Gene Symbol: Fadd
Description: Fas (TNFRSF6)-associated via death domain
Alias: Mort1/FADD, FAS-associated death domain protein, FAS-associating death domain-containing protein, Fas-associating protein with death domain, mediator of receptor induced toxicity, protein FADD
Species: mouse
Products:     Fadd

Top Publications

  1. Imtiyaz H, Zhang Y, Zhang J. Structural requirements for signal-induced target binding of FADD determined by functional reconstitution of FADD deficiency. J Biol Chem. 2005;280:31360-7 pubmed
    b>FADD is a key adaptor modulating several signaling pathways such as apoptosis induced by Fas (CD95) and tumor necrosis factor receptor 1, and cell proliferation induced by mitogens...
  2. Zhang Y, Rosenberg S, Wang H, Imtiyaz H, Hou Y, Zhang J. Conditional Fas-associated death domain protein (FADD): GFP knockout mice reveal FADD is dispensable in thymic development but essential in peripheral T cell homeostasis. J Immunol. 2005;175:3033-44 pubmed
    Fas-associated death domain protein (FADD)/mediator of receptor-induced toxicity-1 is required for signaling induced by death receptors such as Fas...
  3. Yeh W, de la Pompa J, McCurrach M, Shu H, Elia A, Shahinian A, et al. FADD: essential for embryo development and signaling from some, but not all, inducers of apoptosis. Science. 1998;279:1954-8 pubmed
    b>FADD (also known as Mort-1) is a signal transducer downstream of cell death receptor CD95 (also called Fas)...
  4. Zhuang H, Gan Z, Jiang W, Zhang X, Hua Z. Comparative proteomics analysis reveals roles for FADD in the regulation of energy metabolism and proteolysis pathway in mouse embryonic fibroblast. Proteomics. 2013;13:2398-413 pubmed publisher
    Fas-associated death domain-containing protein (FADD) is a classical apoptotic pathway adaptor. Further studies revealed that it also plays essential roles in nonapoptotic processes, which is assumed to be regulated by its phosphorylation...
  5. Cheng W, Wang L, Zhang R, Du P, Yang B, Zhuang H, et al. Regulation of protein kinase C inactivation by Fas-associated protein with death domain. J Biol Chem. 2012;287:26126-35 pubmed publisher
    ..PKC has been implicated in regulating Fas-associated protein with death domain (FADD), an important adaptor protein involved in regulating death receptor-mediated apoptosis...
  6. Imtiyaz H, Rosenberg S, Zhang Y, Rahman Z, Hou Y, Manser T, et al. The Fas-associated death domain protein is required in apoptosis and TLR-induced proliferative responses in B cells. J Immunol. 2006;176:6852-61 pubmed
    The Fas-associated death domain protein (FADD)/Mort1 is a signaling adaptor protein which mediates the activation of caspase 8 during death receptor-induced apoptosis...
  7. Hsu H, Shu H, Pan M, Goeddel D. TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell. 1996;84:299-308 pubmed
    ..Here we show that TRADD directly interacts with TRAF2 and FADD, signal transducers that activate NF-kappa B and induce apoptosis, respectively...
  8. Alappat E, Feig C, Boyerinas B, Volkland J, Samuels M, Murmann A, et al. Phosphorylation of FADD at serine 194 by CKIalpha regulates its nonapoptotic activities. Mol Cell. 2005;19:321-32 pubmed
    b>FADD is essential for death receptor (DR)-induced apoptosis...
  9. Boldin M, Varfolomeev E, Pancer Z, Mett I, Camonis J, Wallach D. A novel protein that interacts with the death domain of Fas/APO1 contains a sequence motif related to the death domain. J Biol Chem. 1995;270:7795-8 pubmed
    ..Induced expression of the protein results in ligand-independent triggering of cytotoxicity, suggesting that it is involved in cell death induction by Fas/APO1. ..

More Information


  1. Cho Y, Challa S, Moquin D, Genga R, Ray T, Guildford M, et al. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell. 2009;137:1112-23 pubmed publisher
    ..Our findings suggest that RIP3 controls programmed necrosis by initiating the pronecrotic kinase cascade, and that this is necessary for the inflammatory response against virus infections. ..
  2. Thomas L, Henson A, Reed J, Salsbury F, Thorburn A. Direct binding of Fas-associated death domain (FADD) to the tumor necrosis factor-related apoptosis-inducing ligand receptor DR5 is regulated by the death effector domain of FADD. J Biol Chem. 2004;279:32780-5 pubmed
    ..central adaptor molecule for these receptors is the death domain-containing protein Fas-associated death domain (FADD). FADD binds a death domain on a receptor or additional adaptor and recruits caspases to the activated receptor...
