Gene Symbol: Cflar
Description: CASP8 and FADD-like apoptosis regulator
Alias: 2310024N18Rik, A430105C05Rik, CLARP, Cash, Casper, FLAME, FLAME-1, Flip, Gm9845, I-FLICE, MRIT, c-Flip, CASP8 and FADD-like apoptosis regulator, FADD-like antiapoptotic molecule 1, MACH-related inducer of toxicity, caspase homolog, caspase-eight-related protein, caspase-like apoptosis regulatory protein, cellular FLICE-like inhibitory protein, inhibitor of FLICE, usurpin
Species: mouse
Products:     Cflar

Top Publications

  1. Bergman M, Cilio C, Penha Gonçalves C, Lamhamedi Cherradi S, Lofgren A, Colucci F, et al. CTLA-4-/- mice display T cell-apoptosis resistance resembling that ascribed to autoimmune-prone non-obese diabetic (NOD) mice. J Autoimmun. 2001;16:105-13 pubmed
    ..This reinforces the notion that CTLA-4 contributes to the pathogenesis of autoimmune diabetes. ..
  2. Moubarak R, Sole C, Pascual M, Gutierrez H, Llovera M, Perez Garcia M, et al. The death receptor antagonist FLIP-L interacts with Trk and is necessary for neurite outgrowth induced by neurotrophins. J Neurosci. 2010;30:6094-105 pubmed publisher
    FLICE-inhibitory protein (FLIP) is an endogenous inhibitor of the signaling pathway triggered by the activation of death receptors...
  3. Yeh W, Itie A, Elia A, Ng M, Shu H, Wakeham A, et al. Requirement for Casper (c-FLIP) in regulation of death receptor-induced apoptosis and embryonic development. Immunity. 2000;12:633-42 pubmed
    b>Casper (c-FLIP) associates with FADD and caspase-8 in signaling complexes downstream of death receptors like Fas. We generated Casper-deficient mice and cells and noted a duality in the physiological functions of this molecule...
  4. Tseveleki V, Bauer J, Taoufik E, Ruan C, Leondiadis L, Haralambous S, et al. Cellular FLIP (long isoform) overexpression in T cells drives Th2 effector responses and promotes immunoregulation in experimental autoimmune encephalomyelitis. J Immunol. 2004;173:6619-26 pubmed
    Cellular FLIP (c-FLIP) is an endogenous inhibitor of death receptor-induced apoptosis through the caspase 8 pathway...
  5. Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, Steiner V, et al. Inhibition of death receptor signals by cellular FLIP. Nature. 1997;388:190-5 pubmed
    ..Here we report the characterization of an inhibitor of apoptosis, designated FLIP (for FLICE-inhibitory protein), which is predominantly expressed in muscle and lymphoid tissues...
  6. Goltsev Y, Kovalenko A, Arnold E, Varfolomeev E, Brodianskii V, Wallach D. CASH, a novel caspase homologue with death effector domains. J Biol Chem. 1997;272:19641-4 pubmed
    ..We report cloning of two splice variants of a novel protein, CASH, that contain two N-terminal death effector domains and can bind through them to each other, to MORT1/FADD, to CASP-..
  7. Zhang J, Chen Y, Huang Q, Cheng W, Kang Y, Shu L, et al. Nuclear localization of c-FLIP-L and its regulation of AP-1 activity. Int J Biochem Cell Biol. 2009;41:1678-84 pubmed publisher
    Cellular FLICE-like inhibitory protein (c-FLIP-L), similar in structure to caspase-8, is capable of blocking Fas- or other death receptors (DR)-mediated apoptosis through association with FADD in the DISC...
  8. Oberst A, Dillon C, Weinlich R, McCormick L, Fitzgerald P, Pop C, et al. Catalytic activity of the caspase-8-FLIP(L) complex inhibits RIPK3-dependent necrosis. Nature. 2011;471:363-7 pubmed publisher
    ..RIPK3-dependent necrosis without inducing apoptosis by functioning in a proteolytically active complex with FLICE-like inhibitory protein long (FLIP(L), also known as CFLAR), and this complex is required for the protective function.
  9. Chandrasekaran Y, McKee C, Ye Y, Richburg J. Influence of TRP53 status on FAS membrane localization, CFLAR (c-FLIP) ubiquitinylation, and sensitivity of GC-2spd (ts) cells to undergo FAS-mediated apoptosis. Biol Reprod. 2006;74:560-8 pubmed
    ..TRP53 may influence the ubiquitinylation and consequent proteosomal degradation of a negative regulator of FAS, CFLAR (L) (c-FLIP [L]), in human colon cancer cells...

