Tumor necrosis factor receptor 1 explained

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 (TNFα).^{[1] [2] [3]}

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-κB, 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

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 are 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 are also associated with cognitive impairment and dementia.^{[9] [10]}

Interactions

TNFRSF1A has been shown to interact with:

• BAG4,^{[11] [12]}
• CASP10,^[13]
• FADD,^{[14] [15]}
• IKK2,^{[16] [17]}
• JAK1,^[18]
• JAK2,^[19]
• PIP4K2B,^[20]
• PSMD2,^{[21] [22]}
• RIPK1,^{[23] [24] [25] [26] [27]}
• SUMO1,^{[28] [29]}
• TRADD^{[11] [15] [25] [30] [31]}
• TRAF2,^{[15] [32] [33]}
• TRPC4AP,^[34]
• TNF,^{[35] [36]} and
• UBE2I.^[37]

See also

• Cluster of differentiation
• TNF receptor associated periodic syndrome

Further reading

• Rath PC, Aggarwal BB . TNF-induced signaling in apoptosis . Journal of Clinical Immunology . 19 . 6 . 350–364 . November 1999 . 10634209 . 10.1023/A:1020546615229 . 23194856 . free .
• Chen G, Goeddel DV . TNF-R1 signaling: a beautiful pathway . Science . 296 . 5573 . 1634–1635 . May 2002 . 12040173 . 10.1126/science.1071924 . 25321662 . 2002Sci...296.1634C .
• Kollias G, Kontoyiannis D . Role of TNF/TNFR in autoimmunity: specific TNF receptor blockade may be advantageous to anti-TNF treatments . Cytokine & Growth Factor Reviews . 13 . 4–5 . 315–321 . 2003 . 12220546 . 10.1016/S1359-6101(02)00019-9 . Dimitrios Kontoyiannis .
• Dodé C, Cuisset L, Delpech M, Grateau G . TNFRSF1A-associated periodic syndrome (TRAPS), Muckle-Wells syndrome (MWS) and renal amyloidosis . Journal of Nephrology . 16 . 3 . 435–437 . 2003 . 12832748 .
• Stojanov S, McDermott MF . The tumour necrosis factor receptor-associated periodic syndrome: current concepts . Expert Reviews in Molecular Medicine . 7 . 22 . 1–18 . October 2005 . 16216134 . 10.1017/S1462399405009749 . 35803989 .
• Rezaei N . TNF-receptor-associated periodic syndrome (TRAPS): an autosomal dominant multisystem disorder . Clinical Rheumatology . 25 . 6 . 773–777 . November 2006 . 16447098 . 10.1007/s10067-005-0198-6 . 41808394 .

Notes and References

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3. Book: Offermanns S, Rosenthal W . Encyclopedia of Molecular Pharmacology . 1 . 2008. Springer. Heidelberg, Germany. 1248. 2nd. 9783540389163.
4. Web site: Entrez Gene: TNFRSF1A tumor necrosis factor receptor superfamily, member 1A.
5. Kümpfel T, Hohlfeld R . Multiple sclerosis. TNFRSF1A, TRAPS and multiple sclerosis . Nature Reviews. Neurology . 5 . 10 . 528–529 . October 2009 . 19794511 . 10.1038/nrneurol.2009.154 . 40665495 .
6. The genetic association of variants in CD6, TNFRSF1A and IRF8 to multiple sclerosis: a multicenter case-control study . PLOS ONE . 6 . 4 . e18813 . April 2011 . 21552549 . 3084233 . 10.1371/journal.pone.0018813 . free . 2011PLoSO...618813. . International Multiple Sclerosis Genetics Consortium .
7. Hope S, Melle I, Aukrust P, Steen NE, Birkenaes AB, Lorentzen S, Agartz I, Ueland T, Andreassen OA . Similar immune profile in bipolar disorder and schizophrenia: selective increase in soluble tumor necrosis factor receptor I and von Willebrand factor . Bipolar Disorders . 11 . 7 . 726–734 . November 2009 . 19839997 . 10.1111/j.1399-5618.2009.00757.x . free . 10852/34620 .
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