Affinage

TNFSF10

Tumor necrosis factor ligand superfamily member 10 · UniProt P50591

Round 2 corrected
Length
281 aa
Mass
32.5 kDa
Annotated
2026-04-28
130 papers in source corpus 40 papers cited in narrative 40 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TNFSF10 (TRAIL/Apo2L) is a homotrimeric type II transmembrane cytokine of the TNF superfamily that induces apoptosis in transformed cells by engaging the death-domain-containing receptors DR4 (TRAIL-R1) and DR5 (TRAIL-R2), which recruit FADD and caspase-8 into a death-inducing signaling complex (DISC); full caspase-8 activation requires CUL3-mediated polyubiquitination and p62-dependent aggregation, and is modulated by post-translational modifications including O-glycosylation of DR4/DR5 ectodomains (promoting receptor clustering) and O-GlcNAcylation of DR4-Ser424 (PMID:8777713, PMID:10894160, PMID:19427028, PMID:17167167, PMID:30987996). Apoptotic signaling is negatively regulated by decoy receptors (TRAIL-R3, TRAIL-R4), the caspase-8 inhibitor FLIP, and TRAF2, while TRAIL-R4 additionally activates NF-κB (PMID:9242610, PMID:9430226, PMID:25299769). Beyond apoptosis, TRAIL signals non-apoptotically through ERK to regulate erythroid differentiation, through TAK1–AMPK to induce cytoprotective autophagy in normal epithelial cells, and through nuclear TRAIL-R2 trafficking to inhibit let-7 miRNA maturation (PMID:12969966, PMID:19197243, PMID:31416165). TRAIL gene expression is transcriptionally controlled by FOXO factors (via the PI3K–PTEN–Akt axis), NF-κB, interferon-response elements, and Sp1 (recruited upon HDAC inhibitor treatment), and is induced in astrocytes by IFNγ from meningeal NK cells to limit CNS inflammation via T cell apoptosis (PMID:12351634, PMID:15619633, PMID:18701496, PMID:33408417).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1995 High

    Identification of TRAIL as a TNF-family cytokine that induces apoptosis in transformed cells answered the question of whether the TNF superfamily contained additional death ligands with tumor-selective activity.

    Evidence cDNA cloning and recombinant soluble protein apoptosis assays across diverse tumor lines

    PMID:8663110 PMID:8777713

    Open questions at the time
    • Cognate receptor(s) unknown
    • Mechanism of tumor selectivity unexplained
    • In vivo physiological role not yet addressed
  2. 1997 High

    Rapid identification of four TRAIL receptors (DR4, DR5 with death domains; TRAIL-R3 and TRAIL-R4 as decoy/modulatory receptors) established a combinatorial receptor system governing differential cell sensitivity to TRAIL.

    Evidence Receptor cloning, binding affinity measurements, death domain functional assays, ectopic expression protection experiments, NF-κB reporter assays across multiple independent laboratories

    PMID:9082980 PMID:9242610 PMID:9311998 PMID:9314565 PMID:9325248 PMID:9373179 PMID:9430226

    Open questions at the time
    • Proximal signaling adaptors at the DISC not yet defined for TRAIL receptors
    • Relative contributions of DR4 vs DR5 in different tissues unknown
    • Whether DR4 uses FADD was disputed across early studies
  3. 1997 High

    Demonstration that FADD, TRADD, and FLIP regulate TRAIL receptor signaling, and that DR4 and DR5 can form heterocomplexes, established the proximal adaptor framework for TRAIL-induced death signaling.

    Evidence Co-immunoprecipitation of FADD/TRADD with TRAIL receptors, dominant-negative FADD and FLIP overexpression blocking apoptosis

    PMID:9430228

    Open questions at the time
    • Whether caspase-8 is recruited directly to the native DISC not yet shown
    • Stoichiometry of DISC components undefined
  4. 1999 High

    The crystal structure of the TRAIL trimer–DR5 ectodomain complex revealed the molecular basis of ligand–receptor interaction, showing three DR5 molecules bound in crevices between TRAIL monomers.

    Evidence X-ray crystallography of Apo2L/TRAIL–DR5 complex

    PMID:10549288

    Open questions at the time
    • No structure of full-length receptor or intracellular DISC assembly
    • Structural basis for decoy receptor competition not resolved
  5. 2000 High

    Native DISC immunoprecipitation combined with FADD- and caspase-8-deficient cells proved that both FADD and caspase-8 are essential and independently recruited components of the TRAIL DISC, resolving earlier conflicting data.

    Evidence Native DISC precipitation from ligand-stimulated cells; FADD-deficient and caspase-8-deficient Jurkat genetic knockouts

    PMID:10894160

    Open questions at the time
    • Post-translational regulation of caspase-8 at the DISC unknown
    • Role of caspase-10 not yet clarified
  6. 2002 High

    Multiple discoveries established transcriptional control of TRAIL: FOXO factors bind the TRAIL promoter (linking PI3K–PTEN–Akt to TRAIL expression), NF-κB and interferon-response elements also regulate transcription, and caspase-10 was shown to be recruited to the DISC in a FADD-dependent but caspase-8-non-redundant manner.

    Evidence Promoter reporter mapping (FKHRL1-responsive element at −138 to −121), adenoviral FOXO overexpression, caspase-10 native DISC immunoprecipitation and overexpression rescue in caspase-8-null cells

    PMID:12198154 PMID:12351634

    Open questions at the time
    • Additional transcription factors and chromatin regulators not yet identified
    • Physiological role of caspase-10 in TRAIL signaling unclear
  7. 2003 High

    TRAIL was found to have non-apoptotic functions: ERK-dependent regulation of erythroid differentiation via TRAIL-R2, and differentiation induction (not apoptosis) in intestinal epithelial cells, expanding TRAIL biology beyond cell death.

    Evidence Pharmacological ERK/p38/JNK inhibitors in primary CD34+ erythroid cells; Fc-TRAIL-R2 chimera blocking in intestinal epithelial cells

    PMID:12969966 PMID:16245299

    Open questions at the time
    • Downstream transcriptional targets of ERK in erythroid TRAIL signaling unknown
    • Mechanism linking TRAIL-R2 to p21/p27 induction in gut epithelium not defined
  8. 2004 High

    HDAC inhibitors were shown to directly activate the TNFSF10 promoter in AML cells, and FLIP was confirmed as a potent DISC-level inhibitor of caspase-8 activation, establishing two pharmacologically actionable nodes in the pathway.

