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Gene Review

Fasl  -  Fas ligand (TNF superfamily, member 6)

Mus musculus

Synonyms: APT1LG1, Apt1lg1, CD178, CD95 ligand, CD95-L, ...
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Disease relevance of Fasl


Psychiatry related information on Fasl


High impact information on Fasl

  • The autosomal recessive lpr and gld genes induce in mice multiple autoantibodies and the progressive accumulation of large numbers of non-malignant CD4- CD8- T lymphocytes [11].
  • Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease [11].
  • The gld gene is located on chromosome 1; its product is also unknown [11].
  • Foreign antigens that stimulate the BCR acutely cause CD40L and FasL to promote clonal proliferation [12].
  • Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand [3].

Chemical compound and disease context of Fasl


Biological context of Fasl


Anatomical context of Fasl


Associations of Fasl with chemical compounds


Physical interactions of Fasl


Regulatory relationships of Fasl


Other interactions of Fasl

  • Thymuses from nur77/N10-transgenic mice on a gld/gld background have increased cellularity and an almost normal profile of thymocyte subpopulations [36].
  • These findings illustrate that RNS cause cell death in a Fas- and JNK-dependent manner and that this occurs through a pathway distinct from FasL [37].
  • Our results show that primary mixed lymphocyte reaction (MLR)-derived CTLs from granzyme B-/- x gld/gld mice induce apoptosis of allogeneic targets with less efficiency and a longer delay than CTLs deficient for granzyme B alone [38].
  • In these models, T cell-mediated tumor regression and long-term antitumor immunity are perforin and FasL independent [39].
  • In addition, macrophages either deficient in FasL or lacking p53 showed resistance to the effect of morphine [40].
  • Hematopoietic stem and progenitor cells are insensitive to Fas-mediated apoptosis and thus can exploit the constitutive expression of FasL to exert potent veto activities in the early stages of engraftment [41].

