratinocyte skin carcinogenesis and for the activation of innate and/or adaptive immune responses triggered by DR activation in the skin. ..
  58. Wang M, Zhang Z, Tian Y, Shao J, Zhang Z. A six-nucleotide insertion-deletion polymorphism in the CASP8 promoter associated with risk and progression of bladder cancer. Clin Cancer Res. 2009;15:2567-72 pubmed publisher
    ..Larger studies are warranted to validate our findings. ..
  59. Milovic Holm K, Krieghoff E, Jensen K, Will H, Hofmann T. FLASH links the CD95 signaling pathway to the cell nucleus and nuclear bodies. EMBO J. 2007;26:391-401 pubmed
    Caspase-8-binding protein FLICE-associated huge protein (FLASH) has been proposed to regulate death receptor CD95-induced apoptosis through facilitating caspase-8 activation at the death-inducing signaling complex...
  60. Yao Z, Duan S, Hou D, Heese K, Wu M. Death effector domain DEDa, a self-cleaved product of caspase-8/Mch5, translocates to the nucleus by binding to ERK1/2 and upregulates procaspase-8 expression via a p53-dependent mechanism. EMBO J. 2007;26:1068-80 pubmed
    ..Here, we demonstrate that the prodomain of the caspase-8/Mch5 can be further cleaved between two tandemly repeated DEDs (DEDa-DEDb) at the amino-acid residue Asp129 by caspase-8 ..
  61. Liu J, Uematsu H, Tsuchida N, Ikeda M. Association of caspase-8 mutation with chemoresistance to cisplatin in HOC313 head and neck squamous cell carcinoma cells. Biochem Biophys Res Commun. 2009;390:989-94 pubmed publisher
    ..These results indicate that the loss of caspase-8 plays an important role in acquisition of chemoresistance to cisplatin in HOC313 cells. ..
  62. Sergentanis T, Economopoulos K. Association of two CASP8 polymorphisms with breast cancer risk: a meta-analysis. Breast Cancer Res Treat. 2010;120:229-34 pubmed publisher
    ..Further studies are needed to gain the optimal power on -652 6N del, especially in Chinese subjects, as well as to gain insight into D302H in Chinese populations. ..
  63. Cho Y, Challa S, Moquin D, Genga R, Ray T, Guildford M, et al. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell. 2009;137:1112-23 pubmed publisher
    ..Our findings suggest that RIP3 controls programmed necrosis by initiating the pronecrotic kinase cascade, and that this is necessary for the inflammatory response against virus infections. ..
  64. He S, Wang L, Miao L, Wang T, Du F, Zhao L, et al. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell. 2009;137:1100-11 pubmed publisher
    ..These data indicate RIP3 as the determinant for cellular necrosis in response to TNF-alpha family of death-inducing cytokines. ..
  65. Kawadler H, Gantz M, Riley J, Yang X. The paracaspase MALT1 controls caspase-8 activation during lymphocyte proliferation. Mol Cell. 2008;31:415-21 pubmed publisher
    ..Our results reveal a mechanism that utilizes a protease potentially deadly to the cell for proliferative signaling and demonstrate a functional connection between the caspase and paracaspase families to enable nonapoptotic processes. ..
  66. Hashemi M, Eskandari Nasab E, Fazaeli A, Rezaei H, Mashhadi M, Arbabi F, et al. Bi-directional PCR allele-specific amplification (bi-PASA) for detection of caspase-8 -652 6N ins/del promoter polymorphism (rs3834129) in breast cancer. Gene. 2012;505:176-9 pubmed publisher
    ..Further studies in other populations with larger samples are needed to confirm these findings. ..
  67. Finlay D, Vuori K. Novel noncatalytic role for caspase-8 in promoting SRC-mediated adhesion and Erk signaling in neuroblastoma cells. Cancer Res. 2007;67:11704-11 pubmed
    ..This protein complex association of caspase-8 and Src, and concomitant downstream signaling events, may help reconcile why a potential tumor suppressor such as caspase-8 is rarely absent in cancers. ..
  68. Martinez R, Setien F, Voelter C, Casado S, Quesada M, Schackert G, et al. CpG island promoter hypermethylation of the pro-apoptotic gene caspase-8 is a common hallmark of relapsed glioblastoma multiforme. Carcinogenesis. 2007;28:1264-8 pubmed
    ..These remarkable findings may foster the development of therapeutic approaches using DNA demethylating drugs and activators of the extrinsic apoptotic pathway to improve the dismal prognosis of GBM. ..
  69. Mahul Mellier A, Pazarentzos E, Datler C, Iwasawa R, Abuali G, Lin B, et al. De-ubiquitinating protease USP2a targets RIP1 and TRAF2 to mediate cell death by TNF. Cell Death Differ. 2012;19:891-9 pubmed publisher
    ..Consequently, downregulation of USP2a promotes NF-?B activation and protects cells against TNF-induced cell death. ..
  70. de Martino M, Haitel A, Schatzl G, Klingler H, Klatte T. The CASP8 -652 6N insertion/deletion promoter polymorphism is associated with renal cell carcinoma risk and metastasis. J Urol. 2013;190:717-22 pubmed publisher
    ..The del/del genotype of the CASP8 -652 6N ins/del promoter polymorphism decreases the overall risk of renal cell carcinoma. It may be associated with a decreased risk of metastasis. Larger studies are warranted to validate our findings. ..