ArticleMolecular oncology2017
DR5-Cbl-b/c-Cbl-TRAF2 complex inhibits TRAIL-induced apoptosis by promoting TRAF2-mediated polyubiquitination