TNF受容体1型
表示
TNF受容体1型(1型TNF受容体、tumor necrosis factor receptor 1、TNFR1)、TNFRSF1A(tumor necrosis factor receptor superfamily, member 1A)またはCD120aはTNF-αを結合する膜受容体であり、普遍的に発現している[5][6][7]。
機能
[編集]TNFRSF1A遺伝子にコードされるTNFR1は、TNFR2などとともにTNF受容体スーパーファミリーを構成する。このタンパク質はTNF-αに対する主要な受容体の1つであり、転写因子NF-κBの活性化、アポトーシスの媒介、炎症の調節といった機能を果たす。抗アポトーシスタンパク質BAG4やアダプタータンパク質TRADD、TRAF2がこの受容体と相互作用することが示されており、これらは受容体によって媒介されるシグナル伝達を調節する役割を果たしている[8]。
臨床的意義
[編集]この受容体の細胞外ドメイン領域に生じた生殖細胞系列変異は、TNF受容体関連周期性症候群(TRAPS)と呼ばれる遺伝疾患との関連が示されている[9]。この疾患の機序には受容体のクリアランスの機能不全が関係していると考えられている。
TNFRSF1A遺伝子の変異は、多発性硬化症のリスクの増大と関連している[10]。
統合失調症や双極性障害の患者では血清中の可溶性TNFR1濃度が上昇しており[11]、高値はより重篤な精神症状と関連している[12]。また、血清中の高濃度は認知機能障害や認知症とも関連している[13][14]。
相互作用
[編集]TNFRSF1Aは次に挙げる因子と相互作用することが示されている。
出典
[編集]- ^ a b c GRCh38: Ensembl release 89: ENSG00000067182 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030341 - Ensembl, May 2017
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- ^ Mouse PubMed Reference:
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- ^ International Multiple Sclerosis Genetics Consortium (2011). “The genetic association of variants in CD6, TNFRSF1A and IRF8 to multiple sclerosis: a multicenter case-control study”. PLOS ONE 6 (4): e18813. Bibcode: 2011PLoSO...618813.. doi:10.1371/journal.pone.0018813. PMC 3084233. PMID 21552549 .
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- ^ “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. (April 2013). doi:10.1016/j.schres.2012.12.023. PMID 23403415.
- ^ “Soluble TNF receptors are associated with Aβ metabolism and conversion to dementia in subjects with mild cognitive impairment”. Neurobiol. Aging 31 (11): 1877–84. (November 2010). doi:10.1016/j.neurobiolaging.2008.10.012. PMID 19070941.
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- ^ “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. (2002). PMID 11801527.
- ^ “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. (1997). doi:10.1074/jbc.272.9.5861. PMID 9038203.
- ^ “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. (1995). doi:10.1016/0014-5793(95)00534-G. PMID 7601280.
- ^ “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. (1997). doi:10.4049/jimmunol.158.9.4252. PMID 9126987.
- ^ a b c “TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex”. Immunity 4 (4): 387–96. (1996). doi:10.1016/S1074-7613(00)80252-6. PMID 8612133.
- ^ “Activation of death-inducing signaling complex (DISC) by pro-apoptotic C-terminal fragment of RIP”. Oncogene 19 (39): 4491–9. (2000). doi:10.1038/sj.onc.1203796. PMID 11002422.
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- ^ “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. (2003). doi:10.1128/MCB.23.22.8334-8344.2003. PMC 262424. PMID 14585990 .
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- ^ “hUBC9 associates with MEKK1 and type I TNF-alpha receptor and stimulates NFkappaB activity”. FEBS Lett. 425 (3): 431–5. (1998). doi:10.1016/S0014-5793(98)00287-7. PMID 9563508.
関連文献
[編集]- “TNF-induced signaling in apoptosis”. J. Clin. Immunol. 19 (6): 350–64. (2000). doi:10.1023/A:1020546615229. PMID 10634209.
- “TNF-R1 signaling: a beautiful pathway”. Science 296 (5573): 1634–5. (2002). Bibcode: 2002Sci...296.1634C. doi:10.1126/science.1071924. PMID 12040173.
- “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. (2003). doi:10.1016/S1359-6101(02)00019-9. PMID 12220546.
- “TNFRSF1A-associated periodic syndrome (TRAPS), Muckle–Wells syndrome (MWS) and renal amyloidosis”. J. Nephrol. 16 (3): 435–7. (2003). PMID 12832748.
- “The tumour necrosis factor receptor-associated periodic syndrome: current concepts”. Expert Reviews in Molecular Medicine 7 (22): 1–18. (2007). doi:10.1017/S1462399405009749. PMID 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. PMID 16447098.
関連項目
[編集]外部リンク
[編集]- TNFRSF1A protein, human - MeSH・アメリカ国立医学図書館・生命科学用語シソーラス
- Overview of all the structural information available in the PDB for UniProt: P19438 (Tumor necrosis factor receptor superfamily member 1A) at the PDBe-KB.