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Gene Review

FASLG  -  Fas ligand (TNF superfamily, member 6)

Homo sapiens

Synonyms: ALPS1B, APT1LG1, APTL, Apoptosis antigen ligand, CD178, ...
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Disease relevance of FASLG

  • We hypothesize that increased levels of CCL2 in the endometriotic environment may upregulate FASLG expression in human endometrial stromal cells and induce a local immunotolerance in endometriosis [1].
  • Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer [2].
  • As CD4 molecules are the primary receptors for human immunodeficiency virus 1 (HIV-1), we conclude that HIV-1 envelope mediated CD4XL can lead to the generation of FasL-expressing CD4(+) T cells that can lead to apoptosis of CD4 as well as CD8 T cells [3].
  • HIV-1 Nef-induced FasL induction and bystander killing requires p38 MAPK activation [4].
  • Agonistic anti-Fas antibodies and multimeric recombinant Fas ligand (FasL) preparations show high tumoricidal activity against leukemic cells, but are unsuitable for clinical application due to unacceptable systemic toxicity [5].
  • Breast cancer patients with the FASL -844CC genotype had higher apoptotic TILs in their cancer tissues than those with the FASL -844TT genotype (33.7 +/- 1.2% versus 19.1 +/- 2.0%; P = 0.007) [6].

Psychiatry related information on FASLG


High impact information on FASLG

  • Active antigen-driven death is mediated by the expression of death cytokines such as FasL and TNF [12].
  • Within the nucleus, FKHRL1 triggers apoptosis most likely by inducing the expression of genes that are critical for cell death, such as the Fas ligand gene [13].
  • These encode amino acid substitutions that decrease caspase activity and interfere with death receptor-induced apoptosis, particularly that stimulated by Fas ligand and TRAIL [14].
  • Northern hybridization revealed that Fas ligand is expressed in activated splenocytes and thymocytes, consistent with its involvement in T cell-mediated cytotoxicity and in several nonlymphoid tissues, such as testis [15].
  • The amino acid sequence indicated that Fas ligand is a type II transmembrane protein that belongs to the TNF family [15].

