The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

CFLAR  -  CASP8 and FADD-like apoptosis regulator

Homo sapiens

Synonyms: CASH, CASP8AP1, CLARP, Caspase homolog, Caspase-eight-related protein, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of CFLAR


Psychiatry related information on CFLAR

  • BACKGROUND: Flame injury confers significant physical and psychologic stress on burn patients [7].
  • Commentary on McSherry W, Cash K & Ross L (2004) Meaning of spirituality: implications for nursing practice. Journal of Clinical Nursing 13, 934-941 [8].
  • Body image, as measured by the Appearance Evaluation and Body Areas Satisfaction scales of the Multidimensional Body-Self Relations Questionnaire (T.F. Cash, 1994b), was assessed in 59 obese women before, during, and after 48 weeks of weight loss treatment [9].
  • Mental health forum. 1. Cash on delivery [10].
  • Given evidence that questionnaire assessment of panic results in substantial false positives (Brown & Cash, 1989, Journal of Anxiety Disorders, 3, 139-148), it was hypothesized that familial aggregation differences could be largely attributable to this phenomenon as well [11].

High impact information on CFLAR


Chemical compound and disease context of CFLAR


Biological context of CFLAR


Anatomical context of CFLAR


Associations of CFLAR with chemical compounds

  • However, both caspase 8 and caspase 10 recruitment and processing within the TRAIL death-inducing signaling complex (DISC) were greater in GCDCA-treated cells whereas recruitment of cFLIP long and short was reduced [23].
  • Death receptors trigger apoptosis by activating the apical cysteine proteases caspase-8 and -10 within a death-inducing signaling complex (DISC). c-FLIP (cellular FLICE inhibitory protein) is an enzymatically inactive relative of caspase-8 and -10 that binds to the DISC [24].
  • Cross-resistance to death ligand-induced apoptosis in cisplatin-selected HeLa cells associated with overexpression of DDB2 and subsequent induction of cFLIP [25].
  • Cell death was only observed in the presence of cycloheximide or after a pulse through CD3 or CD59, correlating with a net reduction in cellular Fas-associated death domain-like IL-1beta-converting enzyme-inhibitory protein long (c-FLIPL) and c-FLIPS expression [26].
  • In contrast, in response to doxorubicin, levels of c-FLIP, particularly FLIP(S), decreased in all cell lines tested [14].

Physical interactions of CFLAR

  • In addition, MRIT simultaneously and independently interacts with BclXL and FLICE in mammalian cells [20].
  • Moreover, we show that a cellular membrane permeable version of the peptide corresponding to the DR5 binding domain of c-FLIP induces apoptosis in mammalian cells [27].
  • CASPER is an increment rule-based approach which uses chemical shifts of the free reducing monosaccharides which are altered according to attached residues of an oligo- or polysaccharide sequence [28].

Regulatory relationships of CFLAR

  • In stably transfected BJAB cells, c-FLIP blocks caspase-8 activation at the DISC and thereby inhibits CD95-mediated apoptosis [29].
  • Accordingly, the elimination of cFLIP by antisense oligonucleotides suppresses DDB2 protection [25].
  • After JO2 exposure, CFLAR (L) protein levels were enhanced only at the nonpermissive TRP53 temperature (37 degrees C) while real-time PCR results indicated an absence of Cflar (L) mRNA changes in GC-2 cells regardless of the temperature [30].
  • In this study, we demonstrated that TNF-alpha-induced cell proliferation is achieved through the c-FLIP [31].
  • ASC-mediated NF-kappaB activation leading to interleukin-8 production requires caspase-8 and is inhibited by CLARP [32].