More Information


  1. Antonangeli F, Petrungaro S, Coluccia P, Filippini A, Ziparo E, Giampietri C. Testis atrophy and reduced sperm motility in transgenic mice overexpressing c-FLIP(L). Fertil Steril. 2010;93:1407-14 pubmed publisher
    To study the effect of c-FLIP overexpression in testicular germ cells. A novel transgenic mouse model overexpressing the apoptotic modulator c-FLIP in the testis was generated. Animal facility and university research laboratory...
  2. Schattenberg J, Zimmermann T, Wörns M, Sprinzl M, Kreft A, Kohl T, et al. Ablation of c-FLIP in hepatocytes enhances death-receptor mediated apoptosis and toxic liver injury in vivo. J Hepatol. 2011;55:1272-80 pubmed publisher
    ..To examine the role of the caspase-8 homolog cellular FLICE-inhibitory protein (c-FLIP) in liver injury, we generated mice with hepatocyte specific deletion of c-FLIP...
  3. Schattenberg J, Nagel M, Kim Y, Kohl T, Wörns M, Zimmermann T, et al. Increased hepatic fibrosis and JNK2-dependent liver injury in mice exhibiting hepatocyte-specific deletion of cFLIP. Am J Physiol Gastrointest Liver Physiol. 2012;303:G498-506 pubmed publisher
    ..CCl(4)) and thioacetamide (TAA) were examined in mice exhibiting a hepatocyte-specific deletion of cFLIP (flip(-/-)). Acute liver injury from CCl(4) and TAA were enhanced in flip(-/-) mice...
  4. Varfolomeev E, Schuchmann M, Luria V, Chiannilkulchai N, Beckmann J, Mett I, et al. Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally. Immunity. 1998;9:267-76 pubmed
    ..These findings indicate that Caspase 8 plays a necessary and nonredundant role in death induction by several receptors of the TNF/NGF family and serves a vital role in embryonal development. ..
  5. Prows D, Hafertepen A, Winterberg A, Gibbons W, Liu C, Nick T. Genetic analysis of hyperoxic acute lung injury survival in reciprocal intercross mice. Physiol Genomics. 2007;30:271-81 pubmed
    ..QTL results confirmed that both parental strains contribute dominant resistance alleles to their offspring to determine individual HALI susceptibility. ..
  6. Skurk C, Maatz H, Kim H, Yang J, Abid M, Aird W, et al. The Akt-regulated forkhead transcription factor FOXO3a controls endothelial cell viability through modulation of the caspase-8 inhibitor FLIP. J Biol Chem. 2004;279:1513-25 pubmed
    FLICE-inhibitory protein (FLIP) is a homolog of caspase-8 that lacks catalytic activity and has been shown to be important in protecting endothelial cells from apoptosis...
  7. Dillon C, Oberst A, Weinlich R, Janke L, Kang T, Ben Moshe T, et al. Survival function of the FADD-CASPASE-8-cFLIP(L) complex. Cell Rep. 2012;1:401-7 pubmed
  8. Lee S, Yoon C, Byun S, Lee E, Lee S. The role of c-FLIP in cisplatin resistance of human bladder cancer cells. J Urol. 2013;189:2327-34 pubmed publisher
    ..Changes in cisplatin sensitivity by c-FLIP knockdown and related mechanisms in T24R2 cells were assessed using the Cell Counting Kit-8 assay (Dojindo ..
  9. Schile A, Garcia Fernandez M, Steller H. Regulation of apoptosis by XIAP ubiquitin-ligase activity. Genes Dev. 2008;22:2256-66 pubmed publisher
    ..This demonstrates a physiological requirement of XIAP ubiquitin-ligase activity for the inhibition of caspases and for tumor suppression in vivo. ..
  10. Wang X, Wang Y, Zhang J, Kim H, Ryter S, Choi A. FLIP protects against hypoxia/reoxygenation-induced endothelial cell apoptosis by inhibiting Bax activation. Mol Cell Biol. 2005;25:4742-51 pubmed
    ..Using mouse lung endothelial cells (MLEC), we examined the role of FLIP, an inhibitor of caspase 8, in hypoxia/reoxygenation-induced cell death...
  11. Wu Y, Kuo W, Wu Y, Yang K, Chen S, Jiang S, et al. Participation of c-FLIP in NLRP3 and AIM2 inflammasome activation. Cell Death Differ. 2014;21:451-61 pubmed publisher
    Cellular FLICE-inhibitory protein (c-FLIP) is an inhibitor of caspase-8 and is required for macrophage survival...