  3. Zhang H, Zhou X, McQuade T, Li J, Chan F, Zhang J. Functional complementation between FADD and RIP1 in embryos and lymphocytes. Nature. 2011;471:373-6 pubmed publisher
    b>FADD is a common adaptor shared by several death receptors for signalling apoptosis through recruitment and activation of caspase 8 (refs 1-3). Death receptors are essential for immune homeostasis, but dispensable during embryogenesis...
  4. Zhang J, Winoto A. A mouse Fas-associated protein with homology to the human Mort1/FADD protein is essential for Fas-induced apoptosis. Mol Cell Biol. 1996;16:2756-63 pubmed
    ..predicted protein sequence shows 68% identity and 80% similarity with the sequence of recently described human Mort/FADD. This protein, most likely the mouse homolog of human FADD, associates with Fas in vivo only upon the induction of ..
  5. Zhang J, Cado D, Chen A, Kabra N, Winoto A. Fas-mediated apoptosis and activation-induced T-cell proliferation are defective in mice lacking FADD/Mort1. Nature. 1998;392:296-300 pubmed
    ..b>FADD/Mort1 is a Fas-associated protein that is thought to mediate apoptosis by recruiting the protease caspase-8...
  6. Rosenberg S, Zhang H, Zhang J. FADD deficiency impairs early hematopoiesis in the bone marrow. J Immunol. 2011;186:203-13 pubmed publisher
    Signal transduction mediated by Fas-associated death domain protein (FADD) represents a paradigm of coregulation of apoptosis and cellular proliferation...
  7. Vanlangenakker N, Vanden Berghe T, Bogaert P, Laukens B, Zobel K, Deshayes K, et al. cIAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent reactive oxygen species production. Cell Death Differ. 2011;18:656-65 pubmed publisher
    ..In conclusion, our data indicate that cIAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent ROS production. ..
  8. Osborn S, Diehl G, Han S, Xue L, Kurd N, Hsieh K, et al. Fas-associated death domain (FADD) is a negative regulator of T-cell receptor-mediated necroptosis. Proc Natl Acad Sci U S A. 2010;107:13034-9 pubmed publisher
    ..Given the role of death-receptor adapter protein Fas-associated death domain (FADD) in apoptosis, it is intriguing that T-cell receptor (TCR)-induced proliferation is blocked in FADD-defective T ..
  9. Oberst A, Dillon C, Weinlich R, McCormick L, Fitzgerald P, Pop C, et al. Catalytic activity of the caspase-8-FLIP(L) complex inhibits RIPK3-dependent necrosis. Nature. 2011;471:363-7 pubmed publisher
  10. Dillon C, Oberst A, Weinlich R, Janke L, Kang T, Ben Moshe T, et al. Survival function of the FADD-CASPASE-8-cFLIP(L) complex. Cell Rep. 2012;1:401-7 pubmed
    Caspase-8, the initiator caspase of the death receptor pathway of apoptosis, its adapter molecule, FADD, required for caspase-8 activation, and cFLIPL, a caspase-8-like protein that lacks a catalytic site and blocks caspase-8-mediated ..
  11. Mc Guire C, Volckaert T, Wolke U, Sze M, De Rycke R, Waisman A, et al. Oligodendrocyte-specific FADD deletion protects mice from autoimmune-mediated demyelination. J Immunol. 2010;185:7646-53 pubmed publisher
    ..the mechanism behind ODC apoptosis in EAE, we made use of conditional knockout mice lacking the adaptor protein FADD specifically in ODCs (FADD(ODC-KO))...
  12. Sun H, Gong S, Carmody R, Hilliard A, Li L, Sun J, et al. TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis. Cell. 2008;133:415-26 pubmed publisher
    ..These results establish that TIPE2 is an essential negative regulator of TLR and TCR function, and its selective expression in the immune system prevents hyperresponsiveness and maintains immune homeostasis. ..
  13. Schock S, Young J, He T, Sun Y, Winoto A. Deletion of FADD in macrophages and granulocytes results in RIP3- and MyD88-dependent systemic inflammation. PLoS ONE. 2015;10:e0124391 pubmed publisher
    ..when death receptor-mediated apoptosis is blocked, for example, in stimulated Fas-associated Death Domain (FADD) deficient cells...
  14. Hua Z, Sohn S, Kang C, Cado D, Winoto A. A function of Fas-associated death domain protein in cell cycle progression localized to a single amino acid at its C-terminal region. Immunity. 2003;18:513-21 pubmed
    b>FADD is an adaptor known to transmit apoptotic signals from members of the tumor necrosis factor receptor family. We show here that FADD has a domain implicated in cell proliferation...
