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Tumor necrosis factor (ligand) superfamily, member 10

PDB rendering based on 1d0g.
Available structures
1d0g, 1d2q, 1d4v, 1dg6, 1du3
Identifiers
Symbols TNFSF10; APO2L; Apo-2L; CD253; TL2; TRAIL
External IDs OMIM603598 MGI107414 HomoloGene2824 GeneCards: TNFSF10 Gene
RNA expression pattern
PBB GE TNFSF10 202688 at tn.png
PBB GE TNFSF10 202687 s at tn.png
PBB GE TNFSF10 214329 x at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 8743 22035
Ensembl ENSG00000121858 ENSMUSG00000039304
UniProt P50591 Q3TZR6
RefSeq (mRNA) NM_003810 NM_009425
RefSeq (protein) NP_003801 NP_033451
Location (UCSC) Chr 3:
173.71 - 173.72 Mb
Chr 3:
27.51 - 27.53 Mb
PubMed search [1] [2]

In the field of cell biology, TNF-related apoptosis-inducing ligand (TRAIL), is a protein which functions as a ligand which induces the process of cell death called apoptosis. TRAIL has also been designated CD253 (cluster of differentiation 253).[1][2]

Contents

Gene

In humans, the gene that encodes for 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.[3] 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.[4][5][6]

See also

References

  1. ^ 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.  
  2. ^ 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. http://www.jbc.org/cgi/content/full/271/22/12687.  
  3. ^ 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. PMID 18276109.  
  4. ^ Kaptein, A; Jansen M, Dilaver G, Kitson J, Dash L, Wang E, Owen M J, Bodmer J L, Tschopp J, Farrow S N (Nov. 2000). "Studies on the interaction between TWEAK and the death receptor WSL-1/TRAMP (DR3)". FEBS Lett. (NETHERLANDS) 485 (2-3): 135–41. doi:10.1016/S0014-5793(00)02219-5. ISSN 0014-5793. PMID 11094155.  
  5. ^ Walczak, H; Degli-Esposti M A, Johnson R S, Smolak P J, Waugh J Y, Boiani N, Timour M S, Gerhart M J, Schooley K A, Smith C A, Goodwin R G, Rauch C T (Sep. 1997). "TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL". EMBO J. (ENGLAND) 16 (17): 5386–97. doi:10.1093/emboj/16.17.5386. ISSN 0261-4189. PMID 9311998.  
  6. ^ Hymowitz, S G; Christinger H W, Fuh G, Ultsch M, O'Connell M, Kelley R F, Ashkenazi A, de Vos A M (Oct. 1999). "Triggering cell death: the crystal structure of Apo2L/TRAIL in a complex with death receptor 5". Mol. Cell (UNITED STATES) 4 (4): 563–71. doi:10.1016/S1097-2765(00)80207-5. ISSN 1097-2765. PMID 10549288.  

Further reading

  • Wiley S, Schooley K, Smolak P, Din W, Huang C, Nicholl J, Sutherland G, Smith T, Rauch C, Smith C (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.  
  • Almasan A, Ashkenazi A (2004). "Apo2L/TRAIL: apoptosis signaling, biology, and potential for cancer therapy.". Cytokine Growth Factor Rev. 14 (3-4): 337–48. doi:10.1016/S1359-6101(03)00029-7. PMID 12787570.  
  • Cha SS, Song YL, Oh BH (2004). "Specificity of molecular recognition learned from the crystal structures of TRAIL and the TRAIL:sDR5 complex.". Vitam. Horm. 67: 1–17. doi:10.1016/S0083-6729(04)67001-4. PMID 15110168.  
  • Song C, Jin B (2005). "TRAIL (CD253), a new member of the TNF superfamily.". J. Biol. Regul. Homeost. Agents 19 (1-2): 73–7. PMID 16178278.  
  • Bucur O, Ray S, Bucur MC, Almasan A (2006). "APO2 ligand/tumor necrosis factor-related apoptosis-inducing ligand in prostate cancer therapy.". Front. Biosci. 11: 1549–68. doi:10.2741/1903. PMID 16368536.  

External links

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Simple English

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A trail is a pedestrian path or road mainly used for walking, but often also for cycling, cross-country skiing or other activities. Some trails are off-limits to everyone other than hikers, and few trails allow motorized vehicles.

Contents

Nomenclature

In the United States, the word footpath is also used to mean a trail; however in Australian English, New Zealand English, Indian English, and Irish English this word means "sidewalk" (American English) or "pavement" (British English).

In Australia, the word track can be used interchangeably with trail, and can refer to anything from a dirt road to a pedestrian walkway (generally also unpaved). The term "trail" gained popularity during World War II, when many servicemen from the United States were stationed in Australia, which probably influenced its being adopted by elements of the Australian media at the time (see Kokoda Track). In New Zealand, the word track is used almost exclusively except in reference to cross-country skiing, where trail is used.

Trail types and use

Walking trails

in Panamá]]

Trail use has become very popular for a wide variety of users. Some trails are meant as nature trails, and are used by people learning about the natural world. Many trails are day trails, what means that they are generally used by people out for a short hike, less than a day. Some trails are backpacking trails, or long-distance trails, and are used by both day hikers and by backpackers. Some of the trails are over a thousand miles (1,500 km) long and may be hiked in sections by backpackers, or completed in one trip by dedicated hikers. Some trails are specifically used by other outdoor enthusiasts to gain access to another feature, such as good climbing sites. Many runners also favor running on trails rather than pavement, as giving a more vigorous work-out and better developing agility skills, as well as providing a more pleasant exercise environment. See trail running.

Stairway Trails

Stairway is another way to ascend higher slopes. Stairway trails are usually for walking only. The stairs are constructed using cuts in dirt, rocks or concrete. Popular stair way trails include Stairway Trails in Bernal Heights East - San Francisco, Stairs at many hill top Hindu temple (Tirumala, Palani) used during Pilgrimage & Machu Picchu.

Bicycle trails

Recent decades have seen an explosion of interest in cycling, both street-type and off-road type. A common term for these facilities is simply "bike trail". These trails may be built to a different set of standards than foot trails, requiring more stable, harder surfaces, less strenuous grades, longer sight visibility, and less sharp changes in direction. On the other hand, the cross-slope of a bike trail may be significantly greater than a foot trail, and the actual treadway may be narrower in some cases.

Equestrian trails

Horseback riding has continued to be a popular activity for many trail users. Again, horse trails must be built to different standards than other trails. Sight distance is an important issue with horse trails, as is overhead and side clearance. While trail surface types are a relatively unimportant issue with hikers, they may be an important issue with horses.

Cross-country skiing

In cross-country skiing, a trail (also called a 'track' or 'piste') refers to the parallel grooves cut into the snow, one for each ski.

Motorized trails

Motorized trail use also remains very popular with some people. Such terms as ORV, four-wheeling, all-terrain vehicle, and others actually have highly specific meanings.

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