Type |
Details |
Score |
Protein Domain |
Type: |
Family |
Description: |
Like all apoptotic cell death, T cell receptor (TCR)-mediated death can bedivided into two phases: an inductive phase and an effector phase. The effector phase includes a sequence of steps that are common to apoptosis inmany cell types, which, if not interrupted, will lead to cell death. Theinduction phase, which often requires the expression of new genes, consistsof a set of signals that activate the effector phase. Outside the thymus,most, if not all, of the TCR-mediated apoptosis of mature T cells (sometimesreferred to as activation-induced cell death (AICD)) is induced through thesurface antigen Fas pathway: activation through the TCR induces expressionof the Fas (CD95) ligand (FasL); the expression of FasL on either aneighbouring cell, or on the Fas-bearing cell, induces trimerisation of Fas,which then initiates a signal-transduction cascade, leading to apoptosis of the Fas-bearing cell. This commitment stage requires the activation of keydeath-inducing enzymes, termed caspases, which act by cleaving proteins thatare essential for cell survival and proliferation[, ]. However whathappens to FasL itself remains unknown. It is possible that it is cleavedfrom the effector cells and internalised into the target cells; it may bedownregulated in the effector cells; or it may be phagocytosed by the targetcells.Fas is also known to be essential in the death of hyperactivated peripheralCD4 cells: in the absence of Fas, mature peripheral T cells do not die, butthe activated cells continue to proliferate, producing cytokines that leadto grossly enlarged lymph nodes and spleen. Defects in the Fas-FasL systemare associated with various disease syndromes. Mice with non-functional Fasor FasL display characteristics of lymphoproliferative disorder, such as lymphadenopathy, splenomegaly, and elevated secretion of IgM and IgG. Thesemice also secrete anti-DNA autoantibodies and rheumatoid factor [].FasL (also known as tumor necrosis factor ligand superfamily member 6) is a 40kDa type II membrane protein belonging to the tumour necrosisfactor (TNF) family. Its binding to the cognate Fas receptor triggers the apoptosis that plays a pivotal role in the maintenance of immune system homeostasis. It is expressed on activated lymphocytes, NK cells,platelets, certain immune-privileged cells and some tumour cells[, ]. The cell death-inducing property of FasL has been associated with its extracellular domain, which can be cleaved off by metalloprotease activity to produce soluble FasL [].Human and mouse FasL induce apoptosis in cells expressing either mouse orhuman Fas with the same specificity. Although the amino acid sequence ofFasL is highly conserved between human and mouse, the similarity betweenhuman and murine Fas is much less pronounced. Greater conservation of theligand than the receptor is also observed in other members of the TNF family.By comparison with other TNF family members, FasL has a long N-terminal intracellular region rich in proline residues, which is known tobind to the SH3 domain. SH3 domains play important roles in mediating specificprotein-protein interactions, specifically in the cytoskeleton. |
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•
•
•
•
•
|
Protein Coding Gene |
Type: |
protein_coding_gene |
Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
131
|
Fragment?: |
false |
|
•
•
•
•
•
|
Publication |
First Author: |
Takahashi T |
Year: |
1994 |
Journal: |
Int Immunol |
Title: |
Human Fas ligand: gene structure, chromosomal location and species specificity. |
Volume: |
6 |
Issue: |
10 |
Pages: |
1567-74 |
|
•
•
•
•
•
|
Publication |
First Author: |
Wenzel J |
Year: |
2001 |
Journal: |
FEBS Lett |
Title: |
Multiple interactions of the cytosolic polyproline region of the CD95 ligand: hints for the reverse signal transduction capacity of a death factor. |
Volume: |
509 |
Issue: |
2 |
Pages: |
255-62 |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
279
|
Fragment?: |
false |
|
•
•
•
•
•
|
Publication |
First Author: |
Kirkin V |
Year: |
2007 |
Journal: |
Cell Death Differ |
Title: |
The Fas ligand intracellular domain is released by ADAM10 and SPPL2a cleavage in T-cells. |
Volume: |
14 |
Issue: |
9 |
Pages: |
1678-87 |
|
•
•
•
•
•
|
Publication |
First Author: |
Yankee TM |
Year: |
2001 |
Journal: |
Proc Natl Acad Sci U S A |
Title: |
CD95/Fas induces cleavage of the GrpL/Gads adaptor and desensitization of antigen receptor signaling. |
Volume: |
98 |
Issue: |
12 |
Pages: |
6789-93 |
|
•
•
•
•
•
|
Publication |
First Author: |
Svandova E |
Year: |
2018 |
Journal: |
Front Physiol |
Title: |
FasL Modulates Expression of Mmp2 in Osteoblasts. |
Volume: |
9 |
|
Pages: |
1314 |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
279
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
279
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
279
|
Fragment?: |
false |
|
•
•
•
•
•
|
Publication |
First Author: |
Lynch DH |
Year: |
1995 |
Journal: |
Immunol Today |
Title: |
Fas and FasL in the homeostatic regulation of immune responses. |
Volume: |
16 |
Issue: |
12 |
Pages: |
569-74 |
|
•
•
•
•
•
|
Publication |
First Author: |
Tan S |
Year: |
2019 |
Journal: |
Cell Death Dis |
Title: |
IL-6-driven FasL promotes NF-κBp65/PUMA-mediated apoptosis in portal hypertensive gastropathy. |
Volume: |
10 |
Issue: |
10 |
Pages: |
748 |
|
•
•
•
•
•
|
Publication |
First Author: |
Embree-Ku M |
Year: |
2002 |
Journal: |
Toxicol Pathol |
Title: |
FasL deficiency enhances the development of tumors in p53+/- mice. |
Volume: |
30 |
Issue: |
6 |
Pages: |
705-13 |
|
•
•
•
•
•
|
Publication |
First Author: |
Bernard-Bloch R |
Year: |
2023 |
Journal: |
J Leukoc Biol |
Title: |
Ambivalent role of FasL in murine acute graft-versus-host-disease. |
Volume: |
114 |
Issue: |
3 |
Pages: |
205-211 |
|
•
•
•
•
•
|
Publication |
First Author: |
Apaza Alccayhuaman KA |
Year: |
2021 |
Journal: |
Front Immunol |
Title: |
FasL Is Required for Osseous Healing in Extraction Sockets in Mice. |
Volume: |
12 |
|
Pages: |
678873 |
|
•
•
•
•
•
|
Publication |
First Author: |
He JS |
Year: |
2007 |
Journal: |
J Immunol |
Title: |
CTLs contain and use intracellular stores of FasL distinct from cytolytic granules. |
Volume: |
179 |
Issue: |
4 |
Pages: |
2339-48 |
|
•
•
•
•
•
|
Publication |
First Author: |
Semkova I |
Year: |
2006 |
Journal: |
FASEB J |
Title: |
Overexpression of FasL in retinal pigment epithelial cells reduces choroidal neovascularization. |
Volume: |
20 |
Issue: |
10 |
Pages: |
1689-91 |
|
•
•
•
•
•
|
Publication |
First Author: |
Lau HT |
Year: |
1996 |
Journal: |
Science |
Title: |
Prevention of islet allograft rejection with engineered myoblasts expressing FasL in mice. |
Volume: |
273 |
Issue: |
5271 |
Pages: |
109-12 |
|
•
•
•
•
•
|
Publication |
First Author: |
Wang X |
Year: |
2006 |
Journal: |
Cell Death Differ |
Title: |
Activation of extracellular signal-regulated protein kinase 5 downregulates FasL upon osmotic stress. |
Volume: |
13 |
Issue: |
12 |
Pages: |
2099-108 |
|
•
•
•
•
•
|
Publication |
First Author: |
Schulte M |
Year: |
2007 |
Journal: |
Cell Death Differ |
Title: |
ADAM10 regulates FasL cell surface expression and modulates FasL-induced cytotoxicity and activation-induced cell death. |
Volume: |
14 |
Issue: |
5 |
Pages: |
1040-9 |
|
•
•
•
•
•
|
Publication |
First Author: |
Wang CC |
Year: |
2006 |
Journal: |
Biochem Biophys Res Commun |
Title: |
Mouse lymphomas caused by an intron-splicing donor site deletion of the FasL gene. |
Volume: |
349 |
Issue: |
1 |
Pages: |
50-8 |
|
•
•
•
•
•
|
Publication |
First Author: |
O'Reilly LA |
Year: |
2015 |
Journal: |
Cell Death Differ |
Title: |
Loss of c-REL but not NF-κB2 prevents autoimmune disease driven by FasL mutation. |
Volume: |
22 |
Issue: |
5 |
Pages: |
767-78 |
|
•
•
•
•
•
|
Publication |
First Author: |
Fujikura D |
Year: |
2013 |
Journal: |
PLoS One |
Title: |
Type-I interferon is critical for FasL expression on lung cells to determine the severity of influenza. |
Volume: |
8 |
Issue: |
2 |
Pages: |
e55321 |
|
•
•
•
•
•
|
Publication |
First Author: |
Sato A |
Year: |
2014 |
Journal: |
PLoS One |
Title: |
Involvement of the TNF and FasL produced by CD11b Kupffer cells/macrophages in CCl4-induced acute hepatic injury. |
Volume: |
9 |
Issue: |
3 |
Pages: |
e92515 |
|
•
•
•
•
•
|
Publication |
First Author: |
Cohen PY |
Year: |
2009 |
Journal: |
Am J Respir Cell Mol Biol |
Title: |
Thy1 up-regulates FasL expression in lung myofibroblasts via Src family kinases. |
Volume: |
40 |
Issue: |
2 |
Pages: |
231-8 |
|
•
•
•
•
•
|
Publication |
First Author: |
Embree-Ku M |
Year: |
2002 |
Journal: |
Exp Biol Med (Maywood) |
Title: |
Absence of p53 and FasL has sexually dimorphic effects on both development and reproduction. |
Volume: |
227 |
Issue: |
7 |
Pages: |
545-53 |
|
•
•
•
•
•
|
Publication |
First Author: |
Yao PL |
Year: |
2007 |
Journal: |
J Biol Chem |
Title: |
Transcriptional regulation of FasL expression and participation of sTNF-alpha in response to sertoli cell injury. |
Volume: |
282 |
Issue: |
8 |
Pages: |
5420-31 |
|
•
•
•
•
•
|
Publication |
First Author: |
Legge KL |
Year: |
2005 |
Journal: |
Immunity |
Title: |
Lymph node dendritic cells control CD8+ T cell responses through regulated FasL expression. |
Volume: |
23 |
Issue: |
6 |
Pages: |
649-59 |
|
•
•
•
•
•
|
Publication |
First Author: |
Shanker A |
Year: |
2015 |
Journal: |
Cancer Res |
Title: |
Bortezomib Improves Adoptive T-cell Therapy by Sensitizing Cancer Cells to FasL Cytotoxicity. |
Volume: |
75 |
Issue: |
24 |
Pages: |
5260-72 |
|
•
•
•
•
•
|
Publication |
First Author: |
Gorbachev AV |
Year: |
2010 |
Journal: |
Eur J Immunol |
Title: |
CD4+CD25+ regulatory T cells utilize FasL as a mechanism to restrict DC priming functions in cutaneous immune responses. |
Volume: |
40 |
Issue: |
7 |
Pages: |
2006-15 |
|
•
•
•
•
•
|
Publication |
First Author: |
Mohamood AS |
Year: |
2007 |
Journal: |
Am J Pathol |
Title: |
Protection from autoimmune diabetes and T-cell lymphoproliferation induced by FasL mutation are differentially regulated and can be uncoupled pharmacologically. |
Volume: |
171 |
Issue: |
1 |
Pages: |
97-106 |
|
•
•
•
•
•
|
Publication |
First Author: |
Lin YC |
Year: |
2010 |
Journal: |
Toxicol Sci |
Title: |
FasL gene-deficient mice display a limited disruption in spermatogenesis and inhibition of mono-(2-ethylhexyl) phthalate-induced germ cell apoptosis. |
Volume: |
114 |
Issue: |
2 |
Pages: |
335-45 |
|
•
•
•
•
•
|
Publication |
First Author: |
Chung CS |
Year: |
2001 |
Journal: |
Am J Physiol Gastrointest Liver Physiol |
Title: |
Increased apoptosis in lamina propria B cells during polymicrobial sepsis is FasL but not endotoxin mediated. |
Volume: |
280 |
Issue: |
5 |
Pages: |
G812-8 |
|
•
•
•
•
•
|
Publication |
First Author: |
Schmidt M |
Year: |
2016 |
Journal: |
J Invest Dermatol |
Title: |
Thy-1/β3 Integrin Interaction-Induced Apoptosis of Dermal Fibroblasts Is Mediated by Up-Regulation of FasL Expression. |
Volume: |
136 |
Issue: |
2 |
Pages: |
526-529 |
|
•
•
•
•
•
|
Publication |
First Author: |
Hornick EE |
Year: |
2019 |
Journal: |
J Clin Invest |
Title: |
Dendritic cell NLRC4 regulates influenza A virus-specific CD4 T cell responses through FasL expression. |
Volume: |
129 |
Issue: |
7 |
Pages: |
2888-2897 |
|
•
•
•
•
•
|
Publication |
First Author: |
Villa-Morales M |
Year: |
2010 |
Journal: |
Carcinogenesis |
Title: |
Modulation of the Fas-apoptosis-signalling pathway by functional polymorphisms at Fas, FasL and Fadd and their implication in T-cell lymphoblastic lymphoma susceptibility. |
Volume: |
31 |
Issue: |
12 |
Pages: |
2165-71 |
|
•
•
•
•
•
|
Publication |
First Author: |
Soloviova K |
Year: |
2018 |
Journal: |
Clin Immunol |
Title: |
Both perforin and FasL are required for optimal CD8 T cell control of autoreactive B cells and autoantibody production in parent-into-F1 lupus mice. |
Volume: |
194 |
|
Pages: |
34-42 |
|
•
•
•
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•
|
GO Term |
|
•
•
•
•
•
|
GO Term |
|
•
•
•
•
•
|
GO Term |
|
•
•
•
•
•
|
GO Term |
|
•
•
•
•
•
|
Component |
Name: |
ADAM10-processed FasL form |
|
•
•
•
•
•
|
Component |
Name: |
FasL intracellular domain |
|
•
•
•
•
•
|
Publication |
First Author: |
Nagata S |
Year: |
1995 |
Journal: |
Science |
Title: |
The Fas death factor. |
Volume: |
267 |
Issue: |
5203 |
Pages: |
1449-56 |
|
•
•
•
•
•
|
UniProt Feature |
Begin: |
1 |
Description: |
FasL intracellular domain |
Type: |
chain |
End: |
80 |
|
•
•
•
•
•
|
UniProt Feature |
Begin: |
1 |
Description: |
ADAM10-processed FasL form |
Type: |
chain |
End: |
127 |
|
•
•
•
•
•
|
Publication |
First Author: |
Zhu B |
Year: |
2000 |
Journal: |
Eur J Immunol |
Title: |
Double mutant MRL-lpr/lpr-gld/gld cells fail to trigger lpr-graft-versus-host disease in syngeneic wild-type recipient mice, but can induce wild-type B cells to make autoantibody. |
Volume: |
30 |
Issue: |
6 |
Pages: |
1778-84 |
|
•
•
•
•
•
|
Publication |
First Author: |
Takahashi T |
Year: |
1994 |
Journal: |
Cell |
Title: |
Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. |
Volume: |
76 |
Issue: |
6 |
Pages: |
969-76 |
|
•
•
•
•
•
|
Publication |
First Author: |
Hahne M |
Year: |
1995 |
Journal: |
Int Immunol |
Title: |
Characterization of the non-functional Fas ligand of gld mice. |
Volume: |
7 |
Issue: |
9 |
Pages: |
1381-6 |
|
•
•
•
•
•
|
Publication |
First Author: |
Figgett WA |
Year: |
2013 |
Journal: |
Immunity |
Title: |
The TACI receptor regulates T-cell-independent marginal zone B cell responses through innate activation-induced cell death. |
Volume: |
39 |
Issue: |
3 |
Pages: |
573-83 |
|
•
•
•
•
•
|
Publication |
First Author: |
Tsutsui H |
Year: |
1999 |
Journal: |
Immunity |
Title: |
Caspase-1-independent, Fas/Fas ligand-mediated IL-18 secretion from macrophages causes acute liver injury in mice. |
Volume: |
11 |
Issue: |
3 |
Pages: |
359-67 |
|
•
•
•
•
•
|
Publication |
First Author: |
Mabrouk I |
Year: |
2008 |
Journal: |
Immunity |
Title: |
Prevention of autoimmunity and control of recall response to exogenous antigen by Fas death receptor ligand expression on T cells. |
Volume: |
29 |
Issue: |
6 |
Pages: |
922-33 |
|
•
•
•
•
•
|
Publication |
First Author: |
Hägglöf T |
Year: |
2016 |
Journal: |
Nat Immunol |
Title: |
Neutrophils license iNKT cells to regulate self-reactive mouse B cell responses. |
Volume: |
17 |
Issue: |
12 |
Pages: |
1407-1414 |
|
•
•
•
•
•
|
Publication |
First Author: |
Karray S |
Year: |
2004 |
Journal: |
J Immunol |
Title: |
Complete loss of Fas ligand gene causes massive lymphoproliferation and early death, indicating a residual activity of gld allele. |
Volume: |
172 |
Issue: |
4 |
Pages: |
2118-25 |
|
•
•
•
•
•
|
Publication |
First Author: |
Gregory MS |
Year: |
2011 |
Journal: |
PLoS One |
Title: |
Opposing roles for membrane bound and soluble Fas ligand in glaucoma-associated retinal ganglion cell death. |
Volume: |
6 |
Issue: |
3 |
Pages: |
e17659 |
|
•
•
•
•
•
|
Publication |
First Author: |
Petri S |
Year: |
2006 |
Journal: |
J Neurol Sci |
Title: |
Loss of Fas ligand-function improves survival in G93A-transgenic ALS mice. |
Volume: |
251 |
Issue: |
1-2 |
Pages: |
44-9 |
|
•
•
•
•
•
|
Publication |
First Author: |
Weih F |
Year: |
1996 |
Journal: |
Proc Natl Acad Sci U S A |
Title: |
Apoptosis of nur77/N10-transgenic thymocytes involves the Fas/Fas ligand pathway. |
Volume: |
93 |
Issue: |
11 |
Pages: |
5533-8 |
|
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•
•
•
•
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Publication |
First Author: |
Potter CS |
Year: |
2017 |
Journal: |
Exp Dermatol |
Title: |
Loss of FAS/FASL signalling does not reduce apoptosis in Sharpin null mice. |
Volume: |
26 |
Issue: |
9 |
Pages: |
820-822 |
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•
•
•
•
|
Publication |
First Author: |
Couillard M |
Year: |
2002 |
Journal: |
Cancer Res |
Title: |
c-myc-induced apoptosis in polycystic kidney disease is independent of FasL/Fas interaction. |
Volume: |
62 |
Issue: |
8 |
Pages: |
2210-4 |
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•
•
•
•
|
Publication |
First Author: |
Sata M |
Year: |
2000 |
Journal: |
J Mol Cell Cardiol |
Title: |
Fas ligand-deficient mice display enhanced leukocyte infiltration and intima hyperplasia in flow-restricted vessels. |
Volume: |
32 |
Issue: |
8 |
Pages: |
1395-400 |
|
•
•
•
•
•
|
Publication |
First Author: |
Dittel BN |
Year: |
1999 |
Journal: |
J Immunol |
Title: |
Evidence for Fas-dependent and Fas-independent mechanisms in the pathogenesis of experimental autoimmune encephalomyelitis. |
Volume: |
162 |
Issue: |
11 |
Pages: |
6392-400 |
|
•
•
•
•
•
|
Publication |
First Author: |
Langlois RA |
Year: |
2010 |
Journal: |
J Immunol |
Title: |
Plasmacytoid dendritic cells enhance mortality during lethal influenza infections by eliminating virus-specific CD8 T cells. |
Volume: |
184 |
Issue: |
8 |
Pages: |
4440-6 |
|
•
•
•
•
•
|
Publication |
First Author: |
Waldner H |
Year: |
1997 |
Journal: |
J Immunol |
Title: |
Fas- and FasL-deficient mice are resistant to induction of autoimmune encephalomyelitis. |
Volume: |
159 |
Issue: |
7 |
Pages: |
3100-3 |
|
•
•
•
•
•
|
Publication |
First Author: |
Barreiro R |
Year: |
2004 |
Journal: |
J Immunol |
Title: |
Termination of antigen-specific immunity by CD95 ligand (Fas ligand) and IL-10. |
Volume: |
173 |
Issue: |
3 |
Pages: |
1519-25 |
|
•
•
•
•
•
|
Publication |
First Author: |
Crawford HC |
Year: |
2002 |
Journal: |
J Clin Invest |
Title: |
Matrix metalloproteinase-7 is expressed by pancreatic cancer precursors and regulates acinar-to-ductal metaplasia in exocrine pancreas. |
Volume: |
109 |
Issue: |
11 |
Pages: |
1437-44 |
|
•
•
•
•
•
|
Publication |
First Author: |
Hoek RM |
Year: |
1997 |
Journal: |
J Immunol Methods |
Title: |
Allele-specific PCR analysis for detection of the gld Fas-ligand point mutation. |
Volume: |
210 |
Issue: |
1 |
Pages: |
109-12 |
|
•
•
•
•
•
|
Publication |
First Author: |
Hahne M |
Year: |
1996 |
Journal: |
Eur J Immunol |
Title: |
Activated B cells express functional Fas ligand. |
Volume: |
26 |
Issue: |
3 |
Pages: |
721-4 |
|
•
•
•
•
•
|
Publication |
First Author: |
Kaplan HJ |
Year: |
1999 |
Journal: |
Nat Med |
Title: |
Fas ligand (CD95 ligand) controls angiogenesis beneath the retina. |
Volume: |
5 |
Issue: |
3 |
Pages: |
292-7 |
|
•
•
•
•
•
|
Publication |
First Author: |
Huang X |
Year: |
2011 |
Journal: |
J Dent Res |
Title: |
Tgf-beta-mediated FasL-Fas-Caspase pathway is crucial during palatogenesis. |
Volume: |
90 |
Issue: |
8 |
Pages: |
981-7 |
|
•
•
•
•
•
|
Publication |
First Author: |
Hill RA |
Year: |
2007 |
Journal: |
Mol Cell Neurosci |
Title: |
Fas/FasL-mediated apoptosis in the arcuate nucleus and medial preoptic area of male ArKO mice is ameliorated by selective estrogen receptor alpha and estrogen receptor beta agonist treatment, respectively. |
Volume: |
36 |
Issue: |
2 |
Pages: |
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