ArticleCell death and differentiation2022
Proteasome inhibition triggers the formation of TRAIL receptor 2 platforms for caspase-8 activation that accumulate in the cytosol.
Article in Cell death and differentiation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Ligand-Engineered CuSmall (Weinheim an der Bergstrasse, Germany) · 2026Article
- Small molecule screening identifies cytotoxic endoplasmic reticulum-associated degradation inhibitors in multiple myeloma.Cell death & disease · 2026Article
- The Combination of Immunomodulatory Secretome and Liposome-Bound TRAIL Improves Knee Osteoarthritis Symptoms in an Ovine Model.Pharmaceutics · 2026Article
- Activation of the NLRP1B inflammasome by caspase-8.Communications biology · 2024Article
- Bortezomib promotes the TRAIL-mediated killing of resistant rhabdomyosarcoma by ErbB2/Her2-targeted CAR-NK-92 cells via DR5 upregulation.Molecular therapy. Oncology · 2024Article
- IRE1 RNase controls CD95-mediated cell death.EMBO reports · 2024Article
- Harnessing TRAIL-induced cell death for cancer therapy: a long walk with thrilling discoveries.Cell death and differentiation · 2023Review
- From Hair to Colon: Hair Follicle-Derived MSCs Alleviate Pyroptosis in DSS-Induced Ulcerative Colitis by Releasing Exosomes in a Paracrine Manner.Oxidative medicine and cellular longevity · 2022Article
- Endogenous Bok is stable at the endoplasmic reticulum membrane and does not mediate proteasome inhibitor-induced apoptosis.Frontiers in cell and developmental biology · 2022Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
Abstract
Cancer cells that are resistant to Bax/Bak-dependent intrinsic apoptosis can be eliminated by proteasome inhibition. Here, we show that proteasome inhibition induces the formation of high molecular weight platforms in the cytosol that serve to activate caspase-8. The activation complexes contain Fas-associated death domain (FADD) and receptor-interacting serine/threonine-protein kinase 1 (RIPK1). Furthermore, the complexes contain TRAIL-receptor 2 (TRAIL-R2) but not TRAIL-receptor 1 (TRAIL-R1). While RIPK1 inhibition or depletion did not affect proteasome inhibitor-induced cell death, TRAIL-R2 was found essential for efficient caspase-8 activation, since the loss of TRAIL-R2 expression abrogated caspase processing, significantly reduced cell death, and promoted cell re-growth after drug washout. Overall, our study provides novel insight into the mechanisms by which proteasome inhibition eliminates otherwise apoptosis-resistant cells, and highlights the crucial role of a ligand-independent but TRAIL-R2-dependent activation mechanism for caspase-8 in this scenario.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.