TRAIL

Tumor necrosis factor superfamily member 10
250px PDB rendering based on 1d0g.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1D0G, 1D2Q, 1D4V, 1DG6, 1DU3, 4N90
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 exosome Biological process • apoptotic process • activation of cysteine-type endopeptidase activity involved in apoptotic process • immune response • signal transduction • cell surface receptor signaling pathway • cell-cell signaling • regulation of necrotic cell death • programmed cell death • positive regulation of apoptotic process • positive regulation of I-kappaB kinase/NF-kappaB signaling • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process • necroptotic process • positive regulation of release of cytochrome c from mitochondria • extrinsic apoptotic signaling pathway • activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway • programmed necrotic cell death • regulation of extrinsic apoptotic signaling pathway via death domain receptors • positive regulation of extrinsic apoptotic signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
File:PBB GE TNFSF10 202688 at tn.png
File:PBB GE TNFSF10 202687 s at tn.png
File:PBB GE TNFSF10 214329 x at tn.png
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8743	22035
Ensembl	ENSG00000121858	ENSMUSG00000039304
UniProt	P50591	P50592
RefSeq (mRNA)	NM_001190942	NM_009425
RefSeq (protein)	NP_001177871	NP_033451
Location (UCSC)	Chr 3: 172.51 – 172.52 Mb	Chr 3: 27.32 – 27.34 Mb
PubMed search	[1]	[2]

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.

TRAIL is a cytokine that is produced and secreted by most normal tissue cells. It causes apoptosis primarily in tumor cells, 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.

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

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. 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.

See also

• The Proteolysis Map

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)