  12. Zhang H, Rosenberg S, Coffey F, He Y, Manser T, Hardy R, et al. A role for cFLIP in B cell proliferation and stress MAPK regulation. J Immunol. 2009;182:207-15 pubmed
    ..Cellular FLIP (cFLIP) is a homolog of caspase 8 and is also capable of binding to FADD...
  13. Yu Y, Iclozan C, Yamazaki T, Yang X, Anasetti C, Dong C, et al. Abundant c-Fas-associated death domain-like interleukin-1-converting enzyme inhibitory protein expression determines resistance of T helper 17 cells to activation-induced cell death. Blood. 2009;114:1026-8 pubmed publisher
    ..The resistance of Th17 cells to AICD reveals a novel mechanism to explain the high pathogenicity of Th17 cells in autoimmune diseases, and may also provide a rationale to generate tumor-specific Th17 cells for adoptive immunotherapy. ..
  14. Takai S, Nagaki M, Imao M, Kimura K, Kozawa O, Moriwaki H. Intrinsic resistance to TNF-alpha-induced hepatocyte apoptosis in ICR mice correlates with expression of a short form of c-FLIP. Lab Invest. 2007;87:572-81 pubmed
    ..Interestingly, the short form of cellular FLICE/caspase-8-inhibitory protein (c-FLIP(S)) was constitutively upregulated in ICR mice...
  15. Nakajima A, Komazawa Sakon S, Takekawa M, Sasazuki T, Yeh W, Yagita H, et al. An antiapoptotic protein, c-FLIPL, directly binds to MKK7 and inhibits the JNK pathway. EMBO J. 2006;25:5549-59 pubmed
    ..However, the detailed mechanisms are unclear. Here we show that cellular FLICE-inhibitory protein (c-FLIP) is rapidly lost in NF-kappaB activation-deficient, but not wild-type fibroblasts upon TNFalpha stimulation, ..
  16. Piao X, Komazawa Sakon S, Nishina T, Koike M, Piao J, Ehlken H, et al. c-FLIP maintains tissue homeostasis by preventing apoptosis and programmed necrosis. Sci Signal. 2012;5:ra93 pubmed publisher
    As a catalytically inactive homolog of caspase-8, a proapoptotic initiator caspase, c-FLIP blocks apoptosis by binding to and inhibiting caspase-8...
  17. Plaza Sirvent C, Schuster M, Neumann Y, Heise U, Pils M, Schulze Osthoff K, et al. c-FLIP Expression in Foxp3-Expressing Cells Is Essential for Survival of Regulatory T Cells and Prevention of Autoimmunity. Cell Rep. 2017;18:12-22 pubmed publisher that, compared to conventional T cells, Treg cells have a high apoptosis rate ex vivo correlating with low c-FLIP expression...
  18. Xiao C, Asselin E, Tsang B. Nuclear factor kappaB-mediated induction of Flice-like inhibitory protein prevents tumor necrosis factor alpha-induced apoptosis in rat granulosa cells. Biol Reprod. 2002;67:436-41 pubmed
    ..of the present studies was to examine the role and regulation of the antiapoptotic Flice-like inhibitory protein (FLIP) in rat granulosa cells by tumor necrosis factor alpha (TNFalpha) in vitro...
  19. Bouchet D, Tesson L, Menoret S, Charreau B, Mathieu P, Yagita H, et al. Differential sensitivity of endothelial cells of various species to apoptosis induced by gene transfer of Fas ligand: role of FLIP levels. Mol Med. 2002;8:612-23 pubmed
    ..In human ECs, levels of FLICE/caspase 8-inhibitory protein (FLIP) have been shown to control apoptosis mediated by Fas...
  20. Giampietri C, Petrungaro S, Conti S, Facchiano A, Filippini A, Ziparo E. c-Flip KO fibroblasts display lipid accumulation associated with endoplasmic reticulum stress. Biochim Biophys Acta. 2015;1851:929-36 pubmed publisher
    c-Flip proteins are well-known apoptosis modulators. They generally contribute to tissue homeostasis maintenance by inhibiting death-receptor-mediated cell death...
  21. Huo J, Xu S, Guo K, Zeng Q, Lam K. Genetic deletion of faim reveals its role in modulating c-FLIP expression during CD95-mediated apoptosis of lymphocytes and hepatocytes. Cell Death Differ. 2009;16:1062-70 pubmed publisher
    ..Detailed biochemical analyses further reveal the decreased expression of c-FLIP(L) and c-FLIP(R) in faim(-/-) thymocytes and increased association of caspase-8 with Fas in Fas-activated mutant ..
