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Pathway Description
FAS signaling pathway ( CD95 )
Homo sapiens
Protein Pathway
Created: 2018-08-01
Last Updated: 2019-08-16
Fas ligand is a transmembrane protein part of the tumor necrosis factor (TNF) family. It plays a role in inducing apoptosis and is an important regulator of the immune system. Fas ligand signals through the Fas receptor on target cells. Fas ligand binds to the receptor and forms the death-inducing signalling complex, including the Fas-associated death domain, death-domain associated protein, and caspase-10. Caspases are synthesized as inactive pro-caspases. Caspases are are proteases that cleave their substrates. Caspase-8 is an initiator caspase that is activated in response to pro-apoptotic stimulus and causes a cascade of further caspase activity by cleaving and activating effector caspases, like caspases -3 and -7. Once activated, caspases -3 and -7 cleave downstream proteins. Caspase-8 activity is regulated by CASP8 and FADD-like apoptosis regulator. Kinases activate mitogen-activated protein kinases which activate pro-apoptotic JNK activity.
References
FAS signaling pathway ( CD95 ) References
Houston A, O'Connell J: The Fas signalling pathway and its role in the pathogenesis of cancer. Curr Opin Pharmacol. 2004 Aug;4(4):321-6. doi: 10.1016/j.coph.2004.03.008.
Pubmed: 15251123
Wajant H: The Fas signaling pathway: more than a paradigm. Science. 2002 May 31;296(5573):1635-6. doi: 10.1126/science.1071553.
Pubmed: 12040174
https://cgap.nci.nih.gov/Pathways/BioCarta/h_fasPathway
Alderson MR, Tough TW, Davis-Smith T, Braddy S, Falk B, Schooley KA, Goodwin RG, Smith CA, Ramsdell F, Lynch DH: Fas ligand mediates activation-induced cell death in human T lymphocytes. J Exp Med. 1995 Jan 1;181(1):71-7. doi: 10.1084/jem.181.1.71.
Pubmed: 7528780
Takahashi T, Tanaka M, Inazawa J, Abe T, Suda T, Nagata S: Human Fas ligand: gene structure, chromosomal location and species specificity. Int Immunol. 1994 Oct;6(10):1567-74. doi: 10.1093/intimm/6.10.1567.
Pubmed: 7826947
Mita E, Hayashi N, Iio S, Takehara T, Hijioka T, Kasahara A, Fusamoto H, Kamada T: Role of Fas ligand in apoptosis induced by hepatitis C virus infection. Biochem Biophys Res Commun. 1994 Oct 28;204(2):468-74. doi: 10.1006/bbrc.1994.2483.
Pubmed: 7980502
Itoh N, Yonehara S, Ishii A, Yonehara M, Mizushima S, Sameshima M, Hase A, Seto Y, Nagata S: The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell. 1991 Jul 26;66(2):233-43. doi: 10.1016/0092-8674(91)90614-5.
Pubmed: 1713127
Oehm A, Behrmann I, Falk W, Pawlita M, Maier G, Klas C, Li-Weber M, Richards S, Dhein J, Trauth BC, et al.: Purification and molecular cloning of the APO-1 cell surface antigen, a member of the tumor necrosis factor/nerve growth factor receptor superfamily. Sequence identity with the Fas antigen. J Biol Chem. 1992 May 25;267(15):10709-15.
Pubmed: 1375228
Liu C, Cheng J, Mountz JD: Differential expression of human Fas mRNA species upon peripheral blood mononuclear cell activation. Biochem J. 1995 Sep 15;310 ( Pt 3):957-63. doi: 10.1042/bj3100957.
Pubmed: 7575433
Ryu SW, Chae SK, Lee KJ, Kim E: Identification and characterization of human Fas associated factor 1, hFAF1. Biochem Biophys Res Commun. 1999 Aug 27;262(2):388-94. doi: 10.1006/bbrc.1999.1217.
Pubmed: 10462485
Lai CH, Chou CY, Ch'ang LY, Liu CS, Lin W: Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics. Genome Res. 2000 May;10(5):703-13. doi: 10.1101/gr.10.5.703.
Pubmed: 10810093
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Pubmed: 16710414
Chinnaiyan AM, O'Rourke K, Tewari M, Dixit VM: FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell. 1995 May 19;81(4):505-12. doi: 10.1016/0092-8674(95)90071-3.