Analytical, diagnostic and therapeutic context of Fasl


  1. Evidence for selective transformation of autoreactive immature plasma cells in mice deficient in Fasl. Zhang, J.Q., Okumura, C., McCarty, T., Shin, M.S., Mukhopadhyay, P., Hori, M., Torrey, T.A., Naghashfar, Z., Zhou, J.X., Lee, C.H., Roopenian, D.C., Morse, H.C., Davidson, W.F. J. Exp. Med. (2004) [Pubmed]
  2. Par-4 drives trafficking and activation of Fas and Fasl to induce prostate cancer cell apoptosis and tumor regression. Chakraborty, M., Qiu, S.G., Vasudevan, K.M., Rangnekar, V.M. Cancer Res. (2001) [Pubmed]
  3. Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Takahashi, T., Tanaka, M., Brannan, C.I., Jenkins, N.A., Copeland, N.G., Suda, T., Nagata, S. Cell (1994) [Pubmed]
  4. Fas ligand (CD95 ligand) controls angiogenesis beneath the retina. Kaplan, H.J., Leibole, M.A., Tezel, T., Ferguson, T.A. Nat. Med. (1999) [Pubmed]
  5. Caspase-1-independent, Fas/Fas ligand-mediated IL-18 secretion from macrophages causes acute liver injury in mice. Tsutsui, H., Kayagaki, N., Kuida, K., Nakano, H., Hayashi, N., Takeda, K., Matsui, K., Kashiwamura, S., Hada, T., Akira, S., Yagita, H., Okamura, H., Nakanishi, K. Immunity (1999) [Pubmed]
  6. Fas ligand-dependent inflammatory regulation in acute myocarditis induced by Trypanosoma cruzi infection. de Oliveira, G.M., Diniz, R.L., Batista, W., Batista, M.M., Bani Correa, C., de Araújo-Jorge, T.C., Henriques-Pons, A. Am. J. Pathol. (2007) [Pubmed]
  7. CD8+ T cells promote inflammation and apoptosis in the liver after sepsis: role of Fas-FasL. Wesche-Soldato, D.E., Chung, C.S., Gregory, S.H., Salazar-Mather, T.P., Ayala, C.A., Ayala, A. Am. J. Pathol. (2007) [Pubmed]
  8. Protection from autoimmune diabetes and T-cell lymphoproliferation induced by FasL mutation are differentially regulated and can be uncoupled pharmacologically. Mohamood, A.S., Guler, M.L., Xiao, Z., Zheng, D., Hess, A., Wang, Y., Yagita, H., Schneck, J.P., Hamad, A.R. Am. J. Pathol. (2007) [Pubmed]
  9. Loss of functional Fas ligand enhances intestinal tumorigenesis in the Min mouse model. Fingleton, B., Carter, K.J., Matrisian, L.M. Cancer Res. (2007) [Pubmed]
  10. Antitumor activity induced by regulatory RNA: possible role of RNA-dependent protein kinase and nuclear factor-kappaB. Watanabe, M.A., Rodrigues Souza, L., Murad, J.M., De Lucca, F.L. Eur. J. Pharmacol. (2003) [Pubmed]
  11. Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease. Cohen, P.L., Eisenberg, R.A. Annu. Rev. Immunol. (1991) [Pubmed]
  12. Expansion or elimination of B cells in vivo: dual roles for CD40- and Fas (CD95)-ligands modulated by the B cell antigen receptor. Rathmell, J.C., Townsend, S.E., Xu, J.C., Flavell, R.A., Goodnow, C.C. Cell (1996) [Pubmed]
  13. The mycotoxin penicillic acid inhibits Fas ligand-induced apoptosis by blocking self-processing of caspase-8 in death-inducing signaling complex. Bando, M., Hasegawa, M., Tsuboi, Y., Miyake, Y., Shiina, M., Ito, M., Handa, H., Nagai, K., Kataoka, T. J. Biol. Chem. (2003) [Pubmed]
  14. The Fas/Fas-ligand system is not required for bleomycin-induced pulmonary fibrosis in mice. Aoshiba, K., Yasui, S., Tamaoki, J., Nagai, A. Am. J. Respir. Crit. Care Med. (2000) [Pubmed]
  15. Impaired clearance of apoptotic cells promotes synergy between atherogenesis and autoimmune disease. Aprahamian, T., Rifkin, I., Bonegio, R., Hugel, B., Freyssinet, J.M., Sato, K., Castellot, J.J., Walsh, K. J. Exp. Med. (2004) [Pubmed]
  16. Crm-A, bcl-2 and NDGA inhibit CD95L-induced apoptosis of malignant glioma cells at the level of caspase 8 processing. Wagenknecht, B., Schulz, J.B., Gulbins, E., Weller, M. Cell Death Differ. (1998) [Pubmed]
  17. IL-18-binding protein protects against lipopolysaccharide- induced lethality and prevents the development of Fas/Fas ligand-mediated models of liver disease in mice. Faggioni, R., Cattley, R.C., Guo, J., Flores, S., Brown, H., Qi, M., Yin, S., Hill, D., Scully, S., Chen, C., Brankow, D., Lewis, J., Baikalov, C., Yamane, H., Meng, T., Martin, F., Hu, S., Boone, T., Senaldi, G. J. Immunol. (2001) [Pubmed]
  18. Comparison of Fas(Apo-1/CD95)- and perforin-mediated cytotoxicity in primary T lymphocytes. Lowin, B., Mattman, C., Hahne, M., Tschopp, J. Int. Immunol. (1996) [Pubmed]
  19. The mouse Fas-ligand gene is mutated in gld mice and is part of a TNF family gene cluster. Lynch, D.H., Watson, M.L., Alderson, M.R., Baum, P.R., Miller, R.E., Tough, T., Gibson, M., Davis-Smith, T., Smith, C.A., Hunter, K. Immunity (1994) [Pubmed]
  20. Massive upregulation of the Fas ligand in lpr and gld mice: implications for Fas regulation and the graft-versus-host disease-like wasting syndrome. Chu, J.L., Ramos, P., Rosendorff, A., Nikolić-Zugić, J., Lacy, E., Matsuzawa, A., Elkon, K.B. J. Exp. Med. (1995) [Pubmed]
  21. Sertoli cells induce xenolymphocyte apoptosis in vitro. Yin, Z.Z., Xie, L., Zeng, M.H., Li, R., Huang, Y.B., Zhu, M., Chen, G., Chen, S. Transplant. Proc. (2006) [Pubmed]
  22. Dual role for Fas ligand in the initiation of and recovery from experimental allergic encephalomyelitis. Sabelko-Downes, K.A., Cross, A.H., Russell, J.H. J. Exp. Med. (1999) [Pubmed]