  22. Hashimoto M, Nakajima Shimada J, Aoki T. Trypanosoma cruzi posttranscriptionally up-regulates and exploits cellular FLIP for inhibition of death-inducing signal. Mol Biol Cell. 2005;16:3521-8 pubmed
    ..Here we demonstrate that the parasite dramatically up-regulates cellular FLICE inhibitory protein (c-FLIP), the only known mammalian inhibitor specific for death receptor signaling, in infected cells by an unusual, ..
  23. Wang P, Ji Y, Zhang X, Zhao L, Yan Z, Zhang P, et al. Targeting CASP8 and FADD-like apoptosis regulator ameliorates nonalcoholic steatohepatitis in mice and nonhuman primates. Nat Med. 2017;23:439-449 pubmed publisher
    ..Here we report that CASP8 and FADD-like apoptosis regulator (CFLAR) is a key suppressor of steatohepatitis and its metabolic disorders...
  24. Ranjan K, Pathak C. Expression of FADD and cFLIPL balances mitochondrial integrity and redox signaling to substantiate apoptotic cell death. Mol Cell Biochem. 2016;422:135-150 pubmed
    ..Altogether, our findings suggest that FADD and cFLIPL are important modulators of mitochondrial-associated apoptosis apart from the death receptor signaling. ..
  25. Golan Gerstl R, Wallach Dayan S, Zisman P, Cardoso W, Goldstein R, Breuer R. Cellular FLICE-like inhibitory protein deviates myofibroblast fas-induced apoptosis toward proliferation during lung fibrosis. Am J Respir Cell Mol Biol. 2012;47:271-9 pubmed publisher
    ..Cellular FLICE-like inhibitory protein (c-FLIP) is a regulator of cell death receptor-induced apoptosis in many cell types...
  26. Buck M, Chojkier M. C/EBPbeta associates with caspase 8 complex proteins and modulates apoptosis in hepatic stellate cells. J Clin Gastroenterol. 2007;41 Suppl 3:S295-9 pubmed
    ..Finally, we investigated whether C/EBPbeta is associated with the caspase 8 complex protein FLIP, a critical inhibitor of caspase 8...
  27. Misra R, Russell J, Koenig A, Hinshaw Makepeace J, Wen R, Wang D, et al. Caspase-8 and c-FLIPL associate in lipid rafts with NF-kappaB adaptors during T cell activation. J Biol Chem. 2007;282:19365-74 pubmed
    ..We observe that following TCR ligation, a small portion of total cellular caspase-8 and c-FLIP(L) rapidly migrate to lipid rafts where they associate in an active caspase complex...
  28. Tao R, Berkova Z, Wise J, Rezaeian A, Daniluk U, Ao X, et al. PMLRAR? binds to Fas and suppresses Fas-mediated apoptosis through recruiting c-FLIP in vivo. Blood. 2011;118:3107-18 pubmed publisher
    ..was demonstrated in U937/PR9 cells, human APL cells and transgenic mouse APL cells, in which PMLRAR? recruited c-FLIP(L/S) and excluded procaspase 8 from Fas death signaling complex...
  29. Huang Q, Perlman H, Birkett R, Doyle R, Fang D, Haines G, et al. CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis. Nat Commun. 2015;6:7086 pubmed publisher
    Dendritic cells (DCs) are critical for immune homeostasis. To target DCs, we generated a mouse line with Flip deficiency in cells that express cre under the CD11c promoter (CD11c-Flip-KO)...
  30. Giampietri C, Petrungaro S, Coluccia P, Antonangeli F, Giannakakis K, Faraggiana T, et al. c-Flip overexpression affects satellite cell proliferation and promotes skeletal muscle aging. Cell Death Dis. 2010;1:e38 pubmed publisher
    This study shows that forcing c-Flip overexpression in undifferentiated skeletal myogenic cells in vivo results in early aging muscle phenotype...
  31. Urresti J, Ruiz Meana M, Coccia E, Arévalo J, Castellano J, Fernández Sanz C, et al. Lifeguard Inhibits Fas Ligand-mediated Endoplasmic Reticulum-Calcium Release Mandatory for Apoptosis in Type II Apoptotic Cells. J Biol Chem. 2016;291:1221-34 pubmed publisher
    ..On the basis of our observations, we propose that there is a required step in the induction of type II apoptotic cell death that involves calcium mobilization from the ER and that this step is modulated by LFG. ..
  32. He M, He Y. c-FLIP protects T lymphocytes from apoptosis in the intrinsic pathway. J Immunol. 2015;194:3444-51 pubmed publisher
    ..Previous studies suggest that cellular caspase 8 (FLICE)-like inhibitory protein (c-FLIP) promotes cell survival in death receptor-induced apoptosis pathway in T lymphocytes...