  15. Li L, Chen Y, Doan J, Murray J, Molkentin J, Liu Q. Transforming growth factor β-activated kinase 1 signaling pathway critically regulates myocardial survival and remodeling. Circulation. 2014;130:2162-72 pubmed publisher
    ..receptor-1 signaling by regulating the formation of 2 cell death complexes, RIP 1 (receptor-interacting protein 1)-FADD (Fas-associated protein with death domain)-caspase 8 and RIP1-RIP3, a process that is dependent on FADD and caspase ..
  16. Dong S, Liang D, An N, Jia L, Shan Y, Chen C, et al. The role of MAPK and FAS death receptor pathways in testicular germ cell apoptosis induced by lead. Acta Biochim Biophys Sin (Shanghai). 2009;41:800-7 pubmed
    ..In conclusion, K-ras/c-fos and Fas/caspase-3 death signaling receptor pathways were involved in the lead-induced apoptosis of the testicular germ cells in mice. ..
  17. Takahashi K, Kawai T, Kumar H, Sato S, Yonehara S, Akira S. Roles of caspase-8 and caspase-10 in innate immune responses to double-stranded RNA. J Immunol. 2006;176:4520-4 pubmed
    ..These results indicate that caspase-8 and caspase-10 are essential components that mediate NF-kappaB-dependent inflammatory responses in antiviral signaling. ..
  18. Estelles A, Charlton C, Blau H. The phosphoprotein protein PEA-15 inhibits Fas- but increases TNF-R1-mediated caspase-8 activity and apoptosis. Dev Biol. 1999;216:16-28 pubmed
    ..These results show that PEA-15 provides a potential mechanism during development for distinguishing between diverse extracellular death-inducing signals that culminate either in apoptosis or in survival. ..
  19. Zhuang H, Wang X, Zha D, Gan Z, Cai F, Du P, et al. FADD is a key regulator of lipid metabolism. EMBO Mol Med. 2016;8:895-918 pubmed publisher
    b>FADD, a classical apoptotic signaling adaptor, was recently reported to have non-apoptotic functions. Here, we report the discovery that FADD regulates lipid metabolism...
  20. Nam Y, Mani K, Ashton A, Peng C, Krishnamurthy B, Hayakawa Y, et al. Inhibition of both the extrinsic and intrinsic death pathways through nonhomotypic death-fold interactions. Mol Cell. 2004;15:901-12 pubmed
    ..The extrinsic pathway is disrupted by heterotypic interactions between ARC's CARD and the DDs of Fas and FADD, which inhibit Fas-FADD binding and assembly of the death-inducing signaling complex (DISC)...
  21. Chakrabandhu K, Herincs Z, Huault S, Dost B, Peng L, Conchonaud F, et al. Palmitoylation is required for efficient Fas cell death signaling. EMBO J. 2007;26:209-20 pubmed
  22. Los M, Wesselborg S, Schulze Osthoff K. The role of caspases in development, immunity, and apoptotic signal transduction: lessons from knockout mice. Immunity. 1999;10:629-39 pubmed
  23. Kuang A, Diehl G, Zhang J, Winoto A. FADD is required for DR4- and DR5-mediated apoptosis: lack of trail-induced apoptosis in FADD-deficient mouse embryonic fibroblasts. J Biol Chem. 2000;275:25065-8 pubmed
    ..Using the FADD dominant negative molecule, several groups have reached different conclusions with respect to the role of FADD in ..
  24. Aziz M, Sundling K, Dreckschmidt N, Verma A. Protein kinase Cepsilon inhibits UVR-induced expression of FADD, an adaptor protein, linked to both Fas- and TNFR1-mediated apoptosis. J Invest Dermatol. 2009;129:2011-21 pubmed publisher
    ..The adaptor protein FADD is the key component of the death-inducing signaling complex of both Fas and tumor necrosis factor receptor 1...
  25. Gurung P, Anand P, Malireddi R, Vande Walle L, Van Opdenbosch N, Dillon C, et al. FADD and caspase-8 mediate priming and activation of the canonical and noncanonical Nlrp3 inflammasomes. J Immunol. 2014;192:1835-46 pubmed publisher
    ..In this study, we show that loss of FADD or caspase-8 in a RIP3-deficient background, but not RIP3 deficiency alone, hampered transcriptional priming and ..
  26. Newton K, Dugger D, Wickliffe K, Kapoor N, de Almagro M, Vucic D, et al. Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis. Science. 2014;343:1357-60 pubmed publisher
    ..Our data indicate that the kinase activity of RIPK3 is essential for necroptosis but also governs whether a cell activates caspase-8 and dies by apoptosis. ..
  27. Shikama Y, Yamada M, Miyashita T. Caspase-8 and caspase-10 activate NF-kappaB through RIP, NIK and IKKalpha kinases. Eur J Immunol. 2003;33:1998-2006 pubmed
    ..Recently, some death effector domain (DED)-containing proteins, such as FADD and c-FLIP were reported to activate NF-kappaB...
