A20 ubiquitin ligase-mediated polyubiquitination of RIP1 inhibits caspase-8 cleavage and TRAIL-induced apoptosis in glioblastoma.

ABSTRACT:

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The TNF-related apoptosis-inducing ligand (TRAIL) apoptotic pathway has emerged as a therapeutic target for the treatment of cancer. However, clinical trials have proven that the vast majority of human cancers are resistant to TRAIL apoptotic pathway-targeted therapies. We show that A20-mediated ubiquitination inhibits caspase-8 cleavage and TRAIL-induced apoptosis in glioblastoma through 2 signaling complexes. A20 is highly expressed in glioblastomas and, together with the death receptor 5 and receptor-interacting protein 1, forms a plasma membrane-bound preligand assembly complex under physiologic conditions. Treatment with TRAIL leads to the recruitment of caspase-8 to the plasma membrane-bound preligand assembly complex for the assembly of a death-inducing signaling

SUBMITTER: Bellail AC 

PROVIDER: S-EPMC3354650 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature