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Reliable, easy-to-read patient information on common medical conditions β€” written in plain language, free of jargon, and grounded in current evidence. Browse the most frequent diagnoses, understand what they mean for everyday life, and learn which steps and questions help you have a focused conversation with your doctor.

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Tumor necrosis factor receptor 1

Introduction

Tumor necrosis factor receptor 1 (TNFR1), also known as tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) and CD120a, is a ubiquitous membrane receptor that binds tumor necrosis factor-alpha (TNFΞ±).[1][2][3]

Function

Function

The protein encoded by this gene is a member of the tumor necrosis factor receptor superfamily, which also contains TNFRSF1B. This protein is one of the major receptors for the tumor necrosis factor-alpha. This receptor can activate the transcription factor NF-ΞΊB, mediate apoptosis, and function as a regulator of inflammation. Antiapoptotic protein BCL2-associated athanogene 4 (BAG4/SODD) and adaptor proteins TRADD and TRAF2 have been shown to interact with this receptor, and thus play regulatory roles in the signal transduction mediated by the receptor.[4]

Clinical significance

Clinical significance

Germline mutations of the extracellular domains of this receptor were found to be associated with the human genetic disorder called tumor necrosis factor associated periodic syndrome (TRAPS) or periodic fever syndrome.[5] Impaired receptor clearance is thought to be a mechanism of the disease.

Mutations in the TNFRSF1A gene is associated with elevated risk of multiple sclerosis.[6]

Serum levels of TNFRSF1A are elevated in schizophrenia and bipolar disorder,[7] and high levels are associated with more severe psychotic symptoms.[8]

High serum levels is also associated with cognitive impairment and dementia.[9][10]

Interactions

Interactions

TNFRSF1A has been shown to interact with:

See also

See also

References

References

  1. ↑ Baker E, Chen LZ, Smith CA, Callen DF, Goodwin R, Sutherland GR (November 1991). “Chromosomal location of the human tumor necrosis factor receptor genes”. Cytogenet Cell Genet. 57 (2–3): 117–8. doi:10.1159/000133127. PMIDΒ 1655358.
  2. ↑ Schall TJ, Lewis M, Koller KJ, Lee A, Rice GC, Wong GH, Gatanaga T, Granger GA, Lentz R, Raab H, et al. (June 1990). “Molecular cloning and expression of a receptor for human tumor necrosis factor”. Cell. 61 (2): 361–70. doi:10.1016/0092-8674(90)90816-W. PMIDΒ 2158863.
  3. ↑ Offermanns, Stefan; Rosenthal, Walter (2008). Encyclopedia of Molecular Pharmacology, Vol. 1 (2nd ed.). Heidelberg, Germany: Springer. p.Β 1248.
  4. ↑ “Entrez Gene: TNFRSF1A tumor necrosis factor receptor superfamily, member 1A”.
  5. ↑ KΓΌmpfel T, Hohlfeld R (October 2009). “Multiple sclerosis. TNFRSF1A, TRAPS and multiple sclerosis”. Nat Rev Neurol. 5 (10): 528–9. doi:10.1038/nrneurol.2009.154. PMIDΒ 19794511.
  6. ↑ “The genetic association of variants in CD6, TNFRSF1A and IRF8 to multiple sclerosis: a multicenter case-control study”. PLoS ONE. 6 (4): e18813. 2011. doi:10.1371/journal.pone.0018813. PMCΒ 3084233. PMIDΒ 21552549.
  7. ↑ Hope S, Melle I, Aukrust P, Steen NE, Birkenaes AB, Lorentzen S, Agartz I, Ueland T, Andreassen OA (November 2009). “Similar immune profile in bipolar disorder and schizophrenia: selective increase in soluble tumor necrosis factor receptor I and von Willebrand factor”. Bipolar Disord. 11 (7): 726–34. doi:10.1111/j.1399-5618.2009.00757.x. PMIDΒ 19839997.
  8. ↑ Hope S, Ueland T, Steen NE, Dieset I, Lorentzen S, Berg AO, Agartz I, Aukrust P, Andreassen OA (April 2013). “Interleukin 1 receptor antagonist and soluble tumor necrosis factor receptor 1 are associated with general severity and psychotic symptoms in schizophrenia and bipolar disorder”. Schizophr. Res. 145 (1–3): 36–42. doi:10.1016/j.schres.2012.12.023. PMIDΒ 23403415.
  9. ↑ Buchhave P, Zetterberg H, Blennow K, Minthon L, Janciauskiene S, Hansson O (November 2010). “Soluble TNF receptors are associated with AΞ² metabolism and conversion to dementia in subjects with mild cognitive impairment”. Neurobiol. Aging. 31 (11): 1877–84. doi:10.1016/j.neurobiolaging.2008.10.012. PMIDΒ 19070941.
  10. ↑ Diniz BS, Teixeira AL, Ojopi EB, Talib LL, MendonΓ§a VA, Gattaz WF, Forlenza OV (2010). “Higher serum sTNFR1 level predicts conversion from mild cognitive impairment to Alzheimer’s disease”. J. Alzheimers Dis. 22 (4): 1305–11. doi:10.3233/JAD-2010-100921. PMIDΒ 20930310.
  11. ↑ 11.0 11.1 Jiang Y, Woronicz JD, Liu W, Goeddel DV (1999). “Prevention of constitutive TNF receptor 1 signaling by silencer of death domains”. Science. 283 (5401): 543–6. doi:10.1126/science.283.5401.543. PMIDΒ 9915703.
  12. ↑ Miki K, Eddy EM (2002). “Tumor necrosis factor receptor 1 is an ATPase regulated by silencer of death domain”. Mol. Cell. Biol. 22 (8): 2536–43. doi:10.1128/MCB.22.8.2536-2543.2002. PMCΒ 133739. PMIDΒ 11909948.
  13. ↑ 13.0 13.1 Gajate C, Mollinedo F (2005). “Cytoskeleton-mediated death receptor and ligand concentration in lipid rafts forms apoptosis-promoting clusters in cancer chemotherapy”. J. Biol. Chem. 280 (12): 11641–7. doi:10.1074/jbc.M411781200. PMIDΒ 15659383.
  14. ↑ Vincenz C, Dixit VM (1997). “Fas-associated death domain protein interleukin-1beta-converting enzyme 2 (FLICE2), an ICE/Ced-3 homologue, is proximally involved in CD95- and p55-mediated death signaling”. J. Biol. Chem. 272 (10): 6578–83. doi:10.1074/jbc.272.10.6578. PMIDΒ 9045686.
  15. ↑ 15.0 15.1 15.2 Hsu H, Shu HB, Pan MG, Goeddel DV (1996). “TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways”. Cell. 84 (2): 299–308. doi:10.1016/S0092-8674(00)80984-8. PMIDΒ 8565075.
  16. ↑ Zhang SQ, Kovalenko A, Cantarella G, Wallach D (2000). “Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation”. Immunity. 12 (3): 301–11. doi:10.1016/S1074-7613(00)80183-1. PMIDΒ 10755617.
  17. ↑ Chaudhary PM, Eby MT, Jasmin A, Kumar A, Liu L, Hood L (2000). “Activation of the NF-kappaB pathway by caspase 8 and its homologs”. Oncogene. 19 (39): 4451–60. doi:10.1038/sj.onc.1203812. PMIDΒ 11002417.
  18. ↑ 18.0 18.1 Guo D, Dunbar JD, Yang CH, Pfeffer LM, Donner DB (1998). “Induction of Jak/STAT signaling by activation of the type 1 TNF receptor”. J. Immunol. 160 (6): 2742–50. PMIDΒ 9510175.
  19. ↑ Miscia S, Marchisio M, Grilli A, Di Valerio V, Centurione L, Sabatino G, Garaci F, Zauli G, Bonvini E, Di Baldassarre A (2002). “Tumor necrosis factor alpha (TNF-alpha) activates Jak1/Stat3-Stat5B signaling through TNFR-1 in human B cells”. Cell Growth Differ. 13 (1): 13–8. PMIDΒ 11801527.
