fas ligand protein


Summary: A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.

Top Publications

  1. Griffith T, Brunner T, Fletcher S, Green D, Ferguson T. Fas ligand-induced apoptosis as a mechanism of immune privilege. Science. 1995;270:1189-92 pubmed
    ..FasL messenger RNA and protein were detectable in the eye. Thus, Fas-FasL interactions appear to be an important mechanism for the maintenance of immune privilege. ..
  2. O CONNELL J, O Sullivan G, Collins J, Shanahan F. The Fas counterattack: Fas-mediated T cell killing by colon cancer cells expressing Fas ligand. J Exp Med. 1996;184:1075-82 pubmed
  3. Bennett M, O CONNELL J, O Sullivan G, Brady C, Roche D, Collins J, et al. The Fas counterattack in vivo: apoptotic depletion of tumor-infiltrating lymphocytes associated with Fas ligand expression by human esophageal carcinoma. J Immunol. 1998;160:5669-75 pubmed
  4. Lee E, Hurh S, Cho B, Oh K, Kim S, Surh C, et al. CD70-CD27 ligation between neural stem cells and CD4+ T cells induces Fas-FasL-mediated T-cell death. Stem Cell Res Ther. 2013;4:56 pubmed publisher
    ..First, CD70 constitutively expressed on NSCs engaged CD27 on CD4(+) T cells, which induced Fas ligand expression on CD4(+) T cells. Second, CD4(+) T-cell apoptosis was followed by Fas-Fas ligand interaction in the CD4(+) T cells. ..
  5. Pezzella F, Harris A. When cancer co-opts the vasculature. N Engl J Med. 2014;370:2146-7 pubmed publisher
  6. Klebanoff C, Scott C, Leonardi A, Yamamoto T, Cruz A, Ouyang C, et al. Memory T cell-driven differentiation of naive cells impairs adoptive immunotherapy. J Clin Invest. 2016;126:318-34 pubmed publisher
  7. Chien M, Chang W, Lee W, Chang Y, Lai T, Chan D, et al. A Fas Ligand (FasL)-Fused Humanized Antibody Against Tumor-Associated Glycoprotein 72 Selectively Exhibits the Cytotoxic Effect Against Oral Cancer Cells with a Low FasL/Fas Ratio. Mol Cancer Ther. 2017;16:1102-1113 pubmed publisher
    ..Collectively, our data indicate that a tumor-targeting antibody fused to the FasL can be a powerful tool for OSCC treatment, especially in populations with a low FasL/Fas ratio. Mol Cancer Ther; 16(6); 1102-13. ©2017 AACR. ..
  8. Raats D, Frenkel N, van Schelven S, Rinkes I, Laoukili J, Kranenburg O. CD95 ligand induces senescence in mismatch repair-deficient human colon cancer via chronic caspase-mediated induction of DNA damage. Cell Death Dis. 2017;8:e2669 pubmed publisher
    ..We conclude that induction of senescence is a hitherto unrecognized consequence of high CD95 expression, which appears to be most relevant for CMS1. ..
  9. O CONNELL J, Bennett M, O Sullivan G, Collins J, Shanahan F. Fas counter-attack--the best form of tumor defense?. Nat Med. 1999;5:267-8 pubmed

More Information


  1. Sata M, Perlman H, Muruve D, Silver M, Ikebe M, Libermann T, et al. Fas ligand gene transfer to the vessel wall inhibits neointima formation and overrides the adenovirus-mediated T cell response. Proc Natl Acad Sci U S A. 1998;95:1213-7 pubmed
    ..These data demonstrate that Fas ligand gene transfer can effectively inhibit injury-induced vessel lesion formation and can allow adenovirus-harboring cells to evade immune destruction. ..