  33. Dohrman A, Russell J, Cuenin S, Fortner K, Tschopp J, Budd R. Cellular FLIP long form augments caspase activity and death of T cells through heterodimerization with and activation of caspase-8. J Immunol. 2005;175:311-8 pubmed
    ..One logical candidate for this process is cellular FLIP long form (c-FLIP(L)), because it can block caspase-8 recruitment after Fas (CD95) ligation as well as directly ..
  34. McCubbrey A, Barthel L, Mohning M, Redente E, Mould K, Thomas S, et al. Deletion of c-FLIP from CD11bhi Macrophages Prevents Development of Bleomycin-induced Lung Fibrosis. Am J Respir Cell Mol Biol. 2018;58:66-78 pubmed publisher
    ..we targeted deletion of the antiapoptotic protein cellular FADD-like IL-1?-converting enzyme-inhibitory protein (c-FLIP) to CD11bhi M?. Upon loss of c-FLIP, CD11bhi M? became susceptible to cell death...
  35. Taoufik E, Valable S, Müller G, Roberts M, Divoux D, Tinel A, et al. FLIP(L) protects neurons against in vivo ischemia and in vitro glucose deprivation-induced cell death. J Neurosci. 2007;27:6633-46 pubmed
    ..long isoform of cellular Fas-associated death domain-like interleukin-1-beta-converting enzyme-inhibitory protein (FLIP(L))...
  36. Oehme I, Neumann F, Bösser S, Zörnig M. Transgenic overexpression of the Caspase-8 inhibitor FLIP(short) leads to impaired T cell proliferation and an increased memory T cell pool after staphylococcal enterotoxin B injection. Eur J Immunol. 2005;35:1240-9 pubmed
    The cellular homologues of the viral anti-apoptotic v-FLIP proteins exist as a long (c-FLIP(L)) and a short (c-FLIP(S)) splice variant...
  37. Moumen A, Ieraci A, Patanè S, Sole C, Comella J, Dono R, et al. Met signals hepatocyte survival by preventing Fas-triggered FLIP degradation in a PI3k-Akt-dependent manner. Hepatology. 2007;45:1210-7 pubmed
    ..of caspase-8 activation and cell death is a protective mechanism modulated by the FLICE-Like Inhibitory Protein (FLIP)...
  38. Zhang N, Hopkins K, He Y. The long isoform of cellular FLIP is essential for T lymphocyte proliferation through an NF-kappaB-independent pathway. J Immunol. 2008;180:5506-11 pubmed
    Although the long isoform of cellular FLIP (c-FLIP(L)) has been implicated in TCR-mediated signaling, its role in T cell proliferation remains controversial...
  39. Lin Y, Yao P, Richburg J. FasL gene-deficient mice display a limited disruption in spermatogenesis and inhibition of mono-(2-ethylhexyl) phthalate-induced germ cell apoptosis. Toxicol Sci. 2010;114:335-45 pubmed publisher
    ..cell toxicant, unexpectedly caused a rapid decrease in the germ cell AI that paralleled increased levels of the CFLAR (c-FLIP) protein, a known inhibitor of death receptor signaling...
  40. Giampietri C, Petrungaro S, Coluccia P, Antonangeli F, Paone A, Padula F, et al. c-Flip(L) is expressed in undifferentiated mouse male germ cells. FEBS Lett. 2006;580:6109-14 pubmed
    ..Therefore pro- and anti-apoptotic proteins are essential to regulate testis physiology. c-Flip(L) is a known inhibitor of caspase 8/10 activity; in this study its perinatal expression in mouse male germ cells ..
  41. Telieps T, Ewald F, Gereke M, Annemann M, Rauter Y, Schuster M, et al. Cellular-FLIP, Raji isoform (c-FLIP R) modulates cell death induction upon T-cell activation and infection. Eur J Immunol. 2013;43:1499-510 pubmed publisher
    ..Cellular-FLIP (c-FLIP) proteins inhibit apoptosis directly at the death-inducing signaling complex of death receptors, such as ..
  42. Xiao J, Moon M, Yan L, Nian M, Zhang Y, Liu C, et al. Cellular FLICE-inhibitory protein protects against cardiac remodelling after myocardial infarction. Basic Res Cardiol. 2012;107:239 pubmed publisher
    ..Thus, cFLIP gene delivery shows promise as a clinically powerful and novel therapeutic strategy for the treatment of heart failure after MI. ..
  43. Newton K, Dugger D, Wickliffe K, Kapoor N, de Almagro M, Vucic D, et al. Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis. Science. 2014;343:1357-60 pubmed publisher
    ..Our data indicate that the kinase activity of RIPK3 is essential for necroptosis but also governs whether a cell activates caspase-8 and dies by apoptosis. ..
  44. Tseveleki V, Tsagozis P, Koutsoni O, Dotsika E, Probert L. Cellular FLIP long isoform transgenic mice overcome inherent Th2-biased immune responses to efficiently resolve Leishmania major infection. Int Immunol. 2007;19:1183-9 pubmed
    c-FLIP(L) expression in T cells is required for mounting effective T cell responses and can also be critical for effector T cell differentiation, as has recently been shown by a number of in vivo studies in conditional knockout and ..
  45. Zhu J, Giaisi M, Kohler R, Muller W, Mühleisen A, Proksch P, et al. Rocaglamide sensitizes leukemic T cells to activation-induced cell death by differential regulation of CD95L and c-FLIP expression. Cell Death Differ. 2009;16:1289-99 pubmed publisher
    ..preferentially promotes activation-induced cell death in malignant T cells by differential regulation of c-FLIP and CD95L expression...
  46. Gehrke N, Garcia Bardon D, Mann A, Schad A, Alt Y, Wörns M, et al. Acute organ failure following the loss of anti-apoptotic cellular FLICE-inhibitory protein involves activation of innate immune receptors. Cell Death Differ. 2015;22:826-37 pubmed publisher
    ..These results encourage the development of organ-specific anti-apoptotic and anti-inflammatory therapies in acute organ failure. ..
  47. Fang Y, Braley Mullen H. Cultured murine thyroid epithelial cells expressing transgenic Fas-associated death domain-like interleukin-1beta converting enzyme inhibitory protein are protected from fas-mediated apoptosis. Endocrinology. 2008;149:3321-9 pubmed publisher
    The antiapoptotic molecule Fas-associated death domain-like IL-1beta-converting enzyme inhibitory protein (FLIP) inhibits Fas-mediated apoptosis by blocking activation of caspase-8...
  48. Zhang N, He Y. An essential role for c-FLIP in the efficient development of mature T lymphocytes. J Exp Med. 2005;202:395-404 pubmed
    ..We show that cellular FLICE-like inhibitory protein (c-FLIP), a procaspase-8-like apoptotic regulator, plays an essential role in the efficient development of mature T ..
  49. Chastagner P, Reddy J, Theze J. Lymphoadenopathy in IL-2-deficient mice: further characterization and overexpression of the antiapoptotic molecule cellular FLIP. J Immunol. 2002;169:3644-51 pubmed
    ..Because the apoptosis inhibitor FLIP has been shown in vitro to participate in the IL-2 control of activation-induced cell death, we analyze its ..
  50. Behnke J, Iraqi F, Mugambi J, Clifford S, Nagda S, Wakelin D, et al. High resolution mapping of chromosomal regions controlling resistance to gastrointestinal nematode infections in an advanced intercross line of mice. Mamm Genome. 2006;17:584-97 pubmed
    ..4 cM). Strong candidate genes for the QTL position on Chromosome 1 include genes known to be involved in regulating immune responses and on Chromosome 17 genes within the MHC, notably the Class II molecules and tumor necrosis factor. ..
  51. Koenig A, Buskiewicz I, Fortner K, Russell J, Asaoka T, He Y, et al. The c-FLIPL cleavage product p43FLIP promotes activation of extracellular signal-regulated kinase (ERK), nuclear factor ?B (NF-?B), and caspase-8 and T cell survival. J Biol Chem. 2014;289:1183-91 pubmed publisher
    ..The caspase-8 paralogue c-FLIP is a good candidate for a molecular rheostat of caspase-8 activity...
  52. Kim Y, Park H, Jeoung D. CAGE, a cancer/testis antigen, induces c-FLIP(L) and Snail to enhance cell motility and increase resistance to an anti-cancer drug. Biotechnol Lett. 2009;31:945-52 pubmed publisher
    ..CAGE was shown to protect cells against celastrol, an anti-cancer agent. Celastrol-resistant B16F10 melanoma cells had a higher expression level of c-FLIP(L) and Snail as compared with a sensitive cell line.
  53. Ram D, Ilyukha V, Volkova T, Buzdin A, Tai A, Smirnova I, et al. Balance between short and long isoforms of cFLIP regulates Fas-mediated apoptosis in vivo. Proc Natl Acad Sci U S A. 2016;113:1606-11 pubmed publisher
    ..MSM loci controlling resistance to Fas-mediated death, including the caspase 8- and FADD-like apoptosis regulator (Cflar) locus encoding cFLIP...