Pubmed: 7538907
Rochat-Steiner V, Becker K, Micheau O, Schneider P, Burns K, Tschopp J: FIST/HIPK3: a Fas/FADD-interacting serine/threonine kinase that induces FADD phosphorylation and inhibits fas-mediated Jun NH(2)-terminal kinase activation. J Exp Med. 2000 Oct 16;192(8):1165-74. doi: 10.1084/jem.192.8.1165.
Pubmed: 11034606
Bolze A, Byun M, McDonald D, Morgan NV, Abhyankar A, Premkumar L, Puel A, Bacon CM, Rieux-Laucat F, Pang K, Britland A, Abel L, Cant A, Maher ER, Riedl SJ, Hambleton S, Casanova JL: Whole-exome-sequencing-based discovery of human FADD deficiency. Am J Hum Genet. 2010 Dec 10;87(6):873-81. doi: 10.1016/j.ajhg.2010.10.028. Epub 2010 Nov 25.
Pubmed: 21109225
Wang J, Chun HJ, Wong W, Spencer DM, Lenardo MJ: Caspase-10 is an initiator caspase in death receptor signaling. Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13884-8. doi: 10.1073/pnas.241358198.
Pubmed: 11717445
Kim MS, Oh JE, Min CK, Lee S, Chung NG, Yoo NJ, Lee SH: Mutational analysis of CASP10 gene in acute leukaemias and multiple myelomas. Pathology. 2009;41(5):484-7.
Pubmed: 19900088
Oh JE, Kim MS, Ahn CH, Kim SS, Han JY, Lee SH, Yoo NJ: Mutational analysis of CASP10 gene in colon, breast, lung and hepatocellular carcinomas. Pathology. 2010 Jan;42(1):73-6. doi: 10.3109/00313020903434371.
Pubmed: 20025484
Yang X, Khosravi-Far R, Chang HY, Baltimore D: Daxx, a novel Fas-binding protein that activates JNK and apoptosis. Cell. 1997 Jun 27;89(7):1067-76. doi: 10.1016/s0092-8674(00)80294-9.
Pubmed: 9215629
Kiriakidou M, Driscoll DA, Lopez-Guisa JM, Strauss JF 3rd: Cloning and expression of primate Daxx cDNAs and mapping of the human gene to chromosome 6p21.3 in the MHC region. DNA Cell Biol. 1997 Nov;16(11):1289-98. doi: 10.1089/dna.1997.16.1289.
Pubmed: 9407001
Pluta AF, Earnshaw WC, Goldberg IG: Interphase-specific association of intrinsic centromere protein CENP-C with HDaxx, a death domain-binding protein implicated in Fas-mediated cell death. J Cell Sci. 1998 Jul 30;111 ( Pt 14):2029-41.
Pubmed: 9645950
Shu HB, Halpin DR, Goeddel DV: Casper is a FADD- and caspase-related inducer of apoptosis. Immunity. 1997 Jun;6(6):751-63.
Pubmed: 9208847
Han DK, Chaudhary PM, Wright ME, Friedman C, Trask BJ, Riedel RT, Baskin DG, Schwartz SM, Hood L: MRIT, a novel death-effector domain-containing protein, interacts with caspases and BclXL and initiates cell death. Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11333-8. doi: 10.1073/pnas.94.21.11333.
Pubmed: 9326610
Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, Steiner V, Bodmer JL, Schroter M, Burns K, Mattmann C, Rimoldi D, French LE, Tschopp J: Inhibition of death receptor signals by cellular FLIP. Nature. 1997 Jul 10;388(6638):190-5. doi: 10.1038/40657.
Pubmed: 9217161
Inohara N, del Peso L, Koseki T, Chen S, Nunez G: RICK, a novel protein kinase containing a caspase recruitment domain, interacts with CLARP and regulates CD95-mediated apoptosis. J Biol Chem. 1998 May 15;273(20):12296-300. doi: 10.1074/jbc.273.20.12296.
Pubmed: 9575181
McCarthy JV, Ni J, Dixit VM: RIP2 is a novel NF-kappaB-activating and cell death-inducing kinase. J Biol Chem. 1998 Jul 3;273(27):16968-75. doi: 10.1074/jbc.273.27.16968.
Pubmed: 9642260
Thome M, Hofmann K, Burns K, Martinon F, Bodmer JL, Mattmann C, Tschopp J: Identification of CARDIAK, a RIP-like kinase that associates with caspase-1. Curr Biol. 1998 Jul 16;8(15):885-8. doi: 10.1016/s0960-9822(07)00352-1.
Pubmed: 9705938
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