Protein FAS

URN urn:agi-llid:355
Name FAS
Description Fas (TNF receptor superfamily member)
Connectivity 1548
Notes 7 of the 13 melanoma cell lines were found to have impaired Fas signalling. Taken together, our results indicate that downregulation of Fas expression and resistance to Fas-mediated apoptosis are frequent in melanoma. 7 of the 13 melanoma cell lines were found to have impaired Fas signalling. Taken together, our results indicate that downregulation of Fas expression and resistance to Fas-mediated apoptosis are frequent in melanoma. A lymphoproliferative disorder could be associated with a CD95 mutation. A novel signaling mechanism shows synergy with anti-CD95 monoclonal antibodies for apoptosis and NF-kappaB nuclear translocation. A review of alternative spliced APO-1 variants and their possible biological roles. A role for the Fas/Fas ligand apoptotic pathway in regulating myeloid progenitor cell kinetics. A significant correlation with differentiation status of the tumor was found for the p53 aberration but not for CD95 expression. A significant increase in p21, p53, and fas mRNA expression were reported in the proximal incompetent veins. Fas overexpression did not correlate with p53 expression level and did not correlate with apoptotic cell number in the vein layers. A20 also protects from Fas/CD95 and significantly blunts natural killer cell-mediated endothelial cell apoptosis by inhibiting caspase 8 activation. ATG-induced apoptosis in T cells involves both Fas and TNF pathways and TNF-alpha is produced much earlier than Fas and FasL expression. Ability of Hsp72 to inhibit Fas-mediated apoptosis is limited to type II cells where involvement of the intrinsic pathway is required for efficient effector caspase activation. Although ischemic liver injury was not serious, due to the short ischemia time, TNFR1 and TRAIL are associated with liver ischemic injury in live-donor liver transplantation but Fas is not. Altogether, these findings reveal that NO inhibits YY1 DNA-binding activity through S-nitrosation and consequently results in upregulation of Fas expression and tumor cell sensitization to Fas-induced apoptosis. An association between -670A > G polymorphism in promoter of FAS protein and the grade of necrosis in periportal areas in patients with chronic hepatitis C. Apoptosis is related to upregulation of apo-1 receptor. Assessment of Bcl-2 and Fas expression at diagnosis in acute leukemia (1) could predict responsiveness to induction chemotherapy in ALL but not in AML. Bax, Bcl-2, fas and Fas-L antigen expression in human seminoma: correlation with the apoptotic index. Bcl-2 may be involved in protecting against CD95-mediated apoptosis of cord blood CD34(+) cell. Butyrate induced apoptosis via the Fas/Fas L system and potentiated Fas-triggered apoptosis in MCF-7 cells. CCR5 mediates Fas- and caspase-8 dependent apoptosis of both uninfected and HIV infected primary human CD4 T cells. CD47 associates with Fas upon its activation and augments Fas-mediated apoptosis. CD95 apoptotic function is regulated by SODD/BAG4. CD95 capping and the subsequent cellular polarization is a ROCK signaling-regulated process that does not correlate with the induction of apoptosis. CD95 death-inducing signaling complex formation and internalization in type I and type II cells occur in lipid rafts, which are a major site of caspase-8 activation. CD95 gene mutations play little if any role in the generation of the pool of plasmablasts from systemic lupus erythematosus patients. CD95 requires different signalling thresholds for induction of apoptosis and activation of NF-kappaB. CD95 was expressed at a higher level on CD45RA+ peripheral T-cells in the fetus than in the adult. CD95, DR4 and DR5 localization in rafts have roles in the toxicity of resveratrol and death receptor ligands in colon carcinoma cells. CD95/Fas binds to the expanded binding surface of the FADD death domain. Cardiomyocyte necrosis and/or apoptosis via activated tumor necrosis factor (TNF) and the Fas/Fas ligand (FasL) system may be related to the development of ongoing myocardial damage. Carriage of the TNFRSF6-670 polymorphism in the neonate was not associated with pre-eclampsia or intrauterine growth restriction. Caspase-10 is recruited to and activated at the native CD95 death-inducing signalling complex in a FADD-dependent manner. Cells expressing Fas mutations from patients with the autoimmune lymphoproliferative syndrome reveals that formation of signaling protein oligomeric transduction structures can be disrupted by distinct mechanisms. Cross-talk between glioma cells and neutrophils through the Fas/FasL system stimulated expression of IL-6 and IL-8 in glioma cells, enhanced neutrophil viability, and stimulated cytokine production in neutrophils. Cytochrome c acts