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have or establish a relationship to; "She relates well to her peers"
be in a relationship with; "How are these two observations related?" (同)interrelate
give an account of; "The witness related the events"
connected by kinship, common origin, or marriage
being connected either logically or causally or by shared characteristics ; "painting and the related arts"; "school-related activities"; "related to micelle formation is the...ability of detergent actives to congregate at oil-water interfaces" (同)related to
a type of cell death in which the cell uses specialized cellular machinery to kill itself; a cell suicide mechanism that enables metazoans to control cell number and eliminate cells that threaten the animals survival (同)programmed_cell_death, caspase-mediated cell death
the 20th letter of the Roman alphabet (同)t
a substance (an atom or molecule or radical or ion) that forms a complex around a central atom

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/05/19 23:25:13」(JST)

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In the field of cell biology, TNF-related apoptosis-inducing ligand (TRAIL), is a protein functioning as a ligand that induces the process of cell death called apoptosis.^[1]^[2]

TRAIL is a cytokine that is produced and secreted by most normal tissue cells. It causes apoptosis primarily in tumor cells,^[3] by binding to certain death receptors. It has been used as a target of several anti-cancer therapeutics since the mid-1990s. These however have not shown significant survival benefit.^[4]

TRAIL has also been designated CD253 (cluster of differentiation 253) and TNFSF10 (tumor necrosis factor (ligand) superfamily, member 10).^[3]

Gene

In humans, the gene that encodes TRAIL is located at chromosome 3q26, which is not close to other TNF family members. The genomic structure of the TRAIL gene spans approximately 20 kb and is composed of five exonic segments 222, 138, 42, 106, and 1245 nucleotides and four introns of approximately 8.2, 3.2, 2.3 and 2.3 kb. The TRAIL gene lacks TATA and CAAT boxes and the promotor region contains putative response elements for GATA, AP-1, C/EBP, SP-1, OCT-1, AP3, PEA3, CF-1, and ISRE.

Structure

TRAIL shows homology to other members of the tumor necrosis factor superfamily. It is composed of 281 amino acids and has characteristics of a type II transmembrane protein (i.e. no leader sequence and an internal transmembrane domain). The N-terminal cytoplasmic domain is not conserved across family members, however, the C-terminal extracellular domain is conserved and can be proteolytically cleaved from the cell surface. TRAIL forms a homotrimer that binds three receptor molecules.

Function

TRAIL binds to the death receptors DR4 (TRAIL-RI) and DR5 (TRAIL-RII). The process of apoptosis is caspase-8-dependent. Caspase-8 activates downstream effector caspases including procaspase-3, -6, and -7, leading to activation of specific kinases.^[5] TRAIL also binds the receptors DcR1 and DcR2, which do not contain a cytoplasmic domain (DcR1) or contain a truncated death domain (DcR2). DcR1 functions as a TRAIL-neutralizing decoy-receptor. The cytoplasmic domain of DcR2 is functional and activates NFkappaB. In cells expressing DcR2, TRAIL binding therefore activates NFkappaB, leading to transcription of genes known to antagonize the death signaling pathway and/or to promote inflammation.

Interactions

TRAIL has been shown to interact with TNFRSF10B.^[6]^[7]^[8]

References

^ Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA (December 1995). "Identification and characterization of a new member of the TNF family that induces apoptosis". Immunity 3 (6): 673–82. doi:10.1016/1074-7613(95)90057-8. PMID 8777713.
^ Pitti RM, Marsters SA, Ruppert S, Donahue CJ, Moore A, Ashkenazi A (May 1996). "Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family". J. Biol. Chem. 271 (22): 12687–90. doi:10.1074/jbc.271.22.12687. PMID 8663110.
^ ^a ^b "TNFSF10". NCBI Gene.
^ Cormier Z (February 2013). "Small-molecule drug drives cancer cells to suicide". Nature 494. doi:10.1038/nature.2013.12385.
^ Song JJ, Lee YJ (May 2008). "Differential cleavage of Mst1 by caspase-7/-3 is responsible for TRAIL-induced activation of the MAPK superfamily". Cell. Signal. 20 (5): 892–906. doi:10.1016/j.cellsig.2008.01.001. PMC 2483832. PMID 18276109.
^ Kaptein A, Jansen M, Dilaver G, Kitson J, Dash L, Wang E, Owen MJ, Bodmer JL, Tschopp J, Farrow SN (November 2000). "Studies on the interaction between TWEAK and the death receptor WSL-1/TRAMP (DR3)". FEBS Lett. 485 (2-3): 135–41. doi:10.1016/S0014-5793(00)02219-5. PMID 11094155.
^ Walczak H, Degli-Esposti MA, Johnson RS, Smolak PJ, Waugh JY, Boiani N, Timour MS, Gerhart MJ, Schooley KA, Smith CA, Goodwin RG, Rauch CT (September 1997). "TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL". EMBO J. 16 (17): 5386–97. doi:10.1093/emboj/16.17.5386. PMC 1170170. PMID 9311998.
^ Hymowitz SG, Christinger HW, Fuh G, Ultsch M, O'Connell M, Kelley RF, Ashkenazi A, de Vos AM (October 1999). "Triggering cell death: the crystal structure of Apo2L/TRAIL in a complex with death receptor 5". Mol. Cell 4 (4): 563–71. doi:10.1016/S1097-2765(00)80207-5. PMID 10549288.