  28. Sakai Y, Sokolowski B. The large conductance calcium-activated potassium channel affects extrinsic and intrinsic mechanisms of apoptosis. J Neurosci Res. 2015;93:745-54 pubmed publisher
    ..coIP) experiments, we show that BK interacts with p53 and fas-associated protein with death domain (FADD) in mouse brain and when overexpressed in a heterologous expression system, such as HEK293 cells...
  29. Zhande R, Dauphinee S, Thomas J, Yamamoto M, Akira S, Karsan A. FADD negatively regulates lipopolysaccharide signaling by impairing interleukin-1 receptor-associated kinase 1-MyD88 interaction. Mol Cell Biol. 2007;27:7394-404 pubmed
    ..b>FADD is an adaptor protein involved in death receptor-mediated apoptosis...
  30. Tourneur L, Mistou S, Michiels F, Devauchelle V, Renia L, Feunteun J, et al. Loss of FADD protein expression results in a biased Fas-signaling pathway and correlates with the development of tumoral status in thyroid follicular cells. Oncogene. 2003;22:2795-804 pubmed
    ..that tumor cells specifically downregulate the multideath receptor adapter Fas-associated death domain (FADD). The regulation of FADD expression occurred only at the protein level...
  31. Berube C, Boucher L, Ma W, Wakeham A, Salmena L, Hakem R, et al. Apoptosis caused by p53-induced protein with death domain (PIDD) depends on the death adapter protein RAIDD. Proc Natl Acad Sci U S A. 2005;102:14314-20 pubmed
    ..Our findings suggest that caspase-2 contributes to PIDD-mediated cell death, but that it is not the sole effector of this pathway. ..
  32. Kabra N, Cado D, Winoto A. A tailless fas-FADD death-effector domain chimera is sufficient to execute Fas function in T cells but not B cells of MRL-lpr/lpr mice. J Immunol. 1999;162:2766-74 pubmed
    ..So far, only Fas-associated death domain protein (FADD), another death domain-containing molecule has been shown to be essential for Fas signals in vivo...
  33. Fan Q, Huang Z, Boucher M, Shang X, Zuo L, Brinks H, et al. Inhibition of Fas-associated death domain-containing protein (FADD) protects against myocardial ischemia/reperfusion injury in a heart failure mouse model. PLoS ONE. 2013;8:e73537 pubmed publisher
    ..The aim of the current study was to test whether FADD could be a potential target of gene therapy in the treatment of heart failure...
  34. Lin J, Kumari S, Kim C, Van T, Wachsmuth L, Polykratis A, et al. RIPK1 counteracts ZBP1-mediated necroptosis to inhibit inflammation. Nature. 2016;540:124-128 pubmed publisher
  35. Rochat Steiner V, Becker K, Micheau O, Schneider P, Burns K, Tschopp J. FIST/HIPK3: a Fas/FADD-interacting serine/threonine kinase that induces FADD phosphorylation and inhibits fas-mediated Jun NH(2)-terminal kinase activation. J Exp Med. 2000;192:1165-74 pubmed
    ..Fas-associated death domain (FADD), which couples Fas to procaspase-8, and Daxx, which couples Fas to the Jun NH(2)-terminal kinase pathway, bind ..
  36. Thapa R, Nogusa S, Chen P, Maki J, Lerro A, Andrake M, et al. Interferon-induced RIP1/RIP3-mediated necrosis requires PKR and is licensed by FADD and caspases. Proc Natl Acad Sci U S A. 2013;110:E3109-18 pubmed publisher
    ..protein (RIP)1/RIP3 kinase-mediated necrosis when the adaptor protein Fas-associated death domain (FADD) is lost or disabled by phosphorylation, or when caspases (e.g., caspase 8) are inactivated...
  37. Yao C, Zhuang H, Cheng W, Lin Y, Du P, Yang B, et al. FADD phosphorylation impaired islet morphology and function. J Cell Physiol. 2015;230:1448-56 pubmed publisher
    ..As a classical adaptor in Fas-FasL signaling, Fas-associated death domain-containing protein (FADD) takes part in many non-apoptosis processes regulated by its phosphorylation...
  38. von Roretz C, Gallouzi I. Protein kinase RNA/FADD/caspase-8 pathway mediates the proapoptotic activity of the RNA-binding protein human antigen R (HuR). J Biol Chem. 2010;285:16806-13 pubmed publisher
    ..staurosporine PKR itself is not phosphorylated, PKR triggers the cleavage of HuR via its downstream effector FADD that in turn activates the caspase-8/caspase-3 pathway...
  39. Xu Y, Wang D, Luo Y, Li W, Shan Y, Tan X, et al. Beta amyloid-induced upregulation of death receptor 6 accelerates the toxic effect of N-terminal fragment of amyloid precursor protein. Neurobiol Aging. 2015;36:157-68 pubmed publisher
    ..These results suggested that APP N-terminal fragments might play neurotoxic roles in Aβ-induced neuronal injuries through cell surface DR6. ..