as a catalyst of phosphatidylserine oxidation during Fas-triggered A549 cell apoptosis. Cytochrome c release upon Fas receptor activation. DNA damage, death receptor (CD95) activation and ROS formation contribute to UVB-induced apoptosis in an essential and independent way. Data indicate that the apoptosis program in T cells includes the shedding/secretion of different forms of Fas to spread a death signal. Data show that Fas ligand is expressed on cytotoxic effector and memory cells, suggesting that the Fas/FasL system is involved in the inflammatory process observed in silicosis patients. Data strongly indicate that an increment of soluble FAS/soluble FASL ratio after treatment could be an excellent marker of chemosensitivity in colorectal cancer. Data suggest that frequent Fas gene mutations in nasal natural killer (NK)/T-cell lymphoma (NL) can result in resistance to apoptosis and may contribute to the pathogenesis of NL by adding to the tumor immune privilege. Data suggest that increased intrathecal release of Fas, but not FasL or caspase 3, in the cerebrospinal fluid of infants with hydrocephalus may serve as an indicator of brain injury from progressive ventricular dilatation. Decreased expression of Fas is associated with disease progression in urothelial cancers. Decreased expression of Fas is seen in aggressive tumors and tumors that are poorly differentiated. Deserves further investigation, which may then shed more light on immune escape mechanisms of this tumor and thus enable novel therapeutic strategies. Decreased function of Fas in patients displaying delayed progression of HIV-induced immune deficiency. Delayed elevation of ceramide is proposed to promote necrosis in Fas-stimulated cells where caspase-8 activation was insufficient to trigger caspase-3-dependent apoptosis. Differential expressions of Fas and Fas ligand in human placenta. Dysfunction of the Fas apoptotic signaling pathway in persistent polyclonal B-cell lymphocytosis. Endotoxin-induced lymphopenia was constituted by cells with the highest rates of disappearance were characterized by an activated phenotype (CD45RA(-) CD45RO(+)) as well as a phenotype linked to apoptosis (CD95(+) CD28(-)). Expression of Fas and Fas ligand in esophageal tissue mucosa and carcinomas. Expression of P-glycoprotein does not induce resistance to caspase-8 and -3 activation or anti-Fas-induced cell apoptosis. Expression of a functional Fas death receptor by human foetal motoneurons. FAS expression was induced by interferon-alpha in basal carcinoma cells. FAS germline mutations have been associated with the development of autoimmune lymphoproliferative syndrome (ALPS). FAS-G670A gene polymorphism is associated with the severity of villous atrophy in coeliac disease. FLIP switches Fas-mediated glucose signaling in human pancreatic beta cells from apoptosis to cell replication. Fas activation plays a role in NFkappaB inhibition-induced apoptosis in human tumor cells. Fas and Fas ligand expression are regulated in leukocytes during systemic inflammation. Fas and FasL have roles in progression of breast cancer. Fas defects may play a role in the pathogenesis of mycosis fungoides. Fas engagement increases expression of interleukin-6 in human glioma cells. Fas induces alpha(v)beta(8) integrin in cell migration. Fas is activated in vivo in human epidermis after UVB exposure. Fas is effective in preventing human CD8(+) cytotoxic T lymphocyte-mediated cell killing, which may prevent xenograft rejection. Fas is expressed in ovarian neoplasms, and FasL is upregulated in malignant ovarian neoplasms. Fas is inhibited by FAP-1 in tumor cells. Fas polymorphism is associated with altered apoptotic capacity in lymphocyte cultures, and risk of lung cancer. Fas promoter -670A/G polymorphism was significantly associated with systemic lupus erythematosus (SLE), suggesting a possibility that Fas promoter contributes, at least in part, to the pathogenesis of SLE. Fas resistance of leukemic eosinophils to NF-kappa B activation results from Fas ligation itself and can be negated by inhibition of the nuclear translocation of p65/p50. Fas signaling may have a role in the regulation of endothelial function and blood pressure through modulating endothelial nitric oxide synthase expression in the Akt signal-dependent manner. Fas stimulation may contribute to hepatocellular carcinoma cell survival or proliferation. Fas system as an inducer of apoptosis in cutaneous leishmaniasis. Fas was expressed in sperm of infertile men. Fas, DR4, and DR5 are activated in drug-sensitive cells in response to anticancer drugs depending on the cytotoxic effect of each drug. Fas, Fas ligand (FasL) on activated T lymphocytes induces activation-induced cell death. Fas-670 polymorphism is not associated with inflammatory bowel disease