    Evidence Promoter reporter assays with HDAC inhibitors, RNAi dissection of TRAIL/p21/differentiation, FLIP overexpression and knockdown with caspase-8 processing readouts

    PMID:15110178 PMID:15619633

    Open questions at the time
    • Identity of the HDAC(s) that repress TRAIL transcription unknown
    • Whether FLIP regulation differs between TRAIL-R1 and TRAIL-R2 DISCs not addressed
  9. 2007 High

    O-glycosylation of DR4/DR5 ectodomains by GALNT14 was identified as a determinant of TRAIL sensitivity, promoting ligand-induced receptor clustering and caspase-8 activation—answering why cells with equivalent receptor levels differ in TRAIL responsiveness.

    Evidence GALNT14 RNAi/overexpression, mass spectrometry glycan mapping of DR5, progressive mutagenesis of O-glycosylation sites, receptor clustering assays

    PMID:17167167

    Open questions at the time
    • Full set of glycosyltransferases modifying DR4/DR5 not catalogued
    • Structural mechanism by which O-glycans promote clustering unknown
  10. 2009 High

    Two key post-translational mechanisms were uncovered: CUL3-mediated polyubiquitination of caspase-8 (reversed by A20, read by p62) drives caspase-8 aggregation for full activation; and TRAIL-induced TAK1–AMPK signaling triggers cytoprotective autophagy in normal cells, explaining their TRAIL resistance.

    Evidence CUL3/RBX1/A20/p62 RNAi with DISC IP and caspase processing assays; TAK1/LKB1/CaMKKβ RNAi with AMPK/mTORC1 epistasis in normal vs. transformed cells

    PMID:19197243 PMID:19427028

    Open questions at the time
    • Specific CUL3 substrate adaptor for caspase-8 not identified
    • Whether p62-mediated aggregation occurs in all TRAIL-sensitive cell types unknown
    • How TAK1 is activated by TRAIL receptors not mechanistically resolved
  11. 2014 High

    TRAF2 was established as a negative regulator of both TRAIL-induced apoptosis and necroptosis, and nuclear TRAIL-R2 was shown to inhibit let-7 miRNA maturation via the Microprocessor complex, revealing a non-canonical nuclear signaling function.

    Evidence TRAF2 siRNA with RIP3 reconstitution and necrostatin-1; TRAIL-R2 NES mutagenesis, CRM-1 inhibition, co-IP with Microprocessor components, let-7 processing assays

    PMID:25165876 PMID:25299769

    Open questions at the time
    • Mechanism of TRAF2 recruitment to the TRAIL DISC not defined
    • Nuclear TRAIL-R2 findings based on limited cell types; generalizability unclear
    • Physiological significance of let-7 regulation by TRAIL-R2 in vivo not established
  12. 2019 High

    O-GlcNAcylation of DR4-Ser424 was identified as essential for DISC and necrosome formation, discriminating DR4 from DR5 signaling and linking metabolic status (glucose levels) to TRAIL sensitivity.

    Evidence OGT knockdown, DR4-S424 site-directed mutagenesis, DISC/necrosome co-IP, receptor clustering assays, cancer patient mutation screen, glucose modulation

    PMID:30987996

    Open questions at the time
    • Whether other death domain residues are O-GlcNAcylated not surveyed
    • In vivo validation of glucose-dependent TRAIL sensitization lacking
  13. 2021 High

    TRAIL expression in LAMP1+ astrocytes, driven by IFNγ from meningeal NK cells and modulated by the gut microbiome, was shown to limit CNS inflammation by inducing T cell apoptosis—establishing a physiological immune-regulatory role for TRAIL in vivo.

    Evidence CRISPR-Cas9 in vivo perturbation of astrocytic TRAIL, scRNA-seq, germ-free mouse models, TRAIL-DR5 blocking

    PMID:33408417

    Open questions at the time
    • Whether astrocytic TRAIL has non-apoptotic signaling effects on T cells unknown
    • Specific gut microbial taxa driving meningeal NK IFNγ not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the CUL3 substrate adaptor that ubiquitinates caspase-8, the structural basis of TRAIL-induced receptor clustering, the full spectrum of non-apoptotic TRAIL signaling outputs in different tissues, and the in vivo relevance of nuclear TRAIL-R2 in let-7 regulation.
  • CUL3 substrate adaptor for caspase-8 ubiquitination unidentified
  • No full-length TRAIL receptor structure with intracellular domain
  • Tissue-specific balance between apoptotic and non-apoptotic TRAIL signaling not systematically mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0090729 toxin activity 3
Localization
GO:0005576 extracellular region 3 GO:0005886 plasma membrane 3
Pathway
R-HSA-5357801 Programmed Cell Death 6 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 3 R-HSA-9612973 Autophagy 3
Partners
CASP8CFLARFADDTNFRSF10ATNFRSF10BTNFRSF10CTNFRSF10DTRAF2