Chemical compound and disease context of FASLG


Biological context of FASLG


Anatomical context of FASLG


Associations of FASLG with chemical compounds


Physical interactions of FASLG


Enzymatic interactions of FASLG


Regulatory relationships of FASLG


Other interactions of FASLG


Analytical, diagnostic and therapeutic context of FASLG


  1. Regulation of FAS ligand expression by chemokine ligand 2 in human endometrial cells. Selam, B., Kayisli, U.A., Akbas, G.E., Basar, M., Arici, A. Biol. Reprod. (2006) [Pubmed]
  2. Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Pitti, R.M., Marsters, S.A., Lawrence, D.A., Roy, M., Kischkel, F.C., Dowd, P., Huang, A., Donahue, C.J., Sherwood, S.W., Baldwin, D.T., Godowski, P.J., Wood, W.I., Gurney, A.L., Hillan, K.J., Cohen, R.L., Goddard, A.D., Botstein, D., Ashkenazi, A. Nature (1998) [Pubmed]
  3. CD4 T lymphocytes are primed to express Fas ligand by CD4 cross-linking and to contribute to CD8 T-cell apoptosis via Fas/FasL death signaling pathway. Tateyama, M., Oyaizu, N., McCloskey, T.W., Than, S., Pahwa, S. Blood (2000) [Pubmed]
  4. HIV-1 Nef-induced FasL induction and bystander killing requires p38 MAPK activation. Muthumani, K., Choo, A.Y., Hwang, D.S., Premkumar, A., Dayes, N.S., Harris, C., Green, D.R., Wadsworth, S.A., Siekierka, J.J., Weiner, D.B. Blood (2005) [Pubmed]
  5. CD7-restricted activation of Fas-mediated apoptosis: a novel therapeutic approach for acute T-cell leukemia. Bremer, E., ten Cate, B., Samplonius, D.F., de Leij, L.F., Helfrich, W. Blood (2006) [Pubmed]
  6. Functional polymorphisms in FAS and FASL contribute to increased apoptosis of tumor infiltration lymphocytes and risk of breast cancer. Zhang, B., Sun, T., Xue, L., Han, X., Zhang, B., Lu, N., Shi, Y., Tan, W., Zhou, Y., Zhao, D., Zhang, X., Guo, Y., Lin, D. Carcinogenesis (2007) [Pubmed]
  7. Comparison of circulating proinflammatory cytokines and soluble apoptosis mediators in patients with chronic heart failure with versus without symptoms of depression. Parissis, J.T., Adamopoulos, S., Rigas, A., Kostakis, G., Karatzas, D., Venetsanou, K., Kremastinos, D.T. Am. J. Cardiol. (2004) [Pubmed]
  8. Induction of tumour cell apoptosis by matrix metalloproteinase inhibitors: new tricks from a (not so) old drug. Mitsiades, N., Poulaki, V., Mitsiades, C.S., Anderson, K.C. Expert opinion on investigational drugs. (2001) [Pubmed]
  9. Metalloproteinase shedding of Fas ligand regulates beta-amyloid neurotoxicity. Ethell, D.W., Kinloch, R., Green, D.R. Curr. Biol. (2002) [Pubmed]
  10. On the role and significance of Fas (Apo-1/CD95) ligand (FasL) expression in immune privileged tissues and cancer cells using multiple myeloma as a model. Greil, R., Egle, A., Villunger, A. Leuk. Lymphoma (1998) [Pubmed]
  11. Elevated levels of soluble Fas and Fas ligand in cerebrospinal fluid of patients with AIDS dementia complex. Sabri, F., De Milito, A., Pirskanen, R., Elovaara, I., Hagberg, L., Cinque, P., Price, R., Chiodi, F. J. Neuroimmunol. (2001) [Pubmed]
  12. Mature T lymphocyte apoptosis--immune regulation in a dynamic and unpredictable antigenic environment. Lenardo, M., Chan, K.M., Hornung, F., McFarland, H., Siegel, R., Wang, J., Zheng, L. Annu. Rev. Immunol. (1999) [Pubmed]
  13. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Brunet, A., Bonni, A., Zigmond, M.J., Lin, M.Z., Juo, P., Hu, L.S., Anderson, M.J., Arden, K.C., Blenis, J., Greenberg, M.E. Cell (1999) [Pubmed]
  14. Inherited human Caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type II. Wang, J., Zheng, L., Lobito, A., Chan, F.K., Dale, J., Sneller, M., Yao, X., Puck, J.M., Straus, S.E., Lenardo, M.J. Cell (1999) [Pubmed]
  15. Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Suda, T., Takahashi, T., Golstein, P., Nagata, S. Cell (1993) [Pubmed]
  16. NF-kappaB-independent actions of sulfasalazine dissociate the CD95L- and Apo2L/TRAIL-dependent death signaling pathways in human malignant glioma cells. Hermisson, M., Weller, M. Cell Death Differ. (2003) [Pubmed]
  17. Induction of Fas expression and augmentation of Fas/Fas ligand-mediated apoptosis by the synthetic retinoid CD437 in human lung cancer cells. Sun, S.Y., Yue, P., Hong, W.K., Lotan, R. Cancer Res. (2000) [Pubmed]
  18. Sustained activation of JNK/p38 MAPK pathways in response to cisplatin leads to Fas ligand induction and cell death in ovarian carcinoma cells. Mansouri, A., Ridgway, L.D., Korapati, A.L., Zhang, Q., Tian, L., Wang, Y., Siddik, Z.H., Mills, G.B., Claret, F.X. J. Biol. Chem. (2003) [Pubmed]
  19. FAS/FAS ligand ratio: a marker of oxaliplatin-based intrinsic and acquired resistance in advanced colorectal cancer. Nadal, C., Maurel, J., Gallego, R., Castells, A., Longarón, R., Marmol, M., Sanz, S., Molina, R., Martin-Richard, M., Gascón, P. Clin. Cancer Res. (2005) [Pubmed]
