TRAIL

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Tumor necrosis factor superfamily member 10
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PDB rendering based on 1d0g.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols TNFSF10 ; APO2L; Apo-2L; CD253; TL2; TRAIL
External IDs OMIM603598 MGI107414 HomoloGene2824 ChEMBL: 5813 GeneCards: TNFSF10 Gene
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.[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]

See also

References

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Further reading

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External links