  2. Qiu M, Chen Y, Chen L, Zeng J, Liu J. Transforming growth factor ?1 and Fas ligand synergistically enhance immune tolerance in dendritic cells in liver transplantation. J Surg Res. 2017;218:180-193 pubmed publisher
    ..In this study, using a rat model of liver transplantation, we determined whether cotransfection of transforming growth factor ?1 (TGF-?1) and Fas ligand (FasL) in imDCs synergistically enhances immune tolerance...
  3. Nabhani S, Schipp C, Miskin H, Levin C, Postovsky S, Dujovny T, et al. STAT3 gain-of-function mutations associated with autoimmune lymphoproliferative syndrome like disease deregulate lymphocyte apoptosis and can be targeted by BH3 mimetic compounds. Clin Immunol. 2017;181:32-42 pubmed publisher
    ..Importantly, STAT3-mutant cells were more sensitive to death induced by the BCL2-inhibitor ABT-737 indicating a dependence on anti-apoptotic BCL2 proteins and potential novel therapeutic options. ..
  4. Ozel E, Duran G, Celik M, Duran N, Gunesacar R. Fas and Fas ligand gene polymorphisms in Turkish patients with Familial Mediterranean Fever. Gene. 2017;623:29-32 pubmed publisher
    ..844CC genotype in FMF patients may be related to delayed apoptosis of neutrophils and ultimately cause neutrophilic inflammation by increasing FASLG expression. ..
  5. Yoong K, Afford S, Randhawa S, Hubscher S, Adams D. Fas/Fas ligand interaction in human colorectal hepatic metastases: A mechanism of hepatocyte destruction to facilitate local tumor invasion. Am J Pathol. 1999;154:693-703 pubmed
  6. Bennett M, MacDonald K, Chan S, Luzio J, Simari R, Weissberg P. Cell surface trafficking of Fas: a rapid mechanism of p53-mediated apoptosis. Science. 1998;282:290-3 pubmed
    ..In contrast, lpr and gld fibroblasts were resistant to p53-induced apoptosis. Thus, p53 can mediate apoptosis through Fas transport from cytoplasmic stores. ..
  7. Luo J, Wang Y, Yu B, Qian H, He Y, Shi G. A Potential of sFasL in Preventing Gland Injury in Sjogren's Syndrome. Biomed Res Int. 2017;2017:5981432 pubmed publisher
    ..Furthermore, we here also observed that the protective cytokine IL-10 expression was positively correlated with sFasL expression. Thus, our results here suggest a potential of sFasL in maintaining gland organ homeostasis. ..
  8. Mariani S, Krammer P. Differential regulation of TRAIL and CD95 ligand in transformed cells of the T and B lymphocyte lineage. Eur J Immunol. 1998;28:973-82 pubmed
    ..Thus, even though TRAIL and CD95L share structural and functional properties, they have unique properties as they differ in their regulatory pathways, i.e. cell-type-dependent expression and sensitivity to protease inhibitors. ..
  9. Bustamante A, López Cancio E, Pich S, Penalba A, Giralt D, García Berrocoso T, et al. Blood Biomarkers for the Early Diagnosis of Stroke: The Stroke-Chip Study. Stroke. 2017;48:2419-2425 pubmed publisher
    ..Additional discovery of new biomarkers and improvement on laboratory techniques seem necessary for achieving a molecular diagnosis of stroke. ..
  10. Restifo N. Not so Fas: Re-evaluating the mechanisms of immune privilege and tumor escape. Nat Med. 2000;6:493-5 pubmed
  11. Okada K, Komuta K, Hashimoto S, Matsuzaki S, Kanematsu T, Koji T. Frequency of apoptosis of tumor-infiltrating lymphocytes induced by fas counterattack in human colorectal carcinoma and its correlation with prognosis. Clin Cancer Res. 2000;6:3560-4 pubmed
    ..This tumor immune evasion induced by FasL may therefore affect the malignant potential of human colorectal carcinoma. ..