  40. Zhang X, Dong X, Wang H, Li J, Yang B, Zhang J, et al. FADD regulates thymocyte development at the ?-selection checkpoint by modulating Notch signaling. Cell Death Dis. 2014;5:e1273 pubmed publisher
    Non-apoptotic functions of Fas-associated protein with death domain (FADD) have been implicated in T lineage lymphocytes, but the nature of FADD-dependent non-apoptotic mechanism in early T-cell development has not been completely ..
  41. Kang S, Fernandes Alnemri T, Rogers C, Mayes L, Wang Y, Dillon C, et al. Caspase-8 scaffolding function and MLKL regulate NLRP3 inflammasome activation downstream of TLR3. Nat Commun. 2015;6:7515 pubmed publisher
    ..TLR3 binding to dsRNA promotes post-translational inflammasome activation through intermediate and late TRIF/RIPK1/FADD-dependent pathways. Both pathways require the scaffolding but not the catalytic function of caspase-8 or RIPK1...
  42. Bossaller L, Chiang P, Schmidt Lauber C, Ganesan S, Kaiser W, Rathinam V, et al. Cutting edge: FAS (CD95) mediates noncanonical IL-1? and IL-18 maturation via caspase-8 in an RIP3-independent manner. J Immunol. 2012;189:5508-12 pubmed publisher
    ..Hence, Fas controls a novel noncanonical IL-1? activation pathway in myeloid cells, which could play an essential role in inflammatory processes, tumor surveillance, and control of infectious diseases. ..
  43. Baker S, Reddy E. Modulation of life and death by the TNF receptor superfamily. Oncogene. 1998;17:3261-70 pubmed
    ..Isolation and characterization of death domain containing proteins (TRADD, FADD/MORT-1, RIP), TRAF domain containing proteins (TRAF1-6) as well as new members and adaptor proteins such as DAXX ..
  44. Chaneva S, Schneider G, Siegmund D, Wajant H, Mages J, Hacker G. Enhanced basal AP-1 activity and de-regulation of numerous genes in T cells transgenic for a dominant interfering mutant of FADD/MORT1. Eur J Immunol. 2004;34:3006-15 pubmed
    The essential role of FADD/MORT1 and caspase-8 in 'death-receptor'-induced apoptosis is well characterized. Surprisingly, these proteins also play a critical role in antigen- or mitogen-induced activation and proliferation of T cells...
  45. Tourneur L, Mistou S, Schmitt A, Chiocchia G. Adenosine receptors control a new pathway of Fas-associated death domain protein expression regulation by secretion. J Biol Chem. 2008;283:17929-38 pubmed publisher
    b>FADD is the key adaptor transmitting the apoptotic signal mediated by death receptors. We have previously shown that FADD protein expression could be lost in vivo in cancerous cells, in mice and humans, and be used as prognostic factor...
  46. Justo P, Sanz A, Lorz C, Egido J, Ortiz A. Lethal activity of FADD death domain in renal tubular epithelial cells. Kidney Int. 2006;69:2205-11 pubmed
    Fas-associated death domain (FADD) is an adaptor protein that is required for the transmission of the death signal from lethal receptors of the tumor necrosis factor superfamily...
  47. Welz P, Wullaert A, Vlantis K, Kondylis V, Fernández Majada V, Ermolaeva M, et al. FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation. Nature. 2011;477:330-4 pubmed publisher
    ..Here we show that mice with IEC-specific knockout of FADD (FADD(IEC-KO)), an adaptor protein required for death-receptor-induced apoptosis, spontaneously developed ..
  48. Schuchmann M, Ruckert F, Garcia Lazaro J, Karg A, Burg J, Knorr N, et al. MORT1/FADD is involved in liver regeneration. World J Gastroenterol. 2005;11:7248-53 pubmed
    ..We used transgenic mice expressing an N-terminal truncated form of MORT1/FADD under the control of the albumin promoter...
  49. Schlicher L, Wissler M, Preiss F, Brauns Schubert P, Jakob C, Dumit V, et al. SPATA2 promotes CYLD activity and regulates TNF-induced NF-?B signaling and cell death. EMBO Rep. 2016;17:1485-1497 pubmed
    ..Thus, this study identifies SPATA2 as an important factor in the TNF signaling pathway with a substantial role for the effects mediated by the cytokine. ..
  50. Balachandran S, Venkataraman T, Fisher P, Barber G. Fas-associated death domain-containing protein-mediated antiviral innate immune signaling involves the regulation of Irf7. J Immunol. 2007;178:2429-39 pubmed
    ..Previously, we had reported on a role for Fas-associated death domain-containing protein (FADD) in the control of TLR-independent innate immune responses to virus infection...