  20. DNA damaging agents induce expression of Fas ligand and subsequent apoptosis in T lymphocytes via the activation of NF-kappa B and AP-1. Kasibhatla, S., Brunner, T., Genestier, L., Echeverri, F., Mahboubi, A., Green, D.R. Mol. Cell (1998) [Pubmed]
  21. 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]
  22. Estrogen protects bone by inducing Fas ligand in osteoblasts to regulate osteoclast survival. Krum, S.A., Miranda-Carboni, G.A., Hauschka, P.V., Carroll, J.S., Lane, T.F., Freedman, L.P., Brown, M. EMBO. J. (2008) [Pubmed]
  23. Identification of amino acid residues important for ligand binding to Fas. Starling, G.C., Bajorath, J., Emswiler, J., Ledbetter, J.A., Aruffo, A., Kiener, P.A. J. Exp. Med. (1997) [Pubmed]
  24. Ultraviolet light induces apoptosis via direct activation of CD95 (Fas/APO-1) independently of its ligand CD95L. Aragane, Y., Kulms, D., Metze, D., Wilkes, G., Pöppelmann, B., Luger, T.A., Schwarz, T. J. Cell Biol. (1998) [Pubmed]
  25. Activation of CD95 (APO-1/Fas) signaling by ceramide mediates cancer therapy-induced apoptosis. Herr, I., Wilhelm, D., Böhler, T., Angel, P., Debatin, K.M. EMBO J. (1997) [Pubmed]
  26. Activation-dependent transcriptional regulation of the human Fas promoter requires NF-kappaB p50-p65 recruitment. Chan, H., Bartos, D.P., Owen-Schaub, L.B. Mol. Cell. Biol. (1999) [Pubmed]
  27. Casper is a FADD- and caspase-related inducer of apoptosis. Shu, H.B., Halpin, D.R., Goeddel, D.V. Immunity (1997) [Pubmed]
  28. Cyclosporin A-sensitive transcription factor Egr-3 regulates Fas ligand expression. Mittelstadt, P.R., Ashwell, J.D. Mol. Cell. Biol. (1998) [Pubmed]
  29. c-Jun-dependent CD95-L expression is a rate-limiting step in the induction of apoptosis by alkylating agents. Kolbus, A., Herr, I., Schreiber, M., Debatin, K.M., Wagner, E.F., Angel, P. Mol. Cell. Biol. (2000) [Pubmed]
  30. Fluorescence resonance energy transfer analysis of proapoptotic CD95-EGF receptor interactions in Huh7 cells. Eberle, A., Reinehr, R., Becker, S., Häussinger, D. Hepatology (2005) [Pubmed]
  31. Extracellular matrix interacts with soluble CD95L: retention and enhancement of cytotoxicity. Aoki, K., Kurooka, M., Chen, J.J., Petryniak, J., Nabel, E.G., Nabel, G.J. Nat. Immunol. (2001) [Pubmed]
  32. Stromelysin-1 (MMP-3) in synovial fluid of patients with rheumatoid arthritis has potential to cleave membrane bound Fas ligand. Matsuno, H., Yudoh, K., Watanabe, Y., Nakazawa, F., Aono, H., Kimura, T. J. Rheumatol. (2001) [Pubmed]
  33. Irradiation-induced up-regulation of Fas in esophageal squamous cell carcinoma is not accompanied by Fas ligand-mediated apoptosis. Rigberg, D.A., Centeno, J., Kim, F.S., Ke, B., Swenson, K., Maggard, M., McFadden, D.W. Journal of surgical oncology. (1999) [Pubmed]
  34. Serum concentration of soluble decoy receptor 3 in glioma patients before and after surgery. Hwang, S.L., Lin, C.L., Cheng, C.Y., Lin, F.A., Lieu, A.S., Howng, S.L., Lee, K.S. The Kaohsiung journal of medical sciences. (2004) [Pubmed]
  35. alpha-fetoprotein causes apoptosis in tumor cells via a pathway independent of CD95, TNFR1 and TNFR2 through activation of caspase-3-like proteases. Dudich, E., Semenkova, L., Dudich, I., Gorbatova, E., Tochtamisheva, N., Tatulov, E., Nikolaeva, M., Sukhikh, G. Eur. J. Biochem. (1999) [Pubmed]
  36. Matrix metalloproteinase-7-mediated cleavage of Fas ligand protects tumor cells from chemotherapeutic drug cytotoxicity. Mitsiades, N., Yu, W.H., Poulaki, V., Tsokos, M., Stamenkovic, I. Cancer Res. (2001) [Pubmed]
  37. Caspase-induced inactivation of the anti-apoptotic TRAF1 during Fas ligand-mediated apoptosis. Irmler, M., Steiner, V., Ruegg, C., Wajant, H., Tschopp, J. FEBS Lett. (2000) [Pubmed]
  38. Fas-ligand (CD178) and TRAIL synergistically induce apoptosis of CD40-activated chronic lymphocytic leukemia B cells. Dicker, F., Kater, A.P., Fukuda, T., Kipps, T.J. Blood (2005) [Pubmed]
  39. Stress-induced Fas ligand expression in T cells is mediated through a MEK kinase 1-regulated response element in the Fas ligand promoter. Faris, M., Latinis, K.M., Kempiak, S.J., Koretzky, G.A., Nel, A. Mol. Cell. Biol. (1998) [Pubmed]
  40. Hepatocytes as cytotoxic effector cells can induce cell death by CD95 ligand-mediated pathway. Guy, C.S., Wang, J., Michalak, T.I. Hepatology (2006) [Pubmed]
  41. Nonoxynol-9 induces apoptosis of endometrial explants by both caspase-dependent and -independent apoptotic pathways. Jain, J.K., Li, A., Nucatola, D.L., Minoo, P., Felix, J.C. Biol. Reprod. (2005) [Pubmed]
  42. Effect of a vascular endothelial growth factor (VEGF) inhibitory treatment on the folliculogenesis and ovarian apoptosis in gonadotropin-treated prepubertal rats. Abramovich, D., Parborell, F., Tesone, M. Biol. Reprod. (2006) [Pubmed]
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