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 TRAIL (TNFSF10) was identified as a novel type II transmembrane protein of the TNF family, with its C-terminal extracellular domain forming a homotrimeric structure. Both full-length cell-surface TRAIL and picomolar concentrations of soluble TRAIL rapidly induce apoptosis in a wide variety of transformed cell lines. The TRAIL gene is located on chromosome 3q26. cDNA cloning, transfection/overexpression, apoptosis assays with recombinant soluble protein Immunity High 8777713
1996 Apo-2L (TRAIL/TNFSF10) is a 281-amino acid type II transmembrane protein whose C-terminal extracellular region forms a homotrimeric subunit structure. Soluble Apo-2L induces apoptosis in lymphoid and non-lymphoid tumor cell lines through a receptor distinct from Fas/Apo-1 and TNF receptors, as soluble Fas and TNF receptors do not inhibit its activity. Recombinant protein expression, apoptosis assays, receptor competition experiments The Journal of biological chemistry High 8663110
1997 DR4 (TRAIL-R1), identified as the first receptor for TRAIL, is a member of the TNF-receptor family containing a cytoplasmic death domain capable of engaging the apoptotic machinery. DR4 could not use FADD to transmit the death signal (unlike Fas, TNFR-1, and DR3), suggesting use of distinct proximal signaling machinery. DR4 did not activate NF-κB in the system studied. Receptor cloning, death domain functional assays, FADD interaction studies, NF-κB reporter assays Science High 9082980
1997 TRAIL-R2 (DR5) was identified as a distinct receptor for TRAIL via ligand-based affinity purification from human cell lines. TRAIL-R2 contains two extracellular cysteine-rich repeats and a cytoplasmic death domain. Unlike TRAIL-R1, TRAIL-R2 mediates apoptosis via the intracellular adaptor molecule FADD/MORT1. The TRAIL-R2 gene maps to chromosome 8p22-21. Ligand-based affinity purification, molecular cloning, FADD interaction assays, Fc fusion protein blocking experiments The EMBO journal High 9311998
1997 TRID (TRAIL-R3/DcR1), an antagonist decoy receptor for TRAIL, was identified with an extracellular TRAIL-binding domain and transmembrane domain but no intracellular signaling domain. Ectopic expression of TRID protected cells from TRAIL-induced apoptosis. A second death domain-containing receptor DR5 preferentially engaged a FLICE (caspase-8)-related death protease. Gene cloning, ectopic expression, apoptosis protection assays Science High 9242610
1997 TRAIL-R2 (DR5) and TRAIL-R3 were characterized: TRAIL-R2 is structurally similar to TRAIL-R1 and capable of inducing apoptosis; TRAIL-R3 does not promote cell death, is highly glycosylated, and is membrane-bound via a GPI anchor. TRAIL-R3 has TAPE repeats extending its structure. All three receptors bind TRAIL with similar affinity. Receptor cloning, apoptosis assays, binding affinity measurements, glycosylation and GPI anchor characterization FEBS letters High 9373179
1997 TRAIL-R4, a fourth TRAIL receptor, was cloned and characterized. TRAIL-R4 retains an incomplete death domain (one-third of consensus motif) and activates NF-κB similarly to TRAIL-R1/R2, but cannot induce apoptosis. Transient overexpression of TRAIL-R4 in TRAIL-sensitive cells conferred complete protection from TRAIL-mediated killing. TRAIL-R4 gene maps to chromosome 8p22-21, clustered with other TRAIL receptor genes. Gene cloning, NF-κB reporter assays, apoptosis assays, overexpression protection experiments Immunity High 9430226
1997 TRAIL-R1 (DR4) and TRAIL-R2 (DR5) both bind the adaptor molecules FADD and TRADD, and both death signals are blocked by dominant-negative FADD and by the FLICE-inhibitory protein FLIP. TRAIL-R1 can associate with TRAIL-R2, suggesting possible signaling through heteroreceptor complexes. Recruitment of TRADD explains the potent NF-κB activation observed from TRAIL receptors. Co-immunoprecipitation, dominant-negative FADD and FLIP overexpression, NF-κB reporter assays Immunity High 9430228
1997 Two additional TRAIL receptors, TRAIL-R2 (DR5, containing a death domain) and TRAIL-R3 (lacking a death domain), were identified. DR5 engages the apoptotic pathway independently of FADD/MORT1. TRAIL-R3, by competing for TRAIL binding, inhibits TRAIL-induced apoptosis, functioning as an antagonistic decoy receptor. cDNA library screening, apoptosis assays, FADD interaction studies, competition binding assays The Journal of biological chemistry High 9325248
1997 TRAIL-R3 (DcR1) was cloned and shown to be a GPI-linked plasma membrane protein with high-affinity TRAIL binding but lacking a cytoplasmic domain. TRAIL-R3 does not induce apoptosis and shows restricted expression in peripheral blood lymphocytes and spleen. The TRAIL-R3 gene maps to chromosome 8p22-21. cDNA cloning, quantitative binding studies, GPI-anchor characterization, apoptosis assays The Journal of experimental medicine High 9314565
1999 The crystal structure of the Apo2L/TRAIL homotrimer in complex with the ectodomain of DR5 was solved. Three elongated DR5 receptors bind in long crevices between pairs of monomers of the trimeric ligand. The binding interface is divided into two distinct patches (near the membrane-proximal and membrane-distal ends), both containing residues critical for high-affinity binding. Comparison to the lymphotoxin-receptor complex revealed general principles of binding in the TNF receptor superfamily. X-ray crystallography Molecular cell High 10549288
2000 FADD/MORT1 and caspase-8 are recruited to both TRAIL-R1 and TRAIL-R2 in a ligand-dependent manner to form the TRAIL death-inducing signaling complex (DISC). FADD/MORT1 and caspase-8 are recruited to the two TRAIL receptors independently of each other. FADD- and caspase-8-deficient Jurkat cells expressing only TRAIL-R2 were resistant to TRAIL-induced apoptosis, establishing that both proteins are essential for TRAIL-R2-mediated apoptosis. Native DISC immunoprecipitation, differential receptor precipitation, genetic knockout cell lines (FADD-deficient, caspase-8-deficient) Immunity High 10894160