in Chinese patients. Fas-FasL interactions may contribute to mechanisms of neuronal loss and neuritic degeneration in Alzheimer disease. Fas-induced apoptosis of myeloid leukemia cells is restricted to G1 phase of the cell cycle and can be increased by interferon. Fas-induced monocyte cytokine responses are associated with monocyte apoptosis, nuclear translocation of NF-kappa B, and cytokine gene expression and are blocked by caspase inhibition but not by inhibition of IL-1beta signaling. Fas-mediated apoptosis is important in regulating cell replication and death in trisomy 8 hematopoietic cells but not in cells with other cytogenetic abnormalities. Fas-mediated apoptosis is regulated by calmodulin. Fas/CD95 pathway is activated by Ad-p53 in human gliomas. Fas/CD95-induced cell death in Jurkat cells is augmented by exposure to CO via inhibition in the activation of ERK MAPK. Fas/Fas-L and Bcl-2 expression participate in regulation of apoptosis in extravillous trophoblast(EVT) along invasion to decidua. Increased apoptosis in invasive phenotype of EVT may be attributable to increased Fas and Fas-L and decreased Bcl-2. Frequent mutations of Fas gene in nasal NK/T cell lymphoma. Functional promoter haplotypes of FAS are associated with the phenotype of SLE characterized by thrombocytopenia. Further evidence for role of a promoter polymorphism in the TNFRSF6 gene in genetic predisposition to Alzheimer disease. Genetic polymorphisms of Fas (CD95) in human longevity. Glutathione peroxidase-1 protects from apoptosis induced by this antigen. H2O2 induces apoptosis of L02 cells by increasing cytosolic (Ca2+)i, and inducing Fas mRNA and protein expression. HLA class II signals sensitize B lymphocytes to apoptosis via CD95. Human cells transformed with Ad12 demonstrated reduced expression of cell surface Fas antigen. IFN-gamma enhanced constitutive CD95 expression. Coincubation with anti-CD95 monoclonal antibody induced apoptosis. IL-18 and TNF-alpha function both as apoptosis-promoting factors and as apoptosis-inhibiting factors in acute liver failure. Immunohistochemical expression of this protein in squamous cell carcinomas from immunosuppressed renal transplant recipients and immunocompetent individuals. In the case of Fas-mediated apoptosis, when we transiently introduced these hybrid-ribozyme libraries into Fas-expressing HeLa cells, we were able to isolate surviving clones that were resistant to or exhibited a delay in Fas-mediated apoptosis. In this study, we show that c-FLIP(L) but not c-FLIP(S) physically binds to Daxx through interaction between C-terminal domain of c-FLIP(L) and Fas-binding domain of Daxx, an alternative Fas signaling adaptor. Increased expression of Fas antigen on CD4+ subset and increased serum sFas level are valuable markers of clinical activity in multiple sclerosis. Infection of primary cells with adenoviruses carrying the relevant point mutations confirmed the crucial role of putative YXX Phi and dileucine (LL) transport motifs within Ad2 10.4-14.5 for down-regulation of Fas, TRAIL-R1, TRAIL-R2, and EGFR. Interferon-gamma increases its expression in B-leukemia cells. Latent sensitivity to Fas-mediated apoptosis after CD40 ligation may explain activity of CD154 gene therapy in chronic lymphocytic leukemia. Longitudinally obtained data indicate that Fas is upregulated in peripheral blood mononuclear cells of multiple sclerosis patients, especially during secondary progressive course; in relapsing remitting patients Fas levels increase even more dynamically. Lower gene expression of CD95 correlates with detectable blood-brain barrier leakage and active inflammation in the brain as reflected by gadolinium-enhancing lesions on MRI. Mature dendritic cells are protected from Fas/CD95-mediated apoptosis by upregulation of Bcl-X(L). Met sequesters Fas, preventing apoptosis. No role in the CD95L/CD95 pathway for arsennic trioxide-induced apoptosis. Not an effective markers of silent myocardial ischemia in type 2 diabetes. O(6)MeG-triggered apoptosis in proliferating lymphocytes was preceded by a wave of double stranded breaks, which coincided with p53 and Fas receptor upregulation. Our data indicate an association between preterm premature rupture of membranes and increased prevalence of neonatal AG genotype at -670 Fas promoter gene. Our results indicate that Fas-mediated apoptosis is important for endometrial cycling and suggest that dysregulation of the Fas/FasL interactions may have an important role in the development of endometrial cancer. Over-expression of the splice variant Luca-15 inhibited CD95-mediated apoptosis in CEM-C7 T-cells. Overexpression of the mouse Fas gene in human Hep3B hepatoma cells overcomes their resistance to Fas-mediated apoptosis. Ox-LDL dose-dependently up-regulated cell surface Fas