External links

[3] Apoptosis, Trail & Caspase 8 - The Proteolysis Map-animation
PDB 1D2Q
TRAIL Protein at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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English Journal

Oxaliplatin regulates expression of stress ligands in ovarian cancer cells and modulates their susceptibility to natural killer cell-mediated cytotoxicity.

Siew YY1, Neo SY1, Yew HC1, Lim SW1, Ng YC1, Lew SM1, Seetoh WG1, Seow SV2, Koh HL3.
International immunology.Int Immunol.2015 Dec;27(12):621-32. doi: 10.1093/intimm/dxv041. Epub 2015 Jul 2.
Selected cytotoxic chemicals can provoke the immune system to recognize and destroy malignant tumors. Most of the studies on immunogenic cell death are focused on the signals that operate on a series of receptors expressed by dendritic cells to induce tumor antigen-specific T-cell responses. Here, w
PMID 26138671

Goniothalamin enhances TRAIL-induced apoptosis in colorectal cancer cells through DR5 upregulation and cFLIP downregulation.

Sophonnithiprasert T1, Nilwarangkoon S1, Nakamura Y2, Watanapokasin R1.
International journal of oncology.Int J Oncol.2015 Dec;47(6):2188-96. doi: 10.3892/ijo.2015.3204. Epub 2015 Oct 13.
The combination of TNF-related apoptosis-inducing ligand (TRAIL) and bioactive compound to enhance apoptosis in TRAIL-resistant cancer is one of cancer treatment strategies. TRAIL possesses the unique capacity to selectively induce apoptosis in cancer cells both in vitro and in vivo with little ef
PMID 26499766

S-nitrosylation in TNF superfamily signaling pathway: Implication in cancer.

Plenchette S1, Romagny S2, Laurens V2, Bettaieb A2.
Redox biology.Redox Biol.2015 Dec;6:507-15. doi: 10.1016/j.redox.2015.08.019. Epub 2015 Sep 8.
One of the key features of tumor cells is the acquisition of resistance to apoptosis. Thus, novel therapeutic strategies that circumvent apoptotic resistance and result in tumor elimination are needed. One strategy to induce apoptosis is to activate death receptor signaling pathways. In the tumor mi
PMID 26448396

Japanese Journal

Dysregulated Atrial Gene Expression of Osteoprotegerin/Receptor Activator of Nuclear Factor-κB (RANK)/RANK Ligand Axis in the Development and Progression of Atrial Fibrillation

CAO Hailong,WANG Jian,XI Lei,ROE Oluf Dimitri,CHEN Yijiang,WANG Dongjin
Circulation journal : official journal of the Japanese Circulation Society 75(12), 2781-2788, 2011-11-25
… Osteoprotegerin (OPG)/receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL) axis, a key regulatory system in bone homeostasis, was recently linked to some cardiovascular disorders for its regulatory functions to myocardial remodeling. …
NAID 10030033161

癌の「分子標的予防」 : その理論と可能性

酒井敏行
日本衞生學雜誌 66(1), 3-12, 2011-01-15
… We then investigated the TNF-related apoptosis-inducing ligand (TRAIL)-death receptor 5 (DR5) pathway as a candidate of the target, and found that many cancer-preventive food factors could enhance the pathway resulting in the synergistic apoptosis of various cancer cells. …
NAID 10029363493

Recent progress in the etiopathogenesis of pediatric biliary disease, particularly Caroli's disease with congenital hepatic fibrosis and biliary atresia

Nakanuma Yasuni,Harada Kenichi,Sato Yasunori,Ikeda Hiroko
Histology and Histopathology 25(2), 223-235, 2010-02
… Disordered cell kinetics, including apoptosis of biliary epithelial cells (BECs), may be significantly related to ductal plate malformation, and laminin and type IV collagen were immunohistochemically reduced in the basement membrane of intrahepatic bile ducts of ARPKD, and such a reduction is an additional factor for the dilatation of bile ducts. …
NAID 120004186264

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★リンクテーブル★

リンク元	「TNF関連アポトーシス誘導リガンド」「腫瘍壊死因子関連アポトーシス誘導リガンド」
拡張検索	「TNF-related apoptosis-inducing ligand receptor」
関連記事	「relate」「T」「TNF」

「TNF関連アポトーシス誘導リガンド」

Tumor necrosis factor (ligand) superfamily, member 10
	; PDB rendering based on 1d0g.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1D0G, 1D2Q, 1D4V, 1DG6, 1DU3
Identifiers
Symbols	TNFSF10 ; APO2L; Apo-2L; CD253; TL2; TRAIL
External IDs	OMIM: 603598 MGI: 107414 HomoloGene: 2824 ChEMBL: 5813 GeneCards: TNFSF10 Gene
Gene ontology
Molecular function	• receptor binding; • cytokine activity; • tumor necrosis factor receptor binding; • protein binding; • metal ion binding;
Cellular component	• extracellular region; • extracellular space; • integral component of plasma membrane; • extracellular vesicular exosome;
Biological process	• apoptotic process; • activation of cysteine-type endopeptidase activity involved in apoptotic process; • immune response; • signal transduction; • cell-cell signaling; • male gonad development; • response to insulin; • positive regulation of apoptotic process; • positive regulation of I-kappaB kinase/NF-kappaB signaling; • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; • positive regulation of release of cytochrome c from mitochondria; • apoptotic signaling pathway; • positive regulation of extrinsic apoptotic signaling pathway; • regulation of extrinsic apoptotic signaling pathway in absence of ligand;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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