RGD Reference Report - Playing the DISC: turning on TRAIL death receptor-mediated apoptosis in cancer. - Rat Genome Database

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Playing the DISC: turning on TRAIL death receptor-mediated apoptosis in cancer.

Authors: Pennarun, B  Meijer, A  De Vries, EG  Kleibeuker, JH  Kruyt, F  De Jong, S 
Citation: Pennarun B, etal., Biochim Biophys Acta. 2010 Apr;1805(2):123-40. Epub 2009 Dec 2.
RGD ID: 4143171
Pubmed: PMID:19961901   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbcan.2009.11.004   (Journal Full-text)

Formation of the pro-apoptotic death-inducing signaling complex (DISC) can be initiated in cancer cells via binding of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to its two pro-apoptotic receptors, TRAIL receptor 1 (TRAIL-R1) and TRAIL-R2. Primary components of the DISC are trimerized TRAIL-R1/-R2, FADD, caspase 8 and caspase 10. The anti-apoptotic protein FLIP can also be recruited to the DISC to replace caspase 8 and form an inactive complex. Caspase 8/10 processing at the DISC triggers the caspase cascade, which eventually leads to apoptotic cell death. Besides TRAIL, TRAIL-R1- or TRAIL-R2-selective variants of TRAIL and agonistic antibodies have been designed. These ligands are of interest as anti-cancer agents since they selectively kill tumor cells. To increase tumor sensitivity to TRAIL death receptor-mediated apoptosis and to overcome drug resistance, TRAIL receptor ligands have already been combined with various therapies in preclinical models. In this review, we discuss factors influencing the initial steps of the TRAIL apoptosis signaling pathway, focusing on mechanisms modulating DISC assembly and caspase activation at the DISC. These insights will direct rational design of drug combinations with TRAIL receptor ligands to maximize DISC signaling.



Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BIDHumanTrail mediated signaling pathway   TAS  RGD 
BidRatTrail mediated signaling pathway   ISOBID (Homo sapiens) RGD 
BidMouseTrail mediated signaling pathway   ISOBID (Homo sapiens) RGD 
CASP3HumanTrail mediated signaling pathway   TAS  RGD 
CASP7HumanTrail mediated signaling pathway   TAS  RGD 
CASP8HumanTrail mediated signaling pathway   TAS  RGD 
CFLARHumanTrail mediated signaling pathway   TAS  RGD 
Casp3RatTrail mediated signaling pathway   ISOCASP3 (Homo sapiens) RGD 
Casp3MouseTrail mediated signaling pathway   ISOCASP3 (Homo sapiens) RGD 
Casp7RatTrail mediated signaling pathway   ISOCASP7 (Homo sapiens) RGD 
Casp7MouseTrail mediated signaling pathway   ISOCASP7 (Homo sapiens) RGD 
Casp8RatTrail mediated signaling pathway   ISOCASP8 (Homo sapiens) RGD 
Casp8MouseTrail mediated signaling pathway   ISOCASP8 (Homo sapiens) RGD 
CflarRatTrail mediated signaling pathway   ISOCFLAR (Homo sapiens) RGD 
CflarMouseTrail mediated signaling pathway   ISOCFLAR (Homo sapiens) RGD 
FADDHumanTrail mediated signaling pathway   TAS  RGD 
FaddRatTrail mediated signaling pathway   ISOFADD (Homo sapiens) RGD 
FaddMouseTrail mediated signaling pathway   ISOFADD (Homo sapiens) RGD 
TNFRSF10AHumanTrail mediated signaling pathway   TAS  RGD 
TNFRSF10BHumanTrail mediated signaling pathway   TAS  RGD 
TNFSF10HumanTrail mediated signaling pathway   TAS  RGD 
Tnfrsf10bRatTrail mediated signaling pathway   ISOTNFRSF10B (Homo sapiens) RGD 
Tnfrsf10bMouseTrail mediated signaling pathway   ISOTNFRSF10B (Homo sapiens) RGD 
Tnfsf10RatTrail mediated signaling pathway   ISOTNFSF10 (Homo sapiens) RGD 
Tnfsf10MouseTrail mediated signaling pathway   ISOTNFSF10 (Homo sapiens) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Bid  (BH3 interacting domain death agonist)
Casp3  (caspase 3)
Casp7  (caspase 7)
Casp8  (caspase 8)
Cflar  (CASP8 and FADD-like apoptosis regulator)
Fadd  (Fas associated via death domain)
Tnfrsf10b  (TNF receptor superfamily member 10b)
Tnfsf10  (TNF superfamily member 10)

Genes (Mus musculus)
Bid  (BH3 interacting domain death agonist)
Casp3  (caspase 3)
Casp7  (caspase 7)
Casp8  (caspase 8)
Cflar  (CASP8 and FADD-like apoptosis regulator)
Fadd  (Fas associated via death domain)
Tnfrsf10b  (tumor necrosis factor receptor superfamily, member 10b)
Tnfsf10  (tumor necrosis factor (ligand) superfamily, member 10)

Genes (Homo sapiens)
BID  (BH3 interacting domain death agonist)
CASP3  (caspase 3)
CASP7  (caspase 7)
CASP8  (caspase 8)
CFLAR  (CASP8 and FADD like apoptosis regulator)
FADD  (Fas associated via death domain)
TNFRSF10A  (TNF receptor superfamily member 10a)
TNFRSF10B  (TNF receptor superfamily member 10b)
TNFSF10  (TNF superfamily member 10)


Additional Information