expression, determining the degree of apoptosis. Participation of Fas-mediated apoptotic pathway in KB, a human head and neck squamous cell carcinoma cell line, after irradiation. Plasma levels may be a marker for chronic hepatitis C infections. Polymorphisms of the gene encoding Fas have been linked to a variety of autoimmune diseases. Fas gene polymorphisms might be genetic markers for AIH and PBC. REVIEW: Inherited defects in receptor-mediated lymphocyte apoptosis represent a risk factor for lymphomas and somatic mutations of these genes may also play a role in the development and/or progression of lymphomas. Radiation-induced Fas sensitization in prostate cancer cells is mediated through p53-dependent transactivation of the Fas gene, which can be blocked by androgen stimulation mainly through induction of c-jun. Recipient gene polymorphism and acute renal allograft rejection. Regulation of Fas expression by STAT3 and c-Jun is mediated by phosphatidylinositol 3-kinase-AKT signaling. Repression of FAS mRNA expression is the consequence of feedback inhibition of FAS expression by long chain fatty acyl-CoAs, which are formed by FACL3 during its upregulation by vitamin D3 in prostate cancer cells. Review. Fas introduces apoptosis-inducing signals into cells. It is implicated in peripheral lymphocyte regulation, elimination of autoreactive cells, tumors & virus-infected cells, & tissue disruption in autoimmune disease & fulminant hepatitis. SNARK is an NF-kappaB-regulated anti-apoptotic gene that contributes to the tumor-promoting activity of CD95 in apoptosis-resistant tumor cells. Significantly higher soluble form of fas is associated with bile duct carcinoma. Soluble Fas antigen (sFAS) in the serum from patients with adrenal tumors. Soluble HLA class I induces NK cell apoptosis upon the engagement of killer-activating HLA class I receptors through FasL-Fas interaction. Stimulation of CD95 in the presence of caspase inhibitors induces necrosis and expression of various proinflammatory cytokines in primary T lymphocytes, such as TNF-alpha, IFN-gamma and granulocyte/macrophage colony-stimulating factor. Study results do not support hypothesis that AA genotype in FAS gene promoter is engaged in the development of cervical neoplasia. TCR restimulation of activated CD4(+) T cells resulted in Fas translocation into lipid raft microdomains before binding FasL, rendering these cells sensitive to apoptosis. TNF receptor-associated factor 2 (TRAF2) overexpression does not only block apoptosis induction by CD95 antigen but also converts this death receptor into a mediator of invasiveness in pancreatic adenocarcinoma. The A(-670)G polymorphisms in the promoter region of Fas and high levels of sFas are associated with the presence of anti-ganglioside antibodies in Guillain-Barre syndrome. The Fas antigen may be involved in the apoptosis of astrocytic tumors, and the apoptotic index can be a useful parameter for assessing prognosis of astrocytic tumors. The Fas expression is positively correlated with the different degrees of differentiation. The Fas genotype may not appear to be a risk factor for stroke in Korean stroke patients. The Fas signal mediates transcription of IL-10 in Jurkat cells upon contact with glioma cells via a protein kinase A-independent pathway. The apoptotic episodes surrounding the earlier stage of DC differentiation appeared to be mediated by Fas. In contrast, a Fas independent pathway is probably responsible for the apoptotic events associated with terminally differentiated DC. The combination of some polymorphisms of Fas or FasL significantly influenced CD4+ T cell production and viral load decrease, showing that these genes can play a role in the immunoreconstitution triggered by antiretroviral therapy. The extracellular domains of Fas are sufficient to drive membrane FasL-induced formation of supramolecular Fas-FasL complexes, whereas soluble FasL-induced Fas aggregation is dependent on lipid rafts and the intracellular domain of Fas. The fas Receptor Expression was evaluated by flow cytometry. The frequent expression and coexpression of Fas, FasL, and c-FLIP in urothelial carcinomas implicates c-FLIP as an inhibitor of the Fas-FasL-induced death pathway in these tumors. The positive rates of Fas were not significantly different among gallbladder carcinoma, adenoma, dysplasia and chronic cholecystitis. The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contains a death domain. It has been shown to play a central role in the physiological regulation of programmed cell death, and has been implicated in the pathogenesis of various malignancies and diseases of the immune system. The interaction of this receptor with its ligand allows the formation of a death-inducing signaling complex that includes Fas-associated death domain protein (FADD), caspase 8, and caspase 10. The autoproteolytic processing of the caspases in the complex triggers a downstream caspase cascade, and leads to apoptosis. This receptor has been also shown to activate NF-kappaB, MAPK3/ERK1, and MAPK8/JNK, and is found to be involved in transducing the proliferating signals in normal diploid fibroblast and T cells. At least eight alternatively spliced transcript variants encoding seven distinct isoforms have been described. The isoforms lacking the transmembrane domain may negatively regulate the apoptosis mediated by the full length isoform. These results suggest that Fas is involved in neuronal apoptosis in the developing human brain. This review considers the role of the Fas-FasL system as a double-edged sword in the central nervous system: maintaining the immune suppressed status in normal brain and inducing neuronal cell death and inflammation in a variety of neurologic disorders. To evaluate the impact of genetic variations to apoptosis during progression of acquired immunodeficiency syndrome (AIDS), we have performed an extensive genetic analysis of Fas and Fas ligand ( FasL) genes. Tyrosine-based sorting signal in adenovirus RID plays a role in RID's ability to down-regulate FAS and inhibit apoptosis. Vitamin C inhibition of FAS-mediated apoptosis was associated with reduced activity of caspase-3, -8, and -10, as well as diminished levels of ROS and preservation of mitochondrial membrane integrity. We also showed that, in contrast to the stimulation of Fas by an agonistic antibody, Fas aggregation did not occur after irradiation. While short-term activated T cells (two to five rounds of stimulation) are CD95 sensitive and susceptible to activation-induced cell death (AICD), T cells stimulated more than eight times acquire constitutive CD95 resistance and exhibit reduced AICD. A role of Fas gene mutations in the pathogenesis of testicular germ cell tumors. Activation of p38 MAPK and c-Jun N-terminal kinase pathways by hepatitis B virus X protein mediates apoptosis via induction of Fas/FasL and TNFR1/TNFa expression. Alteration associated with nodal metastasis in non-small cell lung cancer. Analysis of Fas-mediated apoptosis in human thyroid epithelial cells. Apoptosis mediated by Fas-FasL and engagement of CTLA-4 are involved in modulation of the immune response in patients infected with Paracoccidioides brasiliensis. Apoptotic effect of Herpesvirus saimiri Tip protein in T cells is mediated by Fas and requires the presence of active Lck in the cell. Association among Gal-1, Fas/Fas ligand-mediated cell death, and the mitochondrial pathway. Autoimmune biliary disease may be mediated by the Fas/FasL apoptotic system. CMet/Fas interaction may inhibit self-association of Fas receptor such that reduced DISC formation occurs in these cells after Fas receptor ligation. cMet/Fas interaction may help explain why endothelial cells are resistant to Fas-mediated apoptosis. Ceramide generation and clustering of CD95 in lipid rafts early in neutrophil apoptosis. Changes in peripheral lymphocyte subsets, and Fas expression in these subsets, during the menstrual cycle. Data suggest that disruption of the cytoskeleton causes apoptosis via activation of CD95 and enhances UV-induced apoptosis, possibly via aiding receptor clustering. Death-inducing capacity of CD95 in Jurkat T cells. Decreased cell-surface expression of Fas and resistance to Fas-mediated apoptosis may occur independently of loss of wt p53 expression in esophageal adenocarcinoma. Deoxycholate induces apoptosis in colon cancer cell lines via a CD95 receptor-independent mechanism. Elevated values of PBMCs apoptosis and Fas both before and 6-7 months after malignant melanonma excision. Epidermal growth factor receptor and CD95 activation are triggered by Src family kinase Yes. Expression associated with apoptosis in sun-exposed keratinocytes. Expression of CD95 in 15/17 human melanoma cell lines analysed, but complete lack of CD95 ligand (CD95L). Expression was significantly increased in neonates with pontosubicular neuron necrosis. Fas Receptors are up-regulated in acute lung injury and the acute respiratory distress syndrome. High level expression in Hepacivirus infected hepatocytes and inversely correlated to number of apoptotis cells. Homeostatic regulation of myelopoiesis in bone marrow is mediated via an autoregulatory feedback loop via the Fas-FasL pathway. In B cells, Gadd45 beta is induced by CD40 through a mechanism that requires NF-kappa B and this induction suppresses Fas-mediated killing. Increased CD95 expression on CD3+ cells and the increased levels of sCD95 in plasma may modify the immunological situation of the recipients after liver transplantation. Increased expression of soluble Fas in pleural effusion associated with lung cancer. Induced