  23. Regulation of fas ligand expression during activation-induced cell death in T cells by p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase. Zhang, J., Gao, J.X., Salojin, K., Shao, Q., Grattan, M., Meagher, C., Laird, D.W., Delovitch, T.L. J. Exp. Med. (2000) [Pubmed]
  24. 9-cis retinoic acid inhibition of activation-induced apoptosis is mediated via regulation of fas ligand and requires retinoic acid receptor and retinoid X receptor activation. Bissonnette, R.P., Brunner, T., Lazarchik, S.B., Yoo, N.J., Boehm, M.F., Green, D.R., Heyman, R.A. Mol. Cell. Biol. (1995) [Pubmed]
  25. Ceramide-induced cell death is independent of the Fas/Fas ligand pathway and is prevented by Nur77 overexpression in A20 B cells. Brás, A., Albar, J.P., Leonardo, E., de Buitrago, G.G., Martínez-A, C. Cell Death Differ. (2000) [Pubmed]
  26. The chemotherapeutic drug 5-fluorouracil induces apoptosis in mouse thymocytes in vivo via activation of the CD95(APO-1/Fas) system. Eichhorst, S.T., Müerköster, S., Weigand, M.A., Krammer, P.H. Cancer Res. (2001) [Pubmed]
  27. Oocyte attrition. Reynaud, K., Driancourt, M.A. Mol. Cell. Endocrinol. (2000) [Pubmed]
  28. Inhibitory function of two NFAT family members in lymphoid homeostasis and Th2 development. Ranger, A.M., Oukka, M., Rengarajan, J., Glimcher, L.H. Immunity (1998) [Pubmed]
  29. Involvement of donor T-cell cytotoxic effector mechanisms in preventing allogeneic marrow graft rejection. Martin, P.J., Akatsuka, Y., Hahne, M., Sale, G. Blood (1998) [Pubmed]
  30. Intratumoral delivery of dendritic cells engineered to secrete both interleukin (IL)-12 and IL-18 effectively treats local and distant disease in association with broadly reactive Tc1-type immunity. Tatsumi, T., Huang, J., Gooding, W.E., Gambotto, A., Robbins, P.D., Vujanovic, N.L., Alber, S.M., Watkins, S.C., Okada, H., Storkus, W.J. Cancer Res. (2003) [Pubmed]
  31. Pathogen-associated molecular patterns sensitize macrophages to Fas ligand-induced apoptosis and IL-1 beta release. Fukui, M., Imamura, R., Umemura, M., Kawabe, T., Suda, T. J. Immunol. (2003) [Pubmed]
  32. Perforin and Fas act together in the induction of apoptosis, and both are critical in the clearance of lymphocytic choriomeningitis virus infection. Rode, M., Balkow, S., Sobek, V., Brehm, R., Martin, P., Kersten, A., Dumrese, T., Stehle, T., Müllbacher, A., Wallich, R., Simon, M.M. J. Virol. (2004) [Pubmed]
  33. Defined inflammatory states in astrocyte cultures: correlation with susceptibility towards CD95-driven apoptosis. Falsig, J., Latta, M., Leist, M. J. Neurochem. (2004) [Pubmed]
  34. Regulation of Fas (CD95)-induced apoptosis by nuclear factor-kappaB and tumor necrosis factor-alpha in macrophages. Lu, B., Wang, L., Medan, D., Toledo, D., Huang, C., Chen, F., Shi, X., Rojanasakul, Y. Am. J. Physiol., Cell Physiol. (2002) [Pubmed]
  35. Stimulation of microglial metabotropic glutamate receptor mGlu2 triggers tumor necrosis factor alpha-induced neurotoxicity in concert with microglial-derived Fas ligand. Taylor, D.L., Jones, F., Kubota, E.S., Pocock, J.M. J. Neurosci. (2005) [Pubmed]
  36. Apoptosis of nur77/N10-transgenic thymocytes involves the Fas/Fas ligand pathway. Weih, F., Ryseck, R.P., Chen, L., Bravo, R. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  37. Reactive nitrogen species-induced cell death requires Fas-dependent activation of c-Jun N-terminal kinase. Shrivastava, P., Pantano, C., Watkin, R., McElhinney, B., Guala, A., Poynter, M.L., Persinger, R.L., Budd, R., Janssen-Heininger, Y. Mol. Cell. Biol. (2004) [Pubmed]
  38. Mechanisms responsible for granzyme B-independent cytotoxicity. Shresta, S., Russell, J.H., Ley, T.J. Blood (1997) [Pubmed]
  39. Tumor regression after adoptive transfer of effector T cells is independent of perforin or Fas ligand (APO-1L/CD95L). Winter, H., Hu, H.M., Urba, W.J., Fox, B.A. J. Immunol. (1999) [Pubmed]
  40. Role of p38 mitogen-activated protein kinase phosphorylation and Fas-Fas ligand interaction in morphine-induced macrophage apoptosis. Singhal, P.C., Bhaskaran, M., Patel, J., Patel, K., Kasinath, B.S., Duraisamy, S., Franki, N., Reddy, K., Kapasi, A.A. J. Immunol. (2002) [Pubmed]
  41. Fas ligand enhances hematopoietic cell engraftment through abrogation of alloimmune responses and nonimmunogenic interactions. Pearl-Yafe, M., Yolcu, E.S., Stein, J., Kaplan, O., Yaniv, I., Shirwan, H., Askenasy, N. Stem. Cells (2007) [Pubmed]
  42. Radiation and stress-induced apoptosis: a role for Fas/Fas ligand interactions. Reap, E.A., Roof, K., Maynor, K., Borrero, M., Booker, J., Cohen, P.L. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  43. Therapeutic neutralization of CD95-ligand and TNF attenuates brain damage in stroke. Martin-Villalba, A., Hahne, M., Kleber, S., Vogel, J., Falk, W., Schenkel, J., Krammer, P.H. Cell Death Differ. (2001) [Pubmed]
  44. Fas ligand (CD95L) protects neurons against perforin-mediated T lymphocyte cytotoxicity. Medana, I., Li, Z., Flügel, A., Tschopp, J., Wekerle, H., Neumann, H. J. Immunol. (2001) [Pubmed]
  45. The Fas/Fas ligand pathway is important for optimal tumor regression in a mouse model of CTL adoptive immunotherapy of experimental CMS4 lung metastases. Caldwell, S.A., Ryan, M.H., McDuffie, E., Abrams, S.I. J. Immunol. (2003) [Pubmed]
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