title: Regulating the TRAIL of destruction: how A20 protects glioblastomas from TRAIL-mediated death.
abstract: In this issue of Cancer Discovery, Bellail and colleagues unravel how overexpression of the ubiquitin-modifying enzyme A20 results in TNF-related apoptosis-inducing ligand (TRAIL) resistance in glioblastoma. After TRAIL receptor stimulation, A20 mediates the polyubiquitination of RIP1 at the TRAIL receptor tail, resulting in the interaction of the polyubiquin chain to procaspase-8 that is recruited to the TRAIL-bound receptors. The inability of ubiquitin-bound procaspase-8 to be dimerized and activated prevents the execution of the apoptotic program.
authors.affiliation: Cancer Therapeutics Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Inge
authors.initials: I
authors.lastname: Verbrugge
authors.forename: Ricky W
authors.initials: RW
authors.lastname: Johnstone
mesh_terms: D001932:Brain Neoplasms / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D044767:Ubiquitin-Protein Ligases; C506249:RIPK1 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D053181:Caspase 8