  54. Giampietri C, Petrungaro S, Klinger F, Coluccia P, Paone A, Vivarelli E, et al. c-Flip expression and function in fetal mouse gonocytes. FASEB J. 2006;20:124-6 pubmed
    ..We evaluated the expression and function of c-Flip, an apoptosis inhibitor known to interfere with the proapoptotic Fas-signaling pathway in a variety of cell types, ..
  55. 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. ..
  56. Zhang N, Hopkins K, He Y. c-FLIP protects mature T lymphocytes from TCR-mediated killing. J Immunol. 2008;181:5368-73 pubmed
    Although c-FLIP has been identified as an important player in the extrinsic (death receptor-induced) apoptosis pathway, its endogenous function in mature T lymphocytes remains undefined...
  57. Huang Q, Perlman H, Huang Z, Birkett R, Kan L, Agrawal H, et al. FLIP: a novel regulator of macrophage differentiation and granulocyte homeostasis. Blood. 2010;116:4968-77 pubmed publisher
    b>FLIP is a well-established suppressor of death receptor-mediated apoptosis. To define its essential in vivo role in myeloid cells, we generated and characterized mice with Flip conditionally deleted in the myeloid lineage...
  58. Ewald F, Annemann M, Pils M, Plaza Sirvent C, Neff F, Erck C, et al. Constitutive expression of murine c-FLIPR causes autoimmunity in aged mice. Cell Death Dis. 2014;5:e1168 pubmed publisher
    ..The only short murine c-FLIP splice variant is c-FLIPRaji (c-FLIPR)...
  59. Llobet D, Eritja N, Domingo M, Bergada L, Mirantes C, Santacana M, et al. KSR1 is overexpressed in endometrial carcinoma and regulates proliferation and TRAIL-induced apoptosis by modulating FLIP levels. Am J Pathol. 2011;178:1529-43 pubmed publisher
    ..Sensitization to TRAIL and agonistic anti-Fas antibody was caused by down-regulation of FLIP (FLICE-inhibitory protein)...
  60. Kohl T, Gehrke N, Schad A, Nagel M, Wörns M, Sprinzl M, et al. Diabetic liver injury from streptozotocin is regulated through the caspase-8 homolog cFLIP involving activation of JNK2 and intrahepatic immunocompetent cells. Cell Death Dis. 2013;4:e712 pubmed publisher
    ..In mice lacking cFLIP in hepatocytes (flip(-/-)), loss of insulin following streptozotocin treatment resulted in caspase- and c-Jun N-terminal kinase (JNK)-..
  61. Hinshaw Makepeace J, Huston G, Fortner K, Russell J, Holoch D, Swain S, et al. c-FLIP(S) reduces activation of caspase and NF-kappaB pathways and decreases T cell survival. Eur J Immunol. 2008;38:54-63 pubmed
    ..A likely candidate is cellular FLIP (c-FLIP), an enzymatically inert caspase-8 homologue...
  62. Huang Y, Wu L, Wu J, Li Y, Hou L. Cellular FLICE-like inhibitory protein protects against cardiac hypertrophy by blocking ASK1/p38 signaling in mice. Mol Cell Biochem. 2014;397:87-95 pubmed publisher
    Cellular FLICE-like inhibitory protein (Flip) is a negative regulator of nuclear factor ?B signaling which has been shown previously to complicate with cardiac hypertrophy...
  63. Hainsworth A, Bermpohl D, Webb T, Darwish R, Fiskum G, Qiu J, et al. Expression of cellular FLICE inhibitory proteins (cFLIP) in normal and traumatic murine and human cerebral cortex. J Cereb Blood Flow Metab. 2005;25:1030-40 pubmed
    ..The data suggest differential spatial and temporal regulation of cFLIP-alpha and cFLIP-delta expression that may influence the magnitude of cell death and further implicate programmed mechanisms of cell death after TBI. ..
  64. Roué G, Perez Galan P, Lopez Guerra M, Villamor N, Campo E, Colomer D. Selective inhibition of IkappaB kinase sensitizes mantle cell lymphoma B cells to TRAIL by decreasing cellular FLIP level. J Immunol. 2007;178:1923-30 pubmed
    ..TRAIL was closely linked to the activity of the NF-kappaB p50 factor and to the consequent expression of cellular FLIP (c-FLIP), which accumulated into the TRAIL-dependent complex in resistant cells...
  65. Lim E, Park D, Lee J, Lee C, Bae Y, Hwang Y, et al. Toll-like receptor 9-mediated inhibition of apoptosis occurs through suppression of FoxO3a activity and induction of FLIP expression. Exp Mol Med. 2010;42:712-20 pubmed
    ..prevented apoptosis induced by serum deprivation through increased expression of FLICE-like inhibitory protein (FLIP). CpG ODN-mediated anti-apoptosis depended on the TLR9-Akt-FoxO3a signaling pathway...
  66. Matsumori Y, Northington F, Hong S, Kayama T, Sheldon R, Vexler Z, et al. Reduction of caspase-8 and -9 cleavage is associated with increased c-FLIP and increased binding of Apaf-1 and Hsp70 after neonatal hypoxic/ischemic injury in mice overexpressing Hsp70. Stroke. 2006;37:507-12 pubmed
    ..Increased cellular Fas-associated death domain-like interleukin-1beta-converting enzyme inhibitory protein (FLIP) expression and decreased caspase-8 cleavage were also observed in Hsp70 Tg compared with Wt mice 24 hours after H/..
  67. Gordy C, Pua H, Sempowski G, He Y. Regulation of steady-state neutrophil homeostasis by macrophages. Blood. 2011;117:618-29 pubmed publisher
    ..By conditionally deleting the antiapoptotic gene cellular FLICE-like inhibitory protein (C-FLIP) in myeloid cells, we have generated a novel mouse model deficient in marginal zone and bone marrow stromal ..
  68. Coffey F, Manser T. Expression of cellular FLIP by B cells is required for their participation in an immune response. J Immunol. 2010;184:4871-9 pubmed publisher
    High levels of the Fas-signaling antagonist cellular FLIP (cFLIP) in germinal center (GC) B cells suggests an important role for this factor during this stage of the T cell-dependent B cell immune response...
  69. Hill N, Lyons P, Armitage N, Todd J, Wicker L, Peterson L. NOD Idd5 locus controls insulitis and diabetes and overlaps the orthologous CTLA4/IDDM12 and NRAMP1 loci in humans. Diabetes. 2000;49:1744-7 pubmed
    ..4-cM interval. Idd5.1 is in the proximal 1.5-cM portion of the interval and contains the candidates Casp8, Cflar (FLIP), Cd28, and Cd152 (CTLA4). Idd5.1 overlaps the orthologous CTLA4/IDDM12 locus in humans. Idd5...
  70. Bossaller L, Chiang P, Schmidt Lauber C, Ganesan S, Kaiser W, Rathinam V, et al. Cutting edge: FAS (CD95) mediates noncanonical IL-1? and IL-18 maturation via caspase-8 in an RIP3-independent manner. J Immunol. 2012;189:5508-12 pubmed publisher
    ..Hence, Fas controls a novel noncanonical IL-1? activation pathway in myeloid cells, which could play an essential role in inflammatory processes, tumor surveillance, and control of infectious diseases. ..
  71. Newton K, Wickliffe K, Maltzman A, Dugger D, Strasser A, Pham V, et al. RIPK1 inhibits ZBP1-driven necroptosis during development. Nature. 2016;540:129-133 pubmed publisher
    ..Collectively, these findings indicate that the RHIM of RIPK1 is critical for preventing ZBP1/RIPK3/MLKL-dependent necroptosis during development. ..
  72. Ye J, Llorian M, Cardona M, Rongvaux A, Moubarak R, Comella J, et al. A pathway involving HDAC5, cFLIP and caspases regulates expression of the splicing regulator polypyrimidine tract binding protein in the heart. J Cell Sci. 2013;126:1682-91 pubmed publisher
  73. Moujalled D, Cook W, Lluis J, Khan N, Ahmed A, Callus B, et al. In mouse embryonic fibroblasts, neither caspase-8 nor cellular FLICE-inhibitory protein (FLIP) is necessary for TNF to activate NF-?B, but caspase-8 is required for TNF to cause cell death, and induction of FLIP by NF-?B is required to prevent it. Cell Death Differ. 2012;19:808-15 pubmed publisher
    ..To determine the roles of FLICE-inhibitory protein (FLIP) and caspase-8 in TNF-induced activation of NF-?B and apoptosis, we used mouse embryonic fibroblasts derived from ..
  74. Zhuge B, Li G. MiR-150 deficiency ameliorated hepatosteatosis and insulin resistance in nonalcoholic fatty liver disease via targeting CASP8 and FADD-like apoptosis regulator. Biochem Biophys Res Commun. 2017;494:687-692 pubmed publisher
    ..Further, we identified that CFLAR is a direct downstream target of miR-150...