6533b830fe1ef96bd12970a9
RESEARCH PRODUCT
Differential inhibition of TRAIL-mediated DR5-DISC formation by decoy receptors 1 and 2.
Najoua LalaouiAlexandre MorizotMicheau OlivierDelphine MerinoEric SolaryPascal Schneidersubject
MESH : Hela CellsMESH: Membrane GlycoproteinsMESH: Membrane MicrodomainsDecoy Receptor 1ApoptosisMESH : Membrane GlycoproteinsReceptors Tumor Necrosis FactorTNF-Related Apoptosis-Inducing LigandMESH : TNF-Related Apoptosis-Inducing LigandJurkat Cells0302 clinical medicineMESH : Tumor Necrosis Factor Decoy ReceptorsMESH: Jurkat CellsDecoy receptorsReceptorCells CulturedMESH : Jurkat CellsMESH : Tumor Necrosis Factor-alpha0303 health sciencesMembrane GlycoproteinsMESH : Protein BindingArticlesMESH : Tumor Necrosis Factor Receptor-Associated Peptides and ProteinsTumor Necrosis Factor Receptor-Associated Peptides and ProteinsCell biology030220 oncology & carcinogenesisCaspasesDeath-inducing signaling complexApoptosis/drug effects; Apoptosis Regulatory Proteins/antagonists & inhibitors; Apoptosis Regulatory Proteins/pharmacology; Caspases/metabolism; Cells Cultured; Death Domain Receptor Signaling Adaptor Proteins; Enzyme Activation/drug effects; GPI-Linked Proteins; HeLa Cells; Humans; Jurkat Cells; Membrane Glycoproteins/antagonists & inhibitors; Membrane Glycoproteins/pharmacology; Membrane Microdomains/drug effects; Protein Binding/drug effects; Receptors TNF-Related Apoptosis-Inducing Ligand; Receptors Tumor Necrosis Factor/metabolism; TNF-Related Apoptosis-Inducing Ligand; Tumor Necrosis Factor Decoy Receptors; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/metabolism; Tumor Necrosis Factor-alpha/antagonists & inhibitors; Tumor Necrosis Factor-alpha/pharmacologyMESH : Apoptosis Regulatory ProteinsMESH: TNF-Related Apoptosis-Inducing LigandProtein BindingMESH: Cells CulturedDeath Domain Receptor Signaling Adaptor ProteinsMESH: Enzyme ActivationBiologyMESH: Tumor Necrosis Factor Receptor-Associated Peptides and ProteinsGPI-Linked Proteins03 medical and health sciencesMembrane MicrodomainsCell surface receptorMESH : Cells Cultured[SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular BiologyReceptors Tumor Necrosis Factor Member 10cHumansMESH: Protein Binding[SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular BiologyMESH: Receptors TNF-Related Apoptosis-Inducing LigandMESH : Receptors TNF-Related Apoptosis-Inducing LigandMolecular Biology[ SDV.BBM ] Life Sciences [q-bio]/Biochemistry Molecular Biology030304 developmental biologyDeath domainMESH: CaspasesMESH: HumansTumor Necrosis Factor-alphaMESH: Apoptosis Regulatory ProteinsMESH: ApoptosisMESH : HumansCell BiologyMESH: Receptors Tumor Necrosis FactorMESH: Tumor Necrosis Factor Decoy ReceptorsMESH : Receptors Tumor Necrosis FactorEnzyme ActivationMESH: Hela CellsReceptors TNF-Related Apoptosis-Inducing LigandTumor Necrosis Factor Decoy ReceptorsApoptosisMESH: Tumor Necrosis Factor-alphaMESH : Membrane MicrodomainsMESH : CaspasesApoptosis Regulatory ProteinsMESH : Enzyme ActivationMESH : ApoptosisMESH : Death Domain Receptor Signaling Adaptor ProteinsTumor Necrosis Factor Decoy ReceptorsHeLa CellsMESH: Death Domain Receptor Signaling Adaptor Proteinsdescription
International audience; Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family that induces cancer cell death by apoptosis with some selectivity. TRAIL-induced apoptosis is mediated by the transmembrane receptors death receptor 4 (DR4) (also known as TRAIL-R1) and DR5 (TRAIL-R2). TRAIL can also bind decoy receptor 1 (DcR1) (TRAIL-R3) and DcR2 (TRAIL-R4) that fail to induce apoptosis since they lack and have a truncated cytoplasmic death domain, respectively. In addition, DcR1 and DcR2 inhibit DR4- and DR5-mediated, TRAIL-induced apoptosis and we demonstrate here that this occurs through distinct mechanisms. While DcR1 prevents the assembly of the death-inducing signaling complex (DISC) by titrating TRAIL within lipid rafts, DcR2 is corecruited with DR5 within the DISC, where it inhibits initiator caspase activation. In addition, DcR2 prevents DR4 recruitment within the DR5 DISC. The specificity of DcR1- and DcR2-mediated TRAIL inhibition reveals an additional level of complexity for the regulation of TRAIL signaling.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2006-10-01 |