Other interactions of CFLAR


Analytical, diagnostic and therapeutic context of CFLAR


  1. Expression of the cellular FLICE-inhibitory protein (c-FLIP) protects Hodgkin's lymphoma cells from autonomous Fas-mediated death. Dutton, A., O'Neil, J.D., Milner, A.E., Reynolds, G.M., Starczynski, J., Crocker, J., Young, L.S., Murray, P.G. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  2. Cell death attenuation by 'Usurpin', a mammalian DED-caspase homologue that precludes caspase-8 recruitment and activation by the CD-95 (Fas, APO-1) receptor complex. Rasper, D.M., Vaillancourt, J.P., Hadano, S., Houtzager, V.M., Seiden, I., Keen, S.L., Tawa, P., Xanthoudakis, S., Nasir, J., Martindale, D., Koop, B.F., Peterson, E.P., Thornberry, N.A., Huang, J., MacPherson, D.P., Black, S.C., Hornung, F., Lenardo, M.J., Hayden, M.R., Roy, S., Nicholson, D.W. Cell Death Differ. (1998) [Pubmed]
  3. Loss of expression of death-inducing signaling complex (DISC) components in lung cancer cell lines and the influence of MYC amplification. Shivapurkar, N., Reddy, J., Matta, H., Sathyanarayana, U.G., Huang, C.X., Toyooka, S., Minna, J.D., Chaudhary, P.M., Gazdar, A.F. Oncogene (2002) [Pubmed]
  4. Histone deacetylase inhibition by valproic acid down-regulates c-FLIP/CASH and sensitizes hepatoma cells towards CD95- and TRAIL receptor-mediated apoptosis and chemotherapy. Schuchmann, M., Schulze-Bergkamen, H., Fleischer, B., Schattenberg, J.M., Siebler, J., Weinmann, A., Teufel, A., Wörns, M., Fischer, T., Strand, S., Lohse, A.W., Galle, P.R. Oncol. Rep. (2006) [Pubmed]
  5. Downregulation of c-FLIP sensitizes DU145 prostate cancer cells to Fas-mediated apoptosis. Hyer, M.L., Sudarshan, S., Kim, Y., Reed, J.C., Dong, J.Y., Schwartz, D.A., Norris, J.S. Cancer Biol. Ther. (2002) [Pubmed]
  6. c-FLIP: a key regulator of colorectal cancer cell death. Wilson, T.R., McLaughlin, K.M., McEwan, M., Sakai, H., Rogers, K.M., Redmond, K.M., Johnston, P.G., Longley, D.B. Cancer Res. (2007) [Pubmed]
  7. Application of Rehabilitation Ethics to a Selected Burn Patient Population's Perspective. Brewster, L.P., Bennett, B.K., Gamelli, R.L. J. Am. Coll. Surg. (2006) [Pubmed]
  8. Commentary on McSherry W, Cash K & Ross L (2004) Meaning of spirituality: implications for nursing practice. Journal of Clinical Nursing 13, 934-941. Whitehead, D. Journal of clinical nursing. (2006) [Pubmed]
  9. Body image in obese women before, during, and after weight loss treatment. Foster, G.D., Wadden, T.A., Vogt, R.A. Health psychology : official journal of the Division of Health Psychology, American Psychological Association. (1997) [Pubmed]
  10. Mental health forum. 1. Cash on delivery. Chapman, S. Nursing mirror. (1983) [Pubmed]
  11. Familial aggregation of panic in nonclinical panickers. Brown, T.A. Behaviour research and therapy. (1994) [Pubmed]
  12. Casper is a FADD- and caspase-related inducer of apoptosis. Shu, H.B., Halpin, D.R., Goeddel, D.V. Immunity (1997) [Pubmed]
  13. c-FLIP mediates resistance of Hodgkin/Reed-Sternberg cells to death receptor-induced apoptosis. Mathas, S., Lietz, A., Anagnostopoulos, I., Hummel, F., Wiesner, B., Janz, M., Jundt, F., Hirsch, B., Jöhrens-Leder, K., Vornlocher, H.P., Bommert, K., Stein, H., Dörken, B. J. Exp. Med. (2004) [Pubmed]
  14. Doxorubicin pretreatment sensitizes prostate cancer cell lines to TRAIL induced apoptosis which correlates with the loss of c-FLIP expression. Kelly, M.M., Hoel, B.D., Voelkel-Johnson, C. Cancer Biol. Ther. (2002) [Pubmed]
  15. Depsipeptide (FR901228) induces histone acetylation and inhibition of histone deacetylase in chronic lymphocytic leukemia cells concurrent with activation of caspase 8-mediated apoptosis and down-regulation of c-FLIP protein. Aron, J.L., Parthun, M.R., Marcucci, G., Kitada, S., Mone, A.P., Davis, M.E., Shen, T., Murphy, T., Wickham, J., Kanakry, C., Lucas, D.M., Reed, J.C., Grever, M.R., Byrd, J.C. Blood (2003) [Pubmed]
  16. Cellular FLICE-Inhibitory Protein Down-regulation Contributes to Celecoxib-Induced Apoptosis in Human Lung Cancer Cells. Liu, X., Yue, P., Sch??nthal, A.H., Khuri, F.R., Sun, S.Y. Cancer Res. (2006) [Pubmed]
  17. c-FLIP inhibits chemotherapy-induced colorectal cancer cell death. Longley, D.B., Wilson, T.R., McEwan, M., Allen, W.L., McDermott, U., Galligan, L., Johnston, P.G. Oncogene (2006) [Pubmed]
  18. c-FLIP efficiently rescues TRAF-2-/- cells from TNF-induced apoptosis. Guiet, C., Silvestri, E., De Smaele, E., Franzoso, G., Vito, P. Cell Death Differ. (2002) [Pubmed]