il-8 production is activated by activation o the p38 MAPK and ERK1/2 pathways in colonic epithelial cells. Induction of CD95/CD95L expression does not have a role in p53-induced apoptosis. Induction of gene expression by doxorubicin in endothelial cells through a p53-dependent mechanism. Its polymorphism may contributes to the pathogenesis of spondyloarthropathy. Loss of Fas plays an important role in the tumor formation and in the evasion of tumor cells from immune surveillance. Lysosomal degradation by adenovirus E3 RIDalpha protein dependent on specific domains. Maternal serum sFas antigen decreased significantly in the first trimester of pregnancy and at term, possibly affecting immune tolerance and apoptosis for rupture of membranes; amniotic fluid sFas decreased at term compared with the second trimester. Molecular model of a conformational alteration of a mutated extracellular domain of Fas antigen in an adult T cell leukemia cell line. Myelodysplastic syndrome CD34(+)-derived erythroid progenitors underwent abnormal Fas-dependent apoptosis during differentiation that could be responsible for the impaired erythropoiesis. No evidence for an association between the Fas promoter polymorphism at position -670 and Alzheimer's disease. Not a molecular prognostic factor in NSCLC. Oligomerization/depolymerization of soluble Fas antigen can regulate its activity. Possible role of FAS mutations upon higher-grade transformation of FCL to DLBCL was assessed by exmining sequential biopsies; 10 polymorphisms (6 previously unreported) were observed and described. Regulation of transcription by cyclin B1/Cdk1. Results show that IFN-induced up-regulation of Fas sensitizes MM cells to Fas-mediated apoptosis and suggest that attenuation of Stat3 activation may be a potentially important event in this process. Results showed that Fas and/or Fas-Ligand, Bcl-2, and tissue transglutaminase may be involved in apoptotic pathways leading to mucosal atrophy in children with coeliac disease. Results suggest that Fas antigen stimulation not only activates caspase-8, but also a distinct signaling pathway involving protein kinase(s) to induce exposure of the N terminus of Bak protein. SFas promotes a pro-apoptogen effect, which would explain the high susceptibility to apoptosis in active lupus, and that the apoptosis program itself includes release of sFas to spread the death signal. Signals to mitochondria via FADD, caspase-8/10, Bid, and Bax but differentially regulate events downstream from truncated Bid compared to TRAIL receptor 2. Suppression of fas-induced apoptotic signal transduction by thymidine phosphorylase. That H(2)O(2) induces Fas upregulation by promoting cytoplasmic transport of Fas to the cell surface in human airway epithelial cells, and that the activation of the poly(ADP-ribose) polymerase-p53 pathway may be involved in this mechanism. The death effector domain of FADD is involved in interaction with Fas. The importance of the ezrin-to-CD95 linkage in CD95-mediated apoptosis. The inhibitory protein c-FLIP(L) is involved in resistance to CD95-mediated apoptosis in ovarian carcinoma cells with wild-type p53. The lower expression of Fas in urinary malignant cell lines than that in normal cells might be the reason for occurrence and progression of urinary malignant tumors. The role of Fas/Fas ligand (FasL) in tum orgenesis, immune escape, counterattack in colonic cancer. The selective down-regulation of c-FLIP by small interfering RNA oligoribonucleotides was sufficient to sensitize Hodgkin/Reed-Sternberg cells to CD95 and tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. There is no significant contribution of common genetic Fas variants to the genetic risk of developing Hashimoto's thyroiditis or Graves' disease. Thymidylate synthase and p53 have roles in regulating Fas-mediated apoptosis in response to antimetabolites. Trophoblast-cytokine-Fas/FasL triad"" determines the ability of the Fas/FasL system to regulate trophoblast viability. Tumor cell lines expressed cell surface IFN-gamma receptors, and when cultured for 2 days in the presence of IFNG, all exhibited a significant increase in expression of Fas receptors and exhibited intracellular fragmented DNA as a marker of apoptosis. Tumor necrosis factor (alpha)- and Fas-induced apoptosis is blocked by inositol hexakisphosphate in human cells. Tumour-induced mesothelial apoptosis may, in part, be mediated via a Fas-dependent mechanism. Two novel mutations in the Fas receptor gene TNFRSF6 in autoimmune lymphoproliferative syndrome. Upregulation of Fas by IFN-gamma in SNU-638 may accelerate the apoptosis pathway through the Fas and FasL interaction between gastric cancer cells and immune cells. Upregulation of expression by p53 upon genotoxic treatment in human breast tumor cells.

KEGG pathway Type I diabetes mellitus
Apoptosis
Cytokine-cytokine receptor interaction
MAPK signaling pathway

Swiss-Prot Accession P25445
Q5T9P1
Q5T9P3
Q59FU8
Q6ICT6
Q8IUB6
Q8IUB7
Q9UEL0
Q9UET8
P25446
Q6GT31
Q8C350
Q63199
Q9R230
Q5T9P2
Q5T9P0
Q5T9N5
Q5T9N6
Q5T9P4

Unigene ID Hs.244139
Mm.1626
Rn.162521
Mm.392903
Rn.144672

KEGG ID hsa:355
rno:246097
mmu:14102

Swiss-Prot ID TNR6_HUMAN
TNR6_RAT
Q5T9P1_HUMAN
Q5T9P3_HUMAN
Q6GT31_MOUSE
Q8C350_MOUSE

Cell Localization Plasma membrane

GO ID 0042802
0004888
0019724
0008633
0006924
0006916
0010467
0006955
0002377
0008625
0006925
0050869
0045060
0006461
0051260
0045619
0045637
0003014
0051384
0051789
0009636
0007165
0048536
0006927
0005829
0009897
0005576
0016021
0005886
0005625
0005515
0004872
0043029
0006915
0008624
0043066
0043065
0009986
0016020
0005031
0007568
0006917
0042698
0034097
0042493
0043627
0001666
0010035
0032496
0043434
0007283
0005901
0045121
0048471
0042981

Pathway TNFRSF6 -> HSF1 signaling
TNFRSF6 -> FOXO3A signaling
TNFRSF6 -> DDIT3 signaling
TNFR -> NF-kB signaling
TNFR -> AP-1/ATF/TP53 signaling
TNFRSF5/6 -> RB1/E2F signaling
TNFR -> CREB/ELK-SRF signaling
CVD and receptors (all)
CVD and receptors (all) + Ligands
Figure 3 CAR 2009
PPARG Targets
FXR Targets
New Pathway
PPARalpha Pathway

IPI ID IPI00744894
IPI00216357
IPI00216358
IPI00216359
IPI00170811
IPI00291314
IPI00375340
IPI00235003
IPI00748193
IPI00110896
IPI00874636
IPI00206056
IPI00560281
IPI00781030

Ariadne Ontology TNFR

Mouse chromosome position 19 23.0 cM

GO Molecular Function protein binding
identical protein binding
tumor necrosis factor receptor activity
receptor activity
transmembrane receptor activity

Homologene ID 27

Hugo ID 11920

GO Cellular Component extracellular region
cell surface
membrane
soluble fraction
external side of plasma membrane
perinuclear region of cytoplasm
cytosol
plasma membrane
membrane raft
integral to membrane
caveola

MGI ID 95484
2147489

Human chromosome position 10q24.1

GO Biological Process protein complex assembly
protein homooligomerization
negative regulation of B cell activation
negative regulation of apoptosis
anti-apoptosis
positive regulation of apoptosis
induction of apoptosis
induction of apoptosis by extracellular signals
induction of apoptosis via death domain receptors
activation of pro-apoptotic gene products
signal transduction
regulation of lymphocyte differentiation
regulation of myeloid cell differentiation
T cell homeostasis
activation-induced cell death of T cells
negative thymic T cell selection
apoptosis
transformed cell apoptosis
inflammatory cell apoptosis
aging
spleen development
immune response
B cell mediated immunity
immunoglobulin production
gene expression
response to lipopolysaccharide
ovulation cycle
renal system process
spermatogenesis
response to drug
response to inorganic substance
response to protein stimulus
response to toxin
response to cytokine stimulus
response to peptide hormone stimulus
response to estrogen stimulus
response to glucocorticoid stimulus
response to hypoxia

