Tumor necrosis factor receptor 2 (TNFR2), also known astumor necrosis factor receptor superfamily member 1B (TNFRSF1B) andCD120b, is one of two membrane receptors that bindstumor necrosis factor-alpha (TNFα).[5][6] Like its counterpart,tumor necrosis factor receptor 1 (TNFR1), the extracellular region of TNFR2 consists of four cysteine-rich domains which allow for binding toTNFα.[7][8] TNFR1 and TNFR2 possess different functions when bound to TNFα due to differences in their intracellular structures, such as TNFR2 lacking a death domain (DD).[7]
The protein encoded by this gene is a member of thetumor necrosis factor receptor superfamily, which also containsTNFRSF1A. This protein andTNF-receptor 1 form a heterocomplex that mediates the recruitment of two anti-apoptotic proteins,c-IAP1 andc-IAP2, which possessE3 ubiquitin ligase activity. The function of IAPs in TNF-receptor signalling is unknown, however, c-IAP1 is thought to potentiate TNF-inducedapoptosis by theubiquitination and degradation of TNF-receptor-associated factor 2 (TRAF2), which mediates anti-apoptotic signals.Knockout studies in mice also suggest a role of this protein in protecting neurons from apoptosis by stimulating antioxidative pathways.[9]
Targeting of TNRF2 in tumor cells is associated with increased tumor cell death and decreased progression of tumor cell growth.[8]
Increased expression of TNFR2 is found inbreast cancer,cervical cancer,colon cancer, andrenal cancer.[8] A link between the expression of TNRF2 in tumor cells andlate-stage cancer has been discovered.[8] TNFR2 plays a significant role in tumor cell growth as it has been found that the loss of TNFR2 expression is linked with increased death of associated tumor cells and a significant standstill of further growth.[8] There is therapeutic potential in the targeting of TNFR2 for cancer treatments through TNFR2 inhibition.[12]
A small scale study of 289 Japanese patients suggested a minor increased predisposition from an amino acid substitution of the 196 allele at exon 6. Genomic testing of 81SLE patients and 207 healthy patients in a Japanese study showed 37% of SLE patients had a polymorphism on position 196 ofexon 6 compared to 18.8% of healthy patients. The TNFR2 196R allele polymorphism suggests that even one 196Rallele results in increased risk for SLE.[13]
^Komata T, Tsuchiya N, Matsushita M, Hagiwara K, Tokunaga K (June 1999). "Association of tumor necrosis factor receptor 2 (TNFR2) polymorphism with susceptibility to systemic lupus erythematosus".Tissue Antigens.53 (6):527–533.doi:10.1034/j.1399-0039.1999.530602.x.PMID10395102.
^Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, et al. (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway".Nature Cell Biology.6 (2):97–105.doi:10.1038/ncb1086.PMID14743216.S2CID11683986.{{cite journal}}: CS1 maint: overridden setting (link)
^Carpentier I, Coornaert B, Beyaert R (October 2008). "Smurf2 is a TRAF2 binding protein that triggers TNF-R2 ubiquitination and TNF-R2-induced JNK activation".Biochemical and Biophysical Research Communications.374 (4):752–757.doi:10.1016/j.bbrc.2008.07.103.PMID18671942.
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 Reviews.13 (4–5):315–321.doi:10.1016/S1359-6101(02)00019-9.PMID12220546.
Holtmann MH, Schuchmann M, Zeller G, Galle PR, Neurath MF (2003). "The emerging distinct role of TNF-receptor 2 (p80) signaling in chronic inflammatory disorders".Archivum Immunologiae et Therapiae Experimentalis.50 (4):279–288.PMID12371624.
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