  51. Lin Y, Choksi S, Shen H, Yang Q, Hur G, Kim Y, et al. Tumor necrosis factor-induced nonapoptotic cell death requires receptor-interacting protein-mediated cellular reactive oxygen species accumulation. J Biol Chem. 2004;279:10822-8 pubmed
    ..and found that tumor necrosis factor receptor (TNFR) I mediates TNF-induced necrotic cell death, and that RIP, FADD, and TRAF2 are critical components of the signaling cascade of this TNF-induced necrotic cell death...
  52. O Reilly L, Divisekera U, Newton K, Scalzo K, Kataoka T, Puthalakath H, et al. Modifications and intracellular trafficking of FADD/MORT1 and caspase-8 after stimulation of T lymphocytes. Cell Death Differ. 2004;11:724-36 pubmed
    The adaptor protein FADD/MORT1 is essential for apoptosis induced by 'death receptors', such as Fas (APO-1/CD95), mediating aggregation and autocatalytic activation of caspase-8...
  53. Zaman M, Nomura T, Takagi T, Okamura T, Jin W, Shinagawa T, et al. Ubiquitination-deubiquitination by the TRIM27-USP7 complex regulates tumor necrosis factor alpha-induced apoptosis. Mol Cell Biol. 2013;33:4971-84 pubmed publisher
    ..Our findings indicate that the ubiquitination-deubiquitination cascade mediated by the TRIM27-USP7 complex plays an important role in TNF-?-induced apoptosis. ..
  54. Vanlangenakker N, Bertrand M, Bogaert P, Vandenabeele P, Vanden Berghe T. TNF-induced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members. Cell Death Dis. 2011;2:e230 pubmed publisher
    ..Finally, we also report RIP1-independent but RIP3-mediated necroptosis in the context of TNF signaling in particular conditions. ..
  55. Balachandran S, Thomas E, Barber G. A FADD-dependent innate immune mechanism in mammalian cells. Nature. 2004;432:401-5 pubmed
    ..Here, we report that mammalian cells lacking the death-domain-containing protein FADD are defective in intracellular dsRNA-activated gene expression, including production of type I (alpha/beta) ..
  56. Colussi P, Kumar S. Targeted disruption of caspase genes in mice: what they tell us about the functions of individual caspases in apoptosis. Immunol Cell Biol. 1999;77:58-63 pubmed
    ..The present review discusses these recent findings and elaborates on how these mutant mouse models have helped the understanding of the mechanisms that govern programmed cell death in the immune and other systems. ..
  57. Matsuda N, Teramae H, Yamamoto S, Takano K, Takano Y, Hattori Y. Increased death receptor pathway of apoptotic signaling in septic mouse aorta: effect of systemic delivery of FADD siRNA. Am J Physiol Heart Circ Physiol. 2010;298:H92-101 pubmed publisher
    ..Furthermore, marked increases in the mRNA and protein levels of Fas-associated death domain (FADD), an adaptor molecule to recruit procaspase-8 into the death-inducing signal complex, were observed in septic aorta,..
  58. Sun J, Hilliard B, Xu L, Chen Y. Essential roles of the Fas-associated death domain in autoimmune encephalomyelitis. J Immunol. 2005;175:4783-8 pubmed
    The Fas-associated death domain (FADD) protein mediates apoptosis by coupling death receptors with the caspase cascade. Paradoxically, it also promotes cell mitosis through its C-terminal region...
  59. De Paepe M, Mao Q, Embree Ku M, Rubin L, Luks F. Fas/FasL-mediated apoptosis in perinatal murine lungs. Am J Physiol Lung Cell Mol Physiol. 2004;287:L730-42 pubmed
    ..The developmental time dependence of apoptosis-related events in the murine model should facilitate investigations of the regulation of perinatal pulmonary apoptotic gene expression. ..
  60. Wertz I, Newton K, Seshasayee D, Kusam S, Lam C, Zhang J, et al. Phosphorylation and linear ubiquitin direct A20 inhibition of inflammation. Nature. 2015;528:370-5 pubmed publisher
    ..Collectively, our studies reveal molecular mechanisms whereby A20 deubiquitinase activity and ubiquitin binding, linear ubiquitination, and cellular kinases cooperate to regulate inflammation and cell death. ..
  61. O FLAHERTY J, Mei Y, Freer M, Weyman C. Signaling through the TRAIL receptor DR5/FADD pathway plays a role in the apoptosis associated with skeletal myoblast differentiation. Apoptosis. 2006;11:2103-13 pubmed
    ..Expression of a dominant-negative mutant of the adapter protein FADD also abrogated apoptosis, implicating a death ligand pathway...