  12. Lee C, Zhou Y, Roy Choudhury K, Siamakpour Reihani S, Young K, Hoang P, et al. Subtype-Specific Radiation Response and Therapeutic Effect of FAS Death Receptor Modulation in Human Breast Cancer. Radiat Res. 2017;188:169-180 pubmed publisher
    ..FAS activation concurrent with radiation slows tumor growth in the radiation-resistant subtypes, but the effect was not significant. Alternative subtype-specific modulators of radiation response are under investigation. ..
  13. Schwaderer J, Gaiser A, Phan T, Delgado M, Brunner T. Liver receptor homolog-1 (NR5a2) regulates CD95/Fas ligand transcription and associated T-cell effector functions. Cell Death Dis. 2017;8:e2745 pubmed publisher
    ..In summary, these data show for the first time LRH-1 expression in T cells, its role in FASLG transcription and the potential of pharmacological inhibition of LRH-1 in the treatment of FasL-mediated immunopathologies. ..
  14. McMenamin P. Macrophages coming of age: their role in promoting CNV is modulated by FasL. Invest Ophthalmol Vis Sci. 2013;54:5332 pubmed publisher
  15. Poetschke H, Klug D, Walker D, Richie E. Cross-linking the TCR complex induces apoptosis in CD4+8+ thymocytes in the presence of cyclosporin A. Dev Immunol. 1996;5:1-15 pubmed
  16. Tohyama M, Shirakata Y, Sayama K, Hashimoto K. A marked increase in serum soluble Fas ligand in drug-induced hypersensitivity syndrome. Br J Dermatol. 2008;159:981-4 pubmed publisher
  17. Shiraki K, Tsuji N, Shioda T, Isselbacher K, Takahashi H. Expression of Fas ligand in liver metastases of human colonic adenocarcinomas. Proc Natl Acad Sci U S A. 1997;94:6420-5 pubmed
    ..Furthermore, constitutive expression of FasL in hepatic metastatic tumors suggests that FasL may also be important in their colonization in the liver through induction of apoptosis in the surrounding Fas-expressing hepatocytes. ..
  18. Kayagaki N, Yamaguchi N, Nakayama M, Kawasaki A, Akiba H, Okumura K, et al. Involvement of TNF-related apoptosis-inducing ligand in human CD4+ T cell-mediated cytotoxicity. J Immunol. 1999;162:2639-47 pubmed
    ..These results indicate a differential regulation of TRAIL and FasL expression on human CD4+ T cell clones and that TRAIL constitutes an additional pathway of T cell-mediated cytotoxicity. ..
  19. Le Negrate G, Selva E, Auberger P, Rossi B, Hofman P. Sustained polymorphonuclear leukocyte transmigration induces apoptosis in T84 intestinal epithelial cells. J Cell Biol. 2000;150:1479-88 pubmed
    ..This apoptotic process appears to involve remodeling of the actin cytoskeleton of enterocytes independent of the Fas/Fas ligand pathway. ..
  20. MUSCHEN M, Warskulat U, Peters Regehr T, Bode J, Kubitz R, Haussinger D. Involvement of CD95 (Apo-1/Fas) ligand expressed by rat Kupffer cells in hepatic immunoregulation. Gastroenterology. 1999;116:666-77 pubmed
  21. Chen J, Wang Y, Zhuo L, Liu Z, Liu T, Li W, et al. Fas signaling induces stemness properties in colorectal cancer by regulation of Bmi1. Mol Carcinog. 2017;56:2267-2278 pubmed publisher
  22. Wang K, Tao L, Su J, Zhang Y, Zou B, Wang Y, et al. TLR4 supports the expansion of FasL+CD5+CD1dhi regulatory B cells, which decreases in contact hypersensitivity. Mol Immunol. 2017;87:188-199 pubmed publisher
  23. Yin D, Tuthill D, Mufson R, Shi Y. Chronic restraint stress promotes lymphocyte apoptosis by modulating CD95 expression. J Exp Med. 2000;191:1423-8 pubmed
    ..Moreover, chronic physical restraint failed to induce a decrease in lymphocyte numbers in CD95-deficient (Fas(lpr/lpr)) mice. Therefore, stress modulates the immune system through CD95-mediated apoptosis dependent on endogenous opioids. ..
  24. Taylor M, de Boer Brouwer M, Woolveridge I, Teerds K, Morris I. Leydig cell apoptosis after the administration of ethane dimethanesulfonate to the adult male rat is a Fas-mediated process. Endocrinology. 1999;140:3797-804 pubmed
    ..We also investigated the role of the Fas system in Leydig cell apoptosis. Both Fas receptor and Fas ligand protein levels increased after EDS, peaking at 12-18 h and declining thereafter...
  25. Hohlbaum A, Moe S, Marshak Rothstein A. Opposing effects of transmembrane and soluble Fas ligand expression on inflammation and tumor cell survival. J Exp Med. 2000;191:1209-20 pubmed
    ..However, expression of soluble FasL was not benign, but actually suppressed the inflammatory response and protected other transfectants from the effector mechanisms elicted by membrane-bound FasL. ..
  26. Horn S, Hughes M, Schilling R, Sticht C, Tenev T, Ploesser M, et al. Caspase-10 Negatively Regulates Caspase-8-Mediated Cell Death, Switching the Response to CD95L in Favor of NF-κB Activation and Cell Survival. Cell Rep. 2017;19:785-797 pubmed publisher
    ..Thus, our data are consistent with a model in which both caspase-10 and cFLIP coordinately regulate CD95L-mediated signaling for death or survival. ..
  27. Ohshima K, Shimazaki K, Kume T, Suzumiya J, Kanda M, Kikuchi M. Perforin and Fas pathways of cytotoxic T-cells in histiocytic necrotizing lymphadenitis. Histopathology. 1998;33:471-8 pubmed
    ..As a result, both pathways seemed to induce an abundance of apoptosis and thus induce necrotizing lesions. ..
  28. Rogge M, Yin X, Godfrey L, Lakireddy P, Potter C, Del Rosso C, et al. Therapeutic Use of Soluble Fas Ligand Ameliorates Acute and Recurrent Herpetic Stromal Keratitis in Mice. Invest Ophthalmol Vis Sci. 2015;56:6377-86 pubmed publisher
  29. Zhang J, Gao J, Salojin K, Shao Q, Grattan M, Meagher C, et al. 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. J Exp Med. 2000;191:1017-30 pubmed
    ..Subsequently, caspases stimulate JNK to further upregulate FasL expression. Thus, p38 MAPK and downstream JNK converge to regulate FasL expression at different times after T cell receptor stimulation to elicit maximum AICD. ..
  30. Yu Y, Liao L, Shao B, Su X, Shuai Y, Wang H, et al. Knockdown of MicroRNA Let-7a Improves the Functionality of Bone Marrow-Derived Mesenchymal Stem Cells in Immunotherapy. Mol Ther. 2017;25:480-493 pubmed publisher
    ..With high safety and convenience, knockdown of let-7a is a potential strategy to improve MSC therapy for inflammatory diseases in clinic. ..
  31. Fischer B, Muller B, Fischer K, Baur N, Kreutz W. Acidic pH inhibits non-MHC-restricted killer cell functions. Clin Immunol. 2000;96:252-63 pubmed
    ..Thus, an acidic microenvironment within solid tumors may contribute to the observed immunosuppression in vivo, compromising antitumoral defense and immunotherapy in general, respectively. ..
  32. Jeremias I, Herr I, Boehler T, Debatin K. TRAIL/Apo-2-ligand-induced apoptosis in human T cells. Eur J Immunol. 1998;28:143-52 pubmed
    ..These data suggest that TRAIL might participate in CD95-independent apoptosis of lymphoid cells and might be involved in deregulated apoptosis in diseases such as leukemias and HIV-1 infection. ..