Palmitoylation of the TRAIL receptor DR4 confers an efficient TRAIL-induced cell death signalling.
S-palmitoylation is a lipid modification that regulates membrane-protein association and influences protein trafficking, stability or aggregation, thus playing an important role in protein signalling. We previously demonstrated that the palmitoylation of Fas, one of the DD (death domain)-containing members of the TNFR [TNF (tumour necrosis factor) receptor] superfamily, is essential for the redistribution of this receptor into lipid rafts, an obligatory step for the death signal transmission. Here we investigate the requirement of protein palmitoylation in the activities of other DD-containing death receptors. We show that DR4 is palmitoylated, whereas DR5 and TNFR1 are not. Furthermore, DR4 palmitoylation is required for its raft localization and its ability to oligomerize, two essential features in TRAIL (TNF-related apoptosis-inducing ligand)-induced death signal transmission.
Rossin
Aurélie
A
CNRS UMR 6543, Université de Nice Sophia-Antipolis, Institute of Developmental Biology and Cancer Research, Nice, France.
Derouet
Mathieu
M
Abdel-Sater
Fadi
F
Hueber
Anne-Odile
AO
D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D054878:Lipoylation / Q000502:physiology*; D055503:Protein Multimerization / Q000502:physiology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*
D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505653:TNFSF10 protein, human