TRAIL

Source: Wikipedia, the free encyclopedia.
(Redirected from
TNF-related apoptosis-inducing ligand
)
This article is about the protein in cell biology. For other uses, see Trail (disambiguation).
TNFSF10
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl

ENSG00000121858

ENSMUSG00000039304

UniProt

P50591

P50592

RefSeq (mRNA)

NM_001190942
NM_001190943
NM_003810

NM_009425

RefSeq (protein)

NP_001177871
NP_001177872
NP_003801

NP_033451

Location (UCSC)Chr 3: 172.51 – 172.52 MbChr 3: 27.37 – 27.4 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5][6]

TRAIL is a

death receptors. TRAIL and its receptors have been used as the targets of several anti-cancer therapeutics since the mid-1990s, such as Mapatumumab. However, as of 2013, these have not shown significant survival benefit.[8] TRAIL has also been implicated as a pathogenic or protective factor in various pulmonary diseases, particularly pulmonary arterial hypertension.[9]

TRAIL has also been designated CD253 (cluster of differentiation 253) and TNFSF10 (tumor necrosis factor (ligand) superfamily, member 10).[7]

Gene

In humans, the gene that encodes TRAIL is located at chromosome 3q26, which is not close to other TNF family members.[5] 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

OCT-1, AP3, PEA3, CF-1, and ISRE.[citation needed
]

The TRAIL gene as a drug target

TIC10 (which causes expression of TRAIL) was investigated in mice with various tumour types.[8]

ONC201 causes expression of TRAIL which kills some cancer cells.[10]

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
. 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

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. Application of engineered ligands that have variable affinity for different death (DR4 and DR5) and decoy receptors (DCR1 and DCR2) may allow selective targeting of cancer cells by controlling activation of Type 1/Type 2 pathways of cell death and single cell fluctuations. Luminescent iridium complex-peptide hybrids, which mimic TRAIL, have recently been synthesized in vitro. These artificial TRAIL mimics bind to DR4/DR5 on cancer cells and induce cell death via both apoptosis and necrosis, which makes them a potential candidate for anticancer drug development.[12][13]

The TRAIL receptors as a drug target

In clinical trials only a small proportion of cancer patients responded to various drugs that targeted TRAIL death receptors. Many cancer cell lines develop resistance to TRAIL and limits the efficacy of TRAIL-based therapies.[14]

Interactions

TRAIL has been shown to

TNFRSF10B.[15][16][17]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000121858 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000039304 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^
    PMID 8777713
    .
  6. PMID 8663110
    .
  7. ^ a b "TNFSF10". NCBI Gene.
  8. ^
    S2CID 76236123
    .
  9. PMID 30101145
    .
  10. ^ ONC201: Stressing tumors to death. Feb 2016
  11. PMID 18276109
    .
  12. S2CID 52149418
    .
  13. PMID 30154833
    .
  14. PMID 22580613
    .
  15. S2CID 38403545
    .
  16. PMID 9311998
    .
  17. PMID 10549288
    .

Further reading

External links
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