  20. ↑ Castellino AM, Parker GJ, Boronenkov IV, Anderson RA, Chao MV (1997). “A novel interaction between the juxtamembrane region of the p55 tumor necrosis factor receptor and phosphatidylinositol-4-phosphate 5-kinase”. J. Biol. Chem. 272 (9): 5861–70. doi:10.1074/jbc.272.9.5861. PMIDΒ 9038203.
  21. ↑ Boldin MP, Mett IL, Wallach D (1995). “A protein related to a proteasomal subunit binds to the intracellular domain of the p55 TNF receptor upstream to its ‘death domain‘“. FEBS Lett. 367 (1): 39–44. doi:10.1016/0014-5793(95)00534-G. PMIDΒ 7601280.
  22. ↑ Dunbar JD, Song HY, Guo D, Wu LW, Donner DB (1997). “Two-hybrid cloning of a gene encoding TNF receptor-associated protein 2, a protein that interacts with the intracellular domain of the type 1 TNF receptor: identity with subunit 2 of the 26S protease”. J. Immunol. 158 (9): 4252–9. PMIDΒ 9126987.
  23. ↑ 23.0 23.1 23.2 Hsu H, Huang J, Shu HB, Baichwal V, Goeddel DV (1996). “TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex”. Immunity. 4 (4): 387–96. doi:10.1016/S1074-7613(00)80252-6. PMIDΒ 8612133.
  24. ↑ Kim JW, Choi EJ, Joe CO (2000). “Activation of death-inducing signaling complex (DISC) by pro-apoptotic C-terminal fragment of RIP”. Oncogene. 19 (39): 4491–9. doi:10.1038/sj.onc.1203796. PMIDΒ 11002422.
  25. ↑ Duan H, Dixit VM (1997). “RAIDD is a new ‘death’ adaptor molecule”. Nature. 385 (6611): 86–9. doi:10.1038/385086a0. PMIDΒ 8985253.
  26. ↑ 26.0 26.1 Blankenship JW, Varfolomeev E, Goncharov T, Fedorova AV, Kirkpatrick DS, Izrael-Tomasevic A, Phu L, Arnott D, Aghajan M, Zobel K, Bazan JF, Fairbrother WJ, Deshayes K, Vucic D (2009). “Ubiquitin binding modulates IAP antagonist-stimulated proteasomal degradation of c-IAP1 and c-IAP2(1)”. Biochem. J. 417 (1): 149–60. doi:10.1042/BJ20081885. PMIDΒ 18939944.
  27. ↑ Newton K, Matsumoto ML, Wertz IE, Kirkpatrick DS, Lill JR, Tan J, Dugger D, Gordon N, Sidhu SS, Fellouse FA, Komuves L, French DM, Ferrando RE, Lam C, Compaan D, Yu C, Bosanac I, Hymowitz SG, Kelley RF, Dixit VM (2008). “Ubiquitin chain editing revealed by polyubiquitin linkage-specific antibodies”. Cell. 134 (4): 668–78. doi:10.1016/j.cell.2008.07.039. PMIDΒ 18724939.
  28. ↑ Varfolomeev E, Goncharov T, Fedorova AV, Dynek JN, Zobel K, Deshayes K, Fairbrother WJ, Vucic D (2008). “c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation”. J. Biol. Chem. 283 (36): 24295–9. doi:10.1074/jbc.C800128200. PMCΒ 3259840. PMIDΒ 18621737.
  29. ↑ Liou ML, Liou HC (1999). “The ubiquitin-homology protein, DAP-1, associates with tumor necrosis factor receptor (p60) death domain and induces apoptosis”. J. Biol. Chem. 274 (15): 10145–53. doi:10.1074/jbc.274.15.10145. PMIDΒ 10187798.
  30. ↑ Okura T, Gong L, Kamitani T, Wada T, Okura I, Wei CF, Chang HM, Yeh ET (1996). “Protection against Fas/APO-1- and tumor necrosis factor-mediated cell death by a novel protein, sentrin”. J. Immunol. 157 (10): 4277–81. PMIDΒ 8906799.
  31. ↑ 31.0 31.1 Shu HB, Takeuchi M, Goeddel DV (1996). “The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex”. Proc. Natl. Acad. Sci. U.S.A. 93 (24): 13973–8. doi:10.1073/pnas.93.24.13973. PMCΒ 19479. PMIDΒ 8943045.
  32. ↑ SchΓΌtze S, Machleidt T, Adam D, Schwandner R, Wiegmann K, Kruse ML, Heinrich M, Wickel M, KrΓΆnke M (1999). “Inhibition of receptor internalization by monodansylcadaverine selectively blocks p55 tumor necrosis factor receptor death domain signaling”. J. Biol. Chem. 274 (15): 10203–12. doi:10.1074/jbc.274.15.10203. PMIDΒ 10187805.
  33. ↑ Pan G, O’Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J, Dixit VM (1997). “The receptor for the cytotoxic ligand TRAIL”. Science. 276 (5309): 111–3. doi:10.1126/science.276.5309.111. PMIDΒ 9082980.
  34. ↑ Soond SM, Terry JL, Colbert JD, Riches DW (2003). “TRUSS, a novel tumor necrosis factor receptor 1 scaffolding protein that mediates activation of the transcription factor NF-kappaB”. Mol. Cell. Biol. 23 (22): 8334–44. doi:10.1128/MCB.23.22.8334-8344.2003. PMCΒ 262424. PMIDΒ 14585990.
  35. ↑ Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G (2004). “A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway”. Nat. Cell Biol. 6 (2): 97–105. doi:10.1038/ncb1086. PMIDΒ 14743216.
  36. ↑ Barnhart BC, Peter ME (2003). “The TNF receptor 1: a split personality complex”. Cell. 114 (2): 148–50. doi:10.1016/s0092-8674(03)00561-0. PMIDΒ 12887914.
  37. ↑ Saltzman A, Searfoss G, Marcireau C, Stone M, Ressner R, Munro R, Franks C, D’Alonzo J, Tocque B, Jaye M, Ivashchenko Y (1998). “hUBC9 associates with MEKK1 and type I TNF-alpha receptor and stimulates NFkappaB activity”. FEBS Lett. 425 (3): 431–5. doi:10.1016/S0014-5793(98)00287-7. PMIDΒ 9563508.
Further reading