  19. CLARP, a death effector domain-containing protein interacts with caspase-8 and regulates apoptosis. Inohara, N., Koseki, T., Hu, Y., Chen, S., Núñez, G. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  20. MRIT, a novel death-effector domain-containing protein, interacts with caspases and BclXL and initiates cell death. Han, D.K., Chaudhary, P.M., Wright, M.E., Friedman, C., Trask, B.J., Riedel, R.T., Baskin, D.G., Schwartz, S.M., Hood, L. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  21. Phosphatidylinositide 3-kinase priming couples c-FLIP to T cell activation. Fang, L.W., Tai, T.S., Yu, W.N., Liao, F., Lai, M.Z. J. Biol. Chem. (2004) [Pubmed]
  22. Expression of cellular FLICE-inhibitory protein in human coronary arteries and in a rat vascular injury model. Imanishi, T., McBride, J., Ho, Q., O'Brien, K.D., Schwartz, S.M., Han, D.K. Am. J. Pathol. (2000) [Pubmed]
  23. Bile acids stimulate cFLIP phosphorylation enhancing TRAIL-mediated apoptosis. Higuchi, H., Yoon, J.H., Grambihler, A., Werneburg, N., Bronk, S.F., Gores, G.J. J. Biol. Chem. (2003) [Pubmed]
  24. Selective knockdown of the long variant of cellular FLICE inhibitory protein augments death receptor-mediated caspase-8 activation and apoptosis. Sharp, D.A., Lawrence, D.A., Ashkenazi, A. J. Biol. Chem. (2005) [Pubmed]
  25. Cross-resistance to death ligand-induced apoptosis in cisplatin-selected HeLa cells associated with overexpression of DDB2 and subsequent induction of cFLIP. Sun, C.L., Chao, C.C. Mol. Pharmacol. (2005) [Pubmed]
  26. Down-regulation of normal human T cell blast activation: roles of APO2L/TRAIL, FasL, and c- FLIP, Bim, or Bcl-x isoform expression. Bosque, A., Pardo, J., Martínez-Lorenzo, M.J., Iturralde, M., Marzo, I., Piñeiro, A., Alava, M.A., Naval, J., Anel, A. J. Leukoc. Biol. (2005) [Pubmed]
  27. Fas-associated protein with death domain (FADD)-independent recruitment of c-FLIPL to death receptor 5. Jin, T.G., Kurakin, A., Benhaga, N., Abe, K., Mohseni, M., Sandra, F., Song, K., Kay, B.K., Khosravi-Far, R. J. Biol. Chem. (2004) [Pubmed]
  28. GlyNest and CASPER: two independent approaches to estimate 1H and 13C NMR shifts of glycans available through a common web-interface. Loss, A., Stenutz, R., Schwarzer, E., von der Lieth, C.W. Nucleic Acids Res. (2006) [Pubmed]
  29. The role of c-FLIP in modulation of CD95-induced apoptosis. Scaffidi, C., Schmitz, I., Krammer, P.H., Peter, M.E. J. Biol. Chem. (1999) [Pubmed]
  30. Influence of TRP53 status on FAS membrane localization, CFLAR (c-FLIP) ubiquitinylation, and sensitivity of GC-2spd (ts) cells to undergo FAS-mediated apoptosis. Chandrasekaran, Y., McKee, C.M., Ye, Y., Richburg, J.H. Biol. Reprod. (2006) [Pubmed]
  31. Alternative splicing variants of c-FLIP transduce the differential signal through the Raf or TRAF2 in TNF-induced cell proliferation. Park, S.J., Kim, Y.Y., Ju, J.W., Han, B.G., Park, S.I., Park, B.J. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  32. ASC-mediated NF-kappaB activation leading to interleukin-8 production requires caspase-8 and is inhibited by CLARP. Hasegawa, M., Imamura, R., Kinoshita, T., Matsumoto, N., Masumoto, J., Inohara, N., Suda, T. J. Biol. Chem. (2005) [Pubmed]
  33. FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis. Srinivasula, S.M., Ahmad, M., Ottilie, S., Bullrich, F., Banks, S., Wang, Y., Fernandes-Alnemri, T., Croce, C.M., Litwack, G., Tomaselli, K.J., Armstrong, R.C., Alnemri, E.S. J. Biol. Chem. (1997) [Pubmed]
  34. Selective inhibition of FLICE-like inhibitory protein expression with small interfering RNA oligonucleotides is sufficient to sensitize tumor cells for TRAIL-induced apoptosis. Siegmund, D., Hadwiger, P., Pfizenmaier, K., Vornlocher, H.P., Wajant, H. Mol. Med. (2002) [Pubmed]
  35. A Novel Strategy for Preventing Human CD8(+) Cytotoxic T Lymphocyte-Mediated Cytotoxicity Against Pig Endothelial Cells by Overexpression of Pig Cellular FLICE-like Inhibitory Protein (c-FLIP) Gene. Tanemura, M., Saga, A., Kawamoto, K., Matsuda-Minehata, F., Manabe, N., Deguchi, T., Nishida, T., Sawa, Y., Ito, T. Transplant. Proc. (2006) [Pubmed]
  36. A functional role of flip in conferring resistance of Crohn's disease lamina propria lymphocytes to FAS-mediated apoptosis. Monteleone, I., Monteleone, G., Fina, D., Caruso, R., Petruzziello, C., Calabrese, E., Biancone, L., Pallone, F. Gastroenterology (2006) [Pubmed]
WikiGenes - Universities