Rat chromosome position 1q52

GenBank ID NC_000010
NM_000043
NP_000034
NM_152872
NP_690611
NM_152871
NP_690610
NM_152873
NP_690612
NM_152874
NP_690613
NM_152875
NP_690614
NM_152877
NP_690616
NM_152876
NP_690615
NT_030059
NW_924884
NW_001838005
AC_000053
AC_000142
AF061978
AAC16237
AJ279011
CAC35539
AJ279012
CAC35540
AJ279013
CAC35541
AJ509179
CAD48929
AJ509180
CAD48930
AJ509181
CAD48931
AJ509182
CAD48932
AL157394
CAI13870
CAI13871
CAI13872
AY450925
AAR08906
CH471066
EAW50147
EAW50148
EAW50149
EAW50150
EAW50151
EAW50152
D31968
BAA20850
AB209361
BAD92598
AK290978
BAF83667
AK311164
AK311424
AK311499
AY495076
AAS76663
BC012479
AAH12479
CR450307
CAG29303
CR625848
FM246457
FM246458
CAR92543
FM246459
CAR92544
M67454
AAA63174
X63717
CAA45250
X83490
X83491
X83492
X83493
X89101
CAA61473
Z47993
CAA88031
Z47994
CAA88032
Z47995
CAA88033
Z66556
Z70519
CAA94430
Z70520
CAA94431
P25445
Q59FU8
Q5T9P1
Q5T9P3
Q6ICT6
Q8IUB6
Q8IUB7
Q9UEL0
Q9UET8
DQ894675
ABM85601
NC_000085
NM_007987
NP_032013
NT_039687
NW_001030643
AC_000041
NM_001146708
AC102285
AJ295702
CAC00638
AJ295703
AJ295704
CH466534
EDL41748
S56485
AAB25700
S56486
S56490
AK002590
BAB22211
AK086933
BAC39766
BC061160
AAH61160
BY348234
DQ846748
ABI24112
DQ846749
ABI24113
L15352
L15353
M83649
AAA37593
P25446
Q6GT31
Q8C350
NC_005100
NM_139194
NP_631933
NW_001084774
NW_047565
AC_000069
AC120570
CH473953
EDM13158
EDM13159
AF104034
AAD20221
CB810875
D26113
BAA05109
Q63199
Q9R230
Q5T9N5
Q5T9N6
Q5T9P0
Q5T9P2
Q5T9P4
BG066923
CAI13866
CAI13869
CAI13867
CAI13868
BG076122
NW_000145
BI076485
BG065122
BG976607

Group TNFR
extracellular region
cell surface
membrane
soluble fraction
external side of plasma membrane
perinuclear region of cytoplasm
cytosol
plasma membrane
membrane raft
integral to membrane
caveola
protein binding
identical protein binding
tumor necrosis factor receptor activity
receptor activity
transmembrane receptor activity
protein complex assembly
protein homooligomerization
negative regulation of B cell activation
negative regulation of apoptosis
anti-apoptosis
positive regulation of apoptosis
induction of apoptosis
induction of apoptosis by extracellular signals
induction of apoptosis via death domain receptors
activation of pro-apoptotic gene products
signal transduction
regulation of lymphocyte differentiation
regulation of myeloid cell differentiation
T cell homeostasis
activation-induced cell death of T cells
negative thymic T cell selection
apoptosis
transformed cell apoptosis
inflammatory cell apoptosis
aging
spleen development
immune response
B cell mediated immunity
immunoglobulin production
gene expression
response to lipopolysaccharide
ovulation cycle
renal system process
spermatogenesis
response to drug
response to inorganic substance
response to protein stimulus
response to toxin
response to cytokine stimulus
response to peptide hormone stimulus
response to estrogen stimulus
response to glucocorticoid stimulus
response to hypoxia

RGD ID 619831

LocusLink ID 355
14102
246097
107133

Alias APT1
CD95
FAS1
APO-1
FASTM
ALPS1A
TNFRSF6
tumor necrosis factor receptor superfamily, member 6
Fas AMA
Fas antigen
CD95 antigen
OTTHUMP00000020045
OTTHUMP00000020046
OTTHUMP00000020051
OTTHUMP00000059646
apoptosis antigen 1
APO-1 cell surface antigen
tumor necrosis factor receptor superfamily member 6
lpr
TNFR6
AI196731
Fas (TNF receptor superfamily member)
lymphoproliferation
Fas
Fas receptor
apo-1 antigen
Fas antigen (ATP1)
apoptosis-mediating surface antigen FAS
apoptosis (APO-1) antigen 1
TNR6
TNR6_HUMAN
apoptosis (APO-1) antigen I
apoptosis antigen I
FASL receptor
Tumor necrosis factor receptor superfamily member 6 precursor
APT I
APO I
sFas
APO-1/FAS
FasR
LOC365454
Fas receptors
FASL receptors
FAS I
lymphoproliferation protein
tumor necrosis factor receptor 6
Fas (TNF receptor superfamily member 6)
LOC368136
lymphoproliferation gene
atp1
tumor necrosis factor receptor superfamily

Organism Homo sapiens
Mus musculus
Rattus norvegicus

OMIM ID 134637
601859