Further reading

  • Rath PC, Aggarwal BB (2000). “TNF-induced signaling in apoptosis”. J. Clin. Immunol. 19 (6): 350–64. doi:10.1023/A:1020546615229. PMIDΒ 10634209.
  • Chen G, Goeddel DV (2002). “TNF-R1 signaling: a beautiful pathway”. Science. 296 (5573): 1634–5. doi:10.1126/science.1071924. PMIDΒ 12040173.
  • Kollias G, Kontoyiannis D (2003). “Role of TNF/TNFR in autoimmunity: specific TNF receptor blockade may be advantageous to anti-TNF treatments”. Cytokine Growth Factor Rev. 13 (4–5): 315–21. doi:10.1016/S1359-6101(02)00019-9. PMIDΒ 12220546.
  • DodΓ© C, Cuisset L, Delpech M, Grateau G (2003). “TNFRSF1A-associated periodic syndrome (TRAPS), Muckle-Wells syndrome (MWS) and renal amyloidosis”. J. Nephrol. 16 (3): 435–7. PMIDΒ 12832748.
  • Stojanov S, McDermott MF (2007). “The tumour necrosis factor receptor-associated periodic syndrome: current concepts”. Expert Reviews in Molecular Medicine. 7 (22): 1–18. doi:10.1017/S1462399405009749. PMIDΒ 16216134.
  • Rezaei N (2007). “TNF-receptor-associated periodic syndrome (TRAPS): an autosomal dominant multisystem disorder”. Clin. Rheumatol. 25 (6): 773–7. doi:10.1007/s10067-005-0198-6. PMIDΒ 16447098.
External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.