  62. Ugolini G, Raoul C, Ferri A, Haenggeli C, Yamamoto Y, Salaün D, et al. Fas/tumor necrosis factor receptor death signaling is required for axotomy-induced death of motoneurons in vivo. J Neurosci. 2003;23:8526-31 pubmed
    ..and pathological situations, we used several mutant mice deficient for Fas signaling and made a novel transgenic FADD-DN (FAS-associated death domain-dominant-negative) strain...
  63. Dannappel M, Vlantis K, Kumari S, Polykratis A, Kim C, Wachsmuth L, et al. RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. Nature. 2014;513:90-4 pubmed publisher
    ..Epithelial FADD ablation inhibited IEC apoptosis and prevented the premature death of mice with IEC-specific RIPK1 knockout...
  64. Ranjan K, Pathak C. Expression of FADD and cFLIPL balances mitochondrial integrity and redox signaling to substantiate apoptotic cell death. Mol Cell Biochem. 2016;422:135-150 pubmed
    b>FADD and cFLIP both are pivotal components of death receptor signaling. The cellular signaling of apoptosis accomplished with death receptors and mitochondria follows independent pathways for cell death...
  65. Newton K, Wickliffe K, Maltzman A, Dugger D, Strasser A, Pham V, et al. RIPK1 inhibits ZBP1-driven necroptosis during development. Nature. 2016;540:129-133 pubmed publisher
    ..Collectively, these findings indicate that the RHIM of RIPK1 is critical for preventing ZBP1/RIPK3/MLKL-dependent necroptosis during development. ..
  66. Begović L, Antunovic M, Matić I, Furcic I, Baričević A, Vojvoda Parcina V, et al. Effect of UVC radiation on mouse fibroblasts deficient for FAS-associated protein with death domain. Int J Radiat Biol. 2016;92:475-82 pubmed publisher
    ..The extrinsic pathway is coupled to a FAS-associated protein with death domain (FADD), an adaptor protein molecule necessary for mediating apoptotic signals through the cell...
  67. Wiegmann K, Schwandner R, Krut O, Yeh W, Mak T, Kronke M. Requirement of FADD for tumor necrosis factor-induced activation of acid sphingomyelinase. J Biol Chem. 1999;274:5267-70 pubmed
    ..In particular, the TNF-R55-associated protein FADD seems to be responsible for recruitment and subsequent activation of caspase 8...
  68. Fernández Majada V, Welz P, Ermolaeva M, Schell M, Adam A, Dietlein F, et al. The tumour suppressor CYLD regulates the p53 DNA damage response. Nat Commun. 2016;7:12508 pubmed publisher
    ..Collectively, our results identify CYLD as a deubiquitinase facilitating DNA damage-induced p53 activation and suggest that regulation of p53 responses to genotoxic stress contributes to the tumour suppressor function of CYLD. ..
  69. Fan C, Pu W, Wu X, Zhang X, He L, Zhou B, et al. Lack of FADD in Tie-2 expressing cells causes RIPK3-mediated embryonic lethality. Cell Death Dis. 2016;7:e2351 pubmed publisher
  70. Zhang R, Wang L, He L, Yang B, Yao C, Du P, et al. Fas-Associated Protein with Death Domain Regulates Notch Signaling during Muscle Regeneration. Cells Tissues Organs. 2014;200:253-64 pubmed publisher
    ..In the present study, we show that a constitutively phosphoryl-mimicking mutation of Fas-associated death domain (FADD-D) enhances Notch-1 signaling and compromises Wnt signaling in both cultured myoblasts and regenerating muscles, ..
  71. Imtiyaz H, Zhou X, Zhang H, Chen D, Hu T, Zhang J. The death domain of FADD is essential for embryogenesis, lymphocyte development, and proliferation. J Biol Chem. 2009;284:9917-26 pubmed publisher
    The Fas-associated death domain-containing protein (FADD) is an adaptor for relaying apoptotic signals initiated by death receptors such as Fas...
  72. Ehlken H, Krishna Subramanian S, Ochoa Callejero L, Kondylis V, Nadi N, Straub B, et al. Death receptor-independent FADD signalling triggers hepatitis and hepatocellular carcinoma in mice with liver parenchymal cell-specific NEMO knockout. Cell Death Differ. 2014;21:1721-32 pubmed publisher
    ..Here we show that hepatitis and HCC development in NEMO(LPC-KO) mice is triggered by death receptor-independent FADD-mediated hepatocyte apoptosis...
  73. Lu J, Weist B, van Raam B, Marro B, Nguyen L, Srinivas P, et al. Complementary roles of Fas-associated death domain (FADD) and receptor interacting protein kinase-3 (RIPK3) in T-cell homeostasis and antiviral immunity. Proc Natl Acad Sci U S A. 2011;108:15312-7 pubmed publisher
    ..Indeed, following mitogenic stimulation, T cells lacking casp8 or its adaptor protein FADD (Fas-associated death domain protein) develop a hyperautophagic morphology, and die a programmed necrosis-like ..
  74. Ho C, Rideout H, Ribe E, Troy C, Dauer W. The Parkinson disease protein leucine-rich repeat kinase 2 transduces death signals via Fas-associated protein with death domain and caspase-8 in a cellular model of neurodegeneration. J Neurosci. 2009;29:1011-6 pubmed publisher
    ..We report that LRRK2 interacts with the death adaptor Fas-associated protein with death domain (FADD), and that in primary neuronal culture LRRK2-mediated neurodegeneration is prevented by the functional inhibition ..
  75. Thorburn J, Moore F, Rao A, Barclay W, Thomas L, Grant K, et al. Selective inactivation of a Fas-associated death domain protein (FADD)-dependent apoptosis and autophagy pathway in immortal epithelial cells. Mol Biol Cell. 2005;16:1189-99 pubmed
    ..The pathway can be activated by the Fas-associated death domain (FADD) of the adaptor protein but is distinct from the known mechanism of FADD-induced apoptosis through caspase-8...
  76. Richards N, Schaner P, Diaz A, Stuckey J, Shelden E, Wadhwa A, et al. Interaction between pyrin and the apoptotic speck protein (ASC) modulates ASC-induced apoptosis. J Biol Chem. 2001;276:39320-9 pubmed
    ..These findings link pyrin to apoptosis pathways and suggest that the modulation of cell survival may be a component of the pathophysiology of familial Mediterranean fever. ..
  77. Bonnet M, Preukschat D, Welz P, Van Loo G, Ermolaeva M, Bloch W, et al. The adaptor protein FADD protects epidermal keratinocytes from necroptosis in vivo and prevents skin inflammation. Immunity. 2011;35:572-82 pubmed publisher
    ..Here, we show that epidermal keratinocyte-restricted deficiency of the adaptor protein FADD (FADD(E-KO)) induced severe inflammatory skin lesions in mice...
  78. Lohmann C, Muschaweckh A, Kirschnek S, Jennen L, Wagner H, Hacker G. Induction of tumor cell apoptosis or necrosis by conditional expression of cell death proteins: analysis of cell death pathways and in vitro immune stimulatory potential. J Immunol. 2009;182:4538-46 pubmed publisher
    ..In one cell line, the induction of Bim(S) induced rapid apoptosis, in the other line the induction of the FADD death domain induced nonapoptotic/necrotic cell death...
  79. Osborn S, Sohn S, Winoto A. Constitutive phosphorylation mutation in Fas-associated death domain (FADD) results in early cell cycle defects. J Biol Chem. 2007;282:22786-92 pubmed
    Fas-associated death domain (FADD) is an adaptor molecule for the death receptor subfamily of the tumor necrosis factor receptor superfamily, but it is also required for cell proliferation...
  80. Mack A, Hacker G. Inhibition of caspase or FADD function blocks proliferation but not MAP kinase-activation and interleukin-2-production during primary stimulation of T cells. Eur J Immunol. 2002;32:1986-92 pubmed
    ..expressing a dominant negative mutant of the caspase-adaptor Fas-associated molecule with death domain (FADD)/MORT1 displayed the same pattern of reaction, i.e. a reduced proliferative response but normal IL-2-production...
  81. Moriwaki K, Balaji S, Bertin J, Gough P, Chan F. Distinct Kinase-Independent Role of RIPK3 in CD11c+ Mononuclear Phagocytes in Cytokine-Induced Tissue Repair. Cell Rep. 2017;18:2441-2451 pubmed publisher
    ..Thus, a key physiological function of RIPK3 is to promote reparative cytokine expression through intestinal CD11c+ MNPs in a kinase- and necroptosis-independent manner. ..
  82. Kondylis V, Polykratis A, Ehlken H, Ochoa Callejero L, Straub B, Krishna Subramanian S, et al. NEMO Prevents Steatohepatitis and Hepatocellular Carcinoma by Inhibiting RIPK1 Kinase Activity-Mediated Hepatocyte Apoptosis. Cancer Cell. 2015;28:582-598 pubmed publisher
    ..Collectively, these results show that NEMO prevents hepatocarcinogenesis by inhibiting RIPK1 kinase activity-driven hepatocyte apoptosis through NF-κB-dependent and -independent functions. ..
  83. Berglund H, Olerenshaw D, Sankar A, Federwisch M, McDonald N, Driscoll P. The three-dimensional solution structure and dynamic properties of the human FADD death domain. J Mol Biol. 2000;302:171-88 pubmed
    b>FADD (also known as MORT-1) is an essential adapter protein that couples the transmembrane receptors Fas (CD95) and tumor necrosis factor receptor-1 (TNF-R1) to intracellular cysteine proteases known as caspases, which propagate and ..