2002 Caspase-10 is recruited to both the native TRAIL DISC and the native CD95 DISC in a FADD-dependent manner and is activated at these complexes. However, caspase-10 cannot functionally substitute for caspase-8: caspase-8-deficient cells could not be rescued by caspase-10 overexpression. Caspase-10 is cleaved during CD95-induced apoptosis of activated T cells. Native DISC immunoprecipitation, genetic knockout cells (FADD-deficient), caspase-10 overexpression rescue experiments, primary T cell assays The EMBO journal High 12198154
2002 FOXO forkhead transcription factors FKHRL1 and FKHR directly regulate TRAIL (TNFSF10) expression. The FKHRL1-responsive element in the TRAIL promoter was mapped to nucleotides -138 to -121. Loss of PTEN in prostate cancer leads to decreased FOXO activity and reduced TRAIL expression in metastatic prostate tumors, linking the PI3K-Akt pathway to TRAIL gene regulation. Microarray gene expression, adenoviral FOXO overexpression, TRAIL promoter reporter constructs, chromatin analysis, human tumor immunohistochemistry The Journal of biological chemistry High 12351634
2002 PPAR-γ ligands sensitize tumor cells (but not normal cells) to TRAIL-induced apoptosis by reducing FLIP protein levels through ubiquitination and proteasome-dependent degradation, without affecting FLIP mRNA. This mechanism is PPAR-γ-independent (active with both agonists and antagonists and dominant-negative PPAR-γ) and does not involve NF-κB. PPAR-γ agonist/antagonist treatment, dominant-negative PPAR-γ, FLIP ubiquitination assays, proteasome inhibitor experiments, mRNA vs. protein analysis The Journal of biological chemistry High 11940602
2004 HDAC inhibitors induce TRAIL (TNFSF10) expression in acute myeloid leukemia (AML) cells by directly activating the TNFSF10 promoter, thereby triggering tumor-selective death signaling. RNA interference showed that TRAIL induction, p21 induction, and differentiation are separable activities of HDACIs. Normal CD34+ progenitor cells did not undergo apoptosis. HDAC inhibitor treatment, TRAIL promoter reporter assays, RNA interference (siRNA), chromatin immunoprecipitation, primary AML blast assays Nature medicine High 15619633
2004 FLIP protein potently blocks TRAIL-mediated cell death by interfering with caspase-8 activation at the DISC. Pharmacologic down-regulation of FLIP sensitizes tumor cells to TRAIL-induced apoptosis. FLIP overexpression and knockdown, caspase-8 activation assays, apoptosis assays Vitamins and hormones Medium 15110178
2005 TRAIL-receptor-selective mutant forms of TRAIL were synthesized that selectively bind TRAIL-R1 or TRAIL-R2. The selectivity in inducing apoptosis is due to selective receptor binding and formation of a death-inducing signaling complex (DISC) with the cognate receptor. Using these mutants, primary chronic lymphocytic leukemia and mantle cell lymphoma cells were shown to signal apoptosis almost exclusively through TRAIL-R1. Synthetic receptor-selective TRAIL mutants, apoptosis assays, DISC formation analysis, primary patient CLL and MCL cells Cancer research High 16357130
2007 O-glycosylation of death receptors DR4 and DR5 by the peptidyl O-glycosyltransferase GALNT14 controls tumor-cell sensitivity to Apo2L/TRAIL. Biochemical analysis identified O-(GalNAc-Gal-sialic acid) structures on the DR5 ectodomain at conserved extracellular sites. Progressive mutation of these sites attenuated apoptotic signaling. O-glycosylation promoted ligand-stimulated clustering of DR4 and DR5, which mediated recruitment and activation of caspase-8. GALNT14 RNAi and overexpression, DR5 mass spectrometry glycosylation mapping, site-directed mutagenesis of O-glycosylation sites, receptor clustering assays, caspase-8 activation assays Nature medicine High 17167167
2008 The transcription factor Sp1 is responsible for TRAIL (TNFSF10) induction by the HDAC inhibitor MS275 alone or in combination with Adriamycin in breast cancer cells. Chromatin immunoprecipitation confirmed Sp1 binding to the TRAIL promoter. Knockdown of TRAIL by siRNA decreased MS275-mediated Adriamycin-induced caspase activation, and Sp1-knockout MEFs were resistant to combined treatment. TRAIL promoter reporter constructs, chromatin immunoprecipitation, Sp1 siRNA knockdown, Sp1-knockout mouse embryonic stem cells, caspase activation assays Cancer research High 18701496
2009 TRAIL-induced autophagy in untransformed epithelial cells is mediated by AMPK, which inhibits mTORC1. TRAIL-induced AMPK activation is independent of LKB1 and CaMKK-β but depends on TAK1 and TAK1-binding subunit 2. This cytoprotective autophagy pathway contributes to the resistance of normal (untransformed) cells to TRAIL-induced apoptosis. Genetic knockdown (siRNA for TAK1, LKB1, CaMKK-β), AMPK activity assays, mTORC1 signaling assays, autophagy monitoring, apoptosis assays in normal vs. transformed cells The EMBO journal High 19197243
2009 Death receptor ligation by TRAIL/DR4/DR5 induces polyubiquitination of caspase-8 through a cullin3 (CUL3)-based E3 ligase that is recruited to the DISC. CUL3-mediated caspase-8 polyubiquitination requires RBX1; the deubiquitinase A20 reverses this modification. The ubiquitin-binding protein p62/sequestosome-1 promotes aggregation of CUL3-modified caspase-8 within p62 foci, leading to full activation, processing, and commitment to apoptosis. Co-immunoprecipitation of native DISC, ubiquitination assays, CUL3/RBX1/A20/p62 RNAi knockdown, caspase-8 processing assays, confocal microscopy of p62 foci Cell High 19427028
2003 TRAIL regulates normal erythroid maturation through an ERK-dependent pathway. TRAIL-R2 (but not TRAIL-R1, R3, or R4) is expressed throughout erythroid differentiation from CD34+ progenitors. TRAIL stimulates ERK1/2 (but not p38 MAPK or JNK) signaling in erythroblasts, and the ERK inhibitor PD98059 (but not the pan-caspase inhibitor z-VAD or p38 inhibitor SB203580) reverses the anti-differentiative effect of TRAIL on erythroid maturation. Flow cytometry (receptor expression), recombinant TRAIL treatment, ERK/p38/JNK phosphorylation assays, pharmacological pathway inhibitors, morphological differentiation assays Blood High 12969966
2010 TRAIL-R4 expressed endogenously or ectopically inhibits TRAIL-induced apoptosis. Chemotherapy restores TRAIL sensitivity in TRAIL-R4-expressing cells primarily at the DISC level through enhanced caspase-8 recruitment and activation. The sensitization is compromised by c-FLIP expression and is independent of mitochondria. TRAIL-R4 cooperates with c-FLIP to inhibit TRAIL-induced cell death, and TRAIL-R4 expression prevents TRAIL-induced tumor regression in vivo. Ectopic TRAIL-R4 expression, DISC immunoprecipitation, caspase-8 recruitment assays, c-FLIP manipulation, mitochondria-independent cell death assays, xenograft tumor models Cell death and differentiation High 21072058
2014 TRAF2 acts as a negative regulator of TRAIL-induced apoptosis and necroptosis. TRAF2 knockdown sensitizes keratinocytes to TRAIL-induced apoptosis. In cells lacking RIP3, TRAF2 knockdown sensitizes to TRAIL-induced caspase-dependent apoptosis. In RIP3-expressing cells, TRAF2 knockdown additionally sensitizes to TRAIL-induced necroptosis. TRAIL-induced necroptosis is independent of endogenous TNF/TNFR signaling. TWEAK-mediated depletion of cytosolic TRAF2 complexes strongly sensitizes for TRAIL-induced necroptosis. TRAF2 siRNA knockdown, zVAD-fmk (pan-caspase inhibitor) protection assays, necrostatin-1 (RIP1 inhibitor), RIP3-stable transfectants, TNFR2-Fc and anti-TNFα blocking experiments Cell death & disease High 25299769
2014 DAPK2 (death-associated protein kinase 2) is a modulator of TRAIL signaling. Genetic ablation of DAPK2 by RNAi causes NF-κB phosphorylation and transcriptional activation, leading to induction of DR4 and DR5 expression. Increased DR4/DR5 surface expression sensitizes resistant cancer cells to TRAIL-induced killing in a p53-independent manner. DAPK2 siRNA knockdown, NF-κB reporter and phosphorylation assays, DR4/DR5 surface flow cytometry, p53-deficient cell lines, TRAIL cytotoxicity assays Cell death and differentiation Medium 25012503
2015 Poly-ADP-ribosylation of HMGB1 by PARP1 is required for TRAIL (TNFSF10)-induced HMGB1 cytoplasmic translocation and subsequent HMGB1-BECN1 complex formation, which drives cytoprotective autophagy. Pharmacological inhibition or knockdown of PARP1 inhibits HMGB1-mediated autophagy, increases apoptosis, and enhances TRAIL anticancer activity in vitro and in a tumor model. Thus PARP1-dependent HMGB1 ADP-ribosylation maintains a homeostatic balance between autophagy and apoptosis during TRAIL signaling. PARP1 pharmacological inhibition and siRNA knockdown, HMGB1 ADP-ribosylation assays, co-immunoprecipitation (HMGB1-BECN1 complex), autophagy monitoring, apoptosis assays, subcutaneous tumor model Autophagy High 25607248
2016 Hepatitis B virus X protein (HBx) evades TRAIL (TNFSF10)-mediated antiviral immunity by promoting autophagy-mediated lysosomal degradation of TNFRSF10B (DR5). HBx directly interacts with TNFRSF10B and recruits it to phagophores (autophagosome precursors), acting as an autophagy receptor-like molecule that promotes TNFRSF10B association with LC3B. HBx also functions as an autophagy inducer. Inhibition of autophagy enhances susceptibility of HBx-infected hepatocytes to TRAIL. Immunoprecipitation and GST affinity isolation (HBx-TNFRSF10B interaction), tandem-fluorescence LC3B assay, LC3B/SQSTM1 immunoblotting, LC3B knockdown, pharmacological autophagy inhibition, liver tissue from chronic HBV patients Autophagy High 27740879
2016 TRAIL-mediated necroptosis shares signaling components with TNF-mediated necroptosis including acid and neutral sphingomyelinases, HtrA2/Omi, Atg5, and vacuolar H+-ATPase. However, TRAIL-mediated necroptosis differs from TNF-mediated necroptosis in being independent of UCH-L1 and Atg16L1, and does not require receptor internalization or endosome-lysosome acidification. Bcl-XL overexpression specifically diminishes TRAIL-induced necroptosis, suggesting differential mitochondrial involvement. Depletion of p38α increases both types of cell death. siRNA knockdown of signaling components, pharmacological inhibitors, Bcl-2/Bcl-XL overexpression, RIP3-expressing cell systems, necroptosis quantification Molecular and cellular biology Medium 27528614
2019 DR4 (TRAIL-R1) is O-GlcNAcylated at Ser424 within its death domain, and this modification is essential for TRAIL-induced apoptosis and necrosis. Ser424 mutations identified from cancer patients caused TRAIL resistance. O-GlcNAcylation-defective DR4 failed to form DISC/necrosome and could not translocate to aggregated receptor-clustering platforms. DR5 is not O-GlcNAcylated by TRAIL treatment, discriminating DR4 from DR5-mediated signaling. Promoting DR4 O-GlcNAcylation (with 2-deoxy-D-glucose or high glucose) sensitized resistant cancer cells to TRAIL. O-GlcNAc transferase knockdown, DR4 site-directed mutagenesis (Ser424), cancer patient cDNA library screen (TCGA), DR5-neutralizing antibody, DISC/necrosome co-immunoprecipitation, receptor clustering assays, glucose-modulated O-GlcNAcylation Cancer research High 30987996
2014 Nuclear TRAIL-R2 (nTRAIL-R2) originates from the plasma membrane via TRAIL-dependent clathrin-mediated endocytosis. nTRAIL-R2 interacts with the nucleo-cytoplasmic shuttle protein Exportin-1/CRM-1; mutation of a putative nuclear export sequence (NES) in TRAIL-R2 or inhibition of CRM-1 by Leptomycin-B causes nuclear accumulation of TRAIL-R2. Nuclear TRAIL-R2 inhibits processing of primary let-7 miRNA (pri-let-7) by interacting with accessory proteins of the Microprocessor complex, thereby decreasing mature let-7 and enhancing malignancy. Co-immunoprecipitation (nTRAIL-R2 with Microprocessor components), NES mutagenesis, Leptomycin-B CRM-1 inhibition, nuclear fractionation, let-7 miRNA processing assays Cell death & disease Medium 25165876
2019 TRAIL induces nuclear translocation of TRAIL-R1 and TRAIL-R2 from the plasma membrane via clathrin-dependent endocytosis in a TRAIL-dependent manner. Nuclear trafficking is rapid and involves interaction of nTRAIL-R2 with Exportin-1/CRM-1. NES mutation in TRAIL-R2 or CRM-1 inhibition (Leptomycin-B) causes nuclear accumulation. TRAIL-R1 and TRAIL-R2 constitutively localize to chromatin, which is strongly enhanced by TRAIL treatment. Cell surface biotinylation and intracellular tracking, clathrin inhibition, co-immunoprecipitation (TRAIL-R2/Exportin-1), NES mutagenesis, Leptomycin-B treatment, chromatin fractionation, immunofluorescence Cancers High 31416165
2021 A subset of LAMP1+TRAIL+ astrocytes limits CNS inflammation by inducing T cell apoptosis through TRAIL-DR5 signaling. In homeostatic conditions, TRAIL expression in astrocytes is driven by IFNγ produced by meningeal NK cells, which is modulated by the gut microbiome. T cells and microglia repress TRAIL expression in astrocytes during inflammation. CRISPR-Cas9-based in vivo genetic perturbations confirmed the role of astrocytic TRAIL in T cell killing. High-throughput flow cytometry screening, single-cell RNA sequencing, CRISPR-Cas9 in vivo genetic perturbations, T cell apoptosis assays (TRAIL-DR5 blocking), germ-free mouse models Nature High 33408417
2003 In intestinal epithelial cells, TRAIL promotes differentiation rather than apoptosis despite expression of TRAIL-R1 and TRAIL-R2. TRAIL increases expression of cyclin-dependent kinase inhibitors p21 and p27 and the differentiation marker DPPIV. The differentiation-inducing activity was abolished by pre-incubation with Fc-TRAIL-R2 chimera, establishing TRAIL-R2 as the functional receptor mediating this non-apoptotic effect. Flow cytometry (receptor expression), recombinant TRAIL treatment, Fc-TRAIL-R2 chimera blocking, cell cycle analysis (p21/p27/DPPIV expression), differentiation assays Journal of cellular physiology Medium 16245299
2004 Megakaryocytes synthesize TRAIL during differentiation via increased transcriptional activity of the TRAIL promoter, and activated platelets express both membrane-bound and soluble TRAIL. Lineage-specific upregulation of TRAIL expression during megakaryocyte differentiation is mediated at the transcriptional level. Immunoprecipitation, ELISA, flow cytometry, RT-PCR, TRAIL promoter/reporter transient transfection, in vitro megakaryocyte differentiation Experimental hematology Medium 15539085
2021 miR-24-3p from M2 macrophage-derived exosomes targets and inhibits Tnfsf10 (TRAIL) mRNA in cardiomyocytes. A direct binding relationship between miR-24-3p and the Tnfsf10 3'UTR was demonstrated. In a septic mouse model, Tnfsf10 expression is elevated in myocardial tissue; exosomal miR-24-3p or Tnfsf10 siRNA knockdown improved cardiac function and reduced cardiomyocyte apoptosis. Luciferase reporter assay (miR-24-3p binding to Tnfsf10 3'UTR), exosome isolation and miR-24-3p modification, Tnfsf10 siRNA knockdown, LPS-induced sepsis mouse model, cardiac function assays Molecular immunology Medium 34933177
2014 Neutralization of TNFSF10 (TRAIL) by a monoclonal antibody in the 3xTg-AD Alzheimer's disease mouse model attenuates amyloid-β-induced neurotoxicity, improves cognitive function (Morris water maze, novel object recognition), and reduces expression of TNFSF10, amyloid-β, inflammatory mediators, and GFAP in the hippocampus. This establishes TNFSF10 as a mediator of amyloid-β neurotoxicity. Neutralizing monoclonal antibody administration, transgenic mouse model (3xTg-AD), Morris water maze and novel object recognition behavioral tests, protein expression analysis (TNFSF10, Aβ, GFAP, inflammatory mediators) Brain Medium 25472798
2002 TRAIL-mediated apoptosis of hepatocytes in vivo is triggered through TRAIL receptor DR5 and requires viral infection; uninfected hepatocytes in vivo are resistant to TRAIL-mediated apoptosis. Overexpression of TRAIL in the liver after viral infection is independent of lymphocytes, NK cells, and Kupffer cells, indicating a paracrine hepatocyte-autonomous mechanism against virally infected cells. Adenoviral hepatitis mouse model, DR5 blocking/knockout studies, liver histology, NK/lymphocyte depletion experiments, in vitro vs. in vivo TRAIL sensitivity comparison FASEB journal Medium 12475902
2007 Dengue virus (DV) induces TRAIL expression in immune cells and endothelial cells via an intact type I interferon signaling pathway. TRAIL functions as an antiviral protein: anti-TRAIL antibody treatment increased DV RNA accumulation, while recombinant TRAIL inhibited DV titers in dendritic cells by an apoptosis-independent mechanism. Affymetrix GeneChip microarray, anti-TRAIL antibody treatment, recombinant TRAIL treatment, DV RNA quantification and titer measurement, interferon pathway blockade Journal of virology Medium 17913827
2002 NF-κB transcription factors are key regulators of TRAIL expression in lymphocytes. TRAIL transcription is activated through an interferon-response element in its promoter. Decoy receptors TRAIL-R3/DcR1 and TRAIL-R4/DcR2 lack functional death domains and do not mediate apoptosis, providing a regulatory mechanism for differential sensitivity. NF-κB reporter assays, promoter analysis with interferon-response element, TRAIL receptor expression studies Cytokine & growth factor reviews Low 12486874

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proceedings of the National Academy of Sciences of the United States of America 3272 9520411
1995 Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 2449 8777713
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
1996 Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. The Journal of biological chemistry 1549 8663110
1997 The receptor for the cytotoxic ligand TRAIL. Science (New York, N.Y.) 1489 9082980
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1997 An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science (New York, N.Y.) 1312 9242610
2003 Mechanisms of caspase activation. Current opinion in cell biology 1028 14644197
1997 TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. The EMBO journal 967 9311998
2003 Apo2L/TRAIL and its death and decoy receptors. Cell death and differentiation 711 12655296
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
1997 The novel receptor TRAIL-R4 induces NF-kappaB and protects against TRAIL-mediated apoptosis, yet retains an incomplete death domain. Immunity 700 9430226
2000 FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2. Immunity 683 10894160
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2002 Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo. Nature medicine 623 12118245
1997 TRAIL receptors 1 (DR4) and 2 (DR5) signal FADD-dependent apoptosis and activate NF-kappaB. Immunity 598 9430228
2004 A small molecule Smac mimic potentiates TRAIL- and TNFalpha-mediated cell death. Science (New York, N.Y.) 562 15353805
1997 Cloning and characterization of TRAIL-R3, a novel member of the emerging TRAIL receptor family. The Journal of experimental medicine 529 9314565
2009 Cullin3-based polyubiquitination and p62-dependent aggregation of caspase-8 mediate extrinsic apoptosis signaling. Cell 511 19427028
2007 Death-receptor O-glycosylation controls tumor-cell sensitivity to the proapoptotic ligand Apo2L/TRAIL. Nature medicine 480 17767167
1997 Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL. The Journal of biological chemistry 478 9325248
2003 Apo2L/TRAIL: apoptosis signaling, biology, and potential for cancer therapy. Cytokine & growth factor reviews 471 12787570
2004 Tumor-selective action of HDAC inhibitors involves TRAIL induction in acute myeloid leukemia cells. Nature medicine 452 15619633
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Citrus limon-derived nanovesicles inhibit cancer cell proliferation and suppress CML xenograft growth by inducing TRAIL-mediated cell death. Oncotarget 393 26098775
1999 Triggering cell death: the crystal structure of Apo2L/TRAIL in a complex with death receptor 5. Molecular cell 378 10549288
2007 TRAIL signalling: decisions between life and death. The international journal of biochemistry & cell biology 377 17403612
2008 Ligand-based targeting of apoptosis in cancer: the potential of recombinant human apoptosis ligand 2/Tumor necrosis factor-related apoptosis-inducing ligand (rhApo2L/TRAIL). Journal of clinical oncology : official journal of the American Society of Clinical Oncology 347 18640940
2009 TAK1 activates AMPK-dependent cytoprotective autophagy in TRAIL-treated epithelial cells. The EMBO journal 337 19197243
2003 Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways. Oncogene 331 12761501
2009 Mesenchymal stem cell delivery of TRAIL can eliminate metastatic cancer. Cancer research 325 19435900
2002 FOXO proteins regulate tumor necrosis factor-related apoptosis inducing ligand expression. Implications for PTEN mutation in prostate cancer. The Journal of biological chemistry 314 12351634
2002 Caspase-10 is recruited to and activated at the native TRAIL and CD95 death-inducing signalling complexes in a FADD-dependent manner but can not functionally substitute caspase-8. The EMBO journal 280 12198154
2002 An inducible pathway for degradation of FLIP protein sensitizes tumor cells to TRAIL-induced apoptosis. The Journal of biological chemistry 273 11940602
2021 Gut-licensed IFNγ+ NK cells drive LAMP1+TRAIL+ anti-inflammatory astrocytes. Nature 265 33408417
1997 Characterization of two receptors for TRAIL. FEBS letters 241 9373179
2018 Developing TRAIL/TRAIL death receptor-based cancer therapies. Cancer metastasis reviews 206 29541897
2003 TRAIL-induced signalling and apoptosis. Toxicology letters 192 12628743
2015 Trailing TRAIL Resistance: Novel Targets for TRAIL Sensitization in Cancer Cells. Frontiers in oncology 183 25883904
2001 How melanoma cells evade trail-induced apoptosis. Nature reviews. Cancer 182 11905805
2009 TNF-related apoptosis-inducing ligand (TRAIL): a new path to anti-cancer therapies. European journal of pharmacology 155 19836385
2006 The clinical trail of TRAIL. European journal of cancer (Oxford, England : 1990) 148 16884904
2003 Acceleration of human neutrophil apoptosis by TRAIL. Journal of immunology (Baltimore, Md. : 1950) 144 12517970
1997 Cell death: TRAIL and its receptors. Current biology : CB 140 9382834
2005 TRAIL receptor-selective mutants signal to apoptosis via TRAIL-R1 in primary lymphoid malignancies. Cancer research 137 16357130
2010 TRAIL receptor signaling and therapeutics. Expert opinion on therapeutic targets 126 20819019
2001 The potential of TRAIL for cancer chemotherapy. Apoptosis : an international journal on programmed cell death 124 11388668
2003 TRAIL regulates normal erythroid maturation through an ERK-dependent pathway. Blood 110 12969966
2002 Involvement of TRAIL and its receptors in viral hepatitis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 104 12475902
2008 The death ligand TRAIL in diabetic nephropathy. Journal of the American Society of Nephrology : JASN 100 18287563
2008 Mcl-1: a gateway to TRAIL sensitization. Cancer research 98 18381408
2019 The TRAIL to cancer therapy: Hindrances and potential solutions. Critical reviews in oncology/hematology 88 31561055
2023 The Role of TRAIL in Apoptosis and Immunosurveillance in Cancer. Cancers 79 37345089
2002 On the TRAIL to apoptosis. Cytokine & growth factor reviews 77 12486874
2012 Regulation of the human TRAIL gene. Cancer biology & therapy 75 22892844
1999 Expression of TRAIL and its receptors in human brain tumors. Biochemical and biophysical research communications 75 10198234
2019 Nutrition for Ultramarathon Running: Trail, Track, and Road. International journal of sport nutrition and exercise metabolism 73 30943823
2014 TRAF2 inhibits TRAIL- and CD95L-induced apoptosis and necroptosis. Cell death & disease 71 25299769
2014 Neutralization of TNFSF10 ameliorates functional outcome in a murine model of Alzheimer's disease. Brain : a journal of neurology 70 25472798
2010 Chemotherapy overcomes TRAIL-R4-mediated TRAIL resistance at the DISC level. Cell death and differentiation 66 21072058
2014 TRAIL-R2-specific antibodies and recombinant TRAIL can synergise to kill cancer cells. Oncogene 64 24909167
2007 Clearing the TRAIL for Cancer Therapy. Cancer cell 64 17613431
2007 Expression, regulation and function of trail in atherosclerosis. Biochemical pharmacology 61 18061141
2001 Potential and caveats of TRAIL in cancer therapy. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 60 11991679
2016 Aptamer-miRNA-212 Conjugate Sensitizes NSCLC Cells to TRAIL. Molecular therapy. Nucleic acids 58 27111415
1999 The oxygen trail: tissue oxygenation. British medical bulletin 56 10695081
2007 TRAIL is a novel antiviral protein against dengue virus. Journal of virology 55 17913827
1994 Interaction of hepatitis B virus X protein with a serine protease, tryptase TL2 as an inhibitor. Oncogene 55 8290248
2016 Hepatitis B virus-triggered autophagy targets TNFRSF10B/death receptor 5 for degradation to limit TNFSF10/TRAIL response. Autophagy 54 27740879
2014 Compartmentalization of TNF-related apoptosis-inducing ligand (TRAIL) death receptor functions: emerging role of nuclear TRAIL-R2. Cell death & disease 53 25165876
2006 TRAIL death receptors and cancer therapeutics. Toxicology and applied pharmacology 53 17240413
2005 Effective gene-virotherapy for complete eradication of tumor mediated by the combination of hTRAIL (TNFSF10) and plasminogen k5. Molecular therapy : the journal of the American Society of Gene Therapy 53 15771956
2004 FLIP protein and TRAIL-induced apoptosis. Vitamins and hormones 53 15110178
2019 TRAIL-based gene delivery and therapeutic strategies. Acta pharmacologica Sinica 52 31444476
2015 On the organ trail: insights into organ regeneration in the planarian. Current opinion in genetics & development 52 25703843
2015 Poly-ADP-ribosylation of HMGB1 regulates TNFSF10/TRAIL resistance through autophagy. Autophagy 51 25607248
2012 Targeting death receptor TRAIL-R2 by chalcones for TRAIL-induced apoptosis in cancer cells. International journal of molecular sciences 49 23203129
2007 The role of TRAIL/TRAIL receptors in central nervous system pathology. Frontiers in bioscience : a journal and virtual library 48 17485268
2012 Resistance to TRAIL and how to surmount it. Immunologic research 47 22407575
2011 Targeting Apo2L/TRAIL receptors by soluble Apo2L/TRAIL. Cancer letters 44 21220186
2010 Triptolide and TRAIL combination enhances apoptosis in cholangiocarcinoma. The Journal of surgical research 44 20691980
2009 HIV induces TRAIL sensitivity in hepatocytes. PloS one 44 19247452
2005 On the TRAIL of a new therapy for leukemia. Leukemia 44 16224489
2003 Adenovirus-TRAIL can overcome TRAIL resistance and induce a bystander effect. Cancer gene therapy 44 12833134
2006 Following the TRAIL to apoptosis. Immunologic research 42 17172650
2007 The NO TRAIL to YES TRAIL in cancer therapy (review). International journal of oncology 41 17786298
2006 On the production of TNF-related apoptosis-inducing ligand (TRAIL/Apo-2L) by human neutrophils. Journal of leukocyte biology 39 16574768
2019 Upregulation of long noncoding TNFSF10 contributes to osteoarthritis progression through the miR-376-3p/FGFR1 axis. Journal of cellular biochemistry 38 31297857
2017 Nanocarriers for TRAIL delivery: driving TRAIL back on track for cancer therapy. Nanoscale 38 28914952
2009 Down-regulation of HSP27 sensitizes TRAIL-resistant tumor cell to TRAIL-induced apoptosis. Lung cancer (Amsterdam, Netherlands) 38 19540014
2008 Sp1-mediated TRAIL induction in chemosensitization. Cancer research 38 18701496
2006 Involvement of TRAIL/TRAIL-receptors in human intestinal cell differentiation. Journal of cellular physiology 38 16245299
2021 Revisiting the role of TRAIL/TRAIL-R in cancer biology and therapy. Future oncology (London, England) 37 33401962
2006 TRAIL receptor-targeted therapy. Future oncology (London, England) 37 16922616
2000 Expression and antitumor effects of TRAIL in human cholangiocarcinoma. Hepatology (Baltimore, Md.) 37 10960444
2021 Targeting the miRNA-155/TNFSF10 network restrains inflammatory response in the retina in a mouse model of Alzheimer's disease. Cell death & disease 36 34611142
2014 DAPK2 is a novel modulator of TRAIL-induced apoptosis. Cell death and differentiation 35 25012503
2004 Regulation of sensitivity to TRAIL by the PTEN tumor suppressor. Vitamins and hormones 34 15110188
2023 Therapeutic targeting of TRAIL death receptors. Biochemical Society transactions 32 36629496
2002 A trail of research on potassium. Kidney international 32 12371944
2020 On the TRAIL of Better Therapies: Understanding TNFRSF Structure-Function. Cells 31 32245106
2004 Expression of TNF-related apoptosis-inducing ligand (TRAIL) in megakaryocytes and platelets. Experimental hematology 31 15539085
1995 A research trail over half a century. Annual review of pharmacology and toxicology 31 7598488
2021 Overcoming TRAIL Resistance for Glioblastoma Treatment. Biomolecules 30 33919846
2008 TRAIL death receptors as tumor suppressors and drug targets. Cell cycle (Georgetown, Tex.) 30 18469516
2007 Apo2L/TRAIL and immune regulation. Frontiers in bioscience : a journal and virtual library 30 17127445
2021 Cardioprotection of M2 macrophages-derived exosomal microRNA-24-3p/Tnfsf10 axis against myocardial injury after sepsis. Molecular immunology 29 34933177
2018 TRAIL pathway targeting therapeutics. Expert review of precision medicine and drug development 28 30740527
2009 Human monomeric antibody fragments to TRAIL-R1 and TRAIL-R2 that display potent in vitro agonism. mAbs 28 20068388
2004 Modulation of TRAIL signaling for cancer therapy. Vitamins and hormones 28 15110182
2016 Differences and Similarities in TRAIL- and Tumor Necrosis Factor-Mediated Necroptotic Signaling in Cancer Cells. Molecular and cellular biology 27 27528614
2018 Divergent Roles for TRAIL in Lung Diseases. Frontiers in medicine 26 30101145
2016 A Purinergic Trail for Metastases. Trends in pharmacological sciences 26 27989503
2008 TRAIL and Taurolidine induce apoptosis and decrease proliferation in human fibrosarcoma. Journal of experimental & clinical cancer research : CR 26 19077262
2016 Identification of Mitoxantrone as a TRAIL-sensitizing agent for Glioblastoma Multiforme. Cancer biology & therapy 25 27029345
2015 Novel TRAIL sensitizer Taraxacum officinale F.H. Wigg enhances TRAIL-induced apoptosis in Huh7 cells. Molecular carcinogenesis 25 25647515
2016 Nucleic Acid Engineering: RNA Following the Trail of DNA. ACS combinatorial science 23 26735596
2012 Resistance to TRAIL is mediated by DARPP-32 in gastric cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 23 22589394
2021 Splicing reprogramming of TRAIL/DISC-components sensitizes lung cancer cells to TRAIL-mediated apoptosis. Cell death & disease 22 33731677
2011 Therapeutic targeting of CD95 and the TRAIL death receptors. Recent patents on anti-cancer drug discovery 21 21762072
2019 Co-delivery of TRAIL and siHSP70 using hierarchically modular assembly formulations achieves enhanced TRAIL-resistant cancer therapy. Journal of controlled release : official journal of the Controlled Release Society 20 31078569
2015 Delivery of tumor-homing TRAIL sensitizer with long-acting TRAIL as a therapy for TRAIL-resistant tumors. Journal of controlled release : official journal of the Controlled Release Society 20 26381901
2024 Enhanced anticancer efficacy of TRAIL-conjugated and odanacatib-loaded PLGA nanoparticles in TRAIL resistant cancer. Biomaterials 19 39106819
2019 DR4-Ser424 O-GlcNAcylation Promotes Sensitization of TRAIL-Tolerant Persisters and TRAIL-Resistant Cancer Cells to Death. Cancer research 19 30987996
2009 The Par-4-GRP78 TRAIL, more twists and turns. Cancer biology & therapy 19 19823030
2008 Role of IG20 splice variants in TRAIL resistance. Clinical cancer research : an official journal of the American Association for Cancer Research 19 18223207
2004 Promoter of TRAIL-R2 gene. Vitamins and hormones 19 15110170
1983 The tL2 cluster of transcription termination sites between genes bet and ral of coliphage lambda. Virology 19 6220515
2019 TRAIL Induces Nuclear Translocation and Chromatin Localization of TRAIL Death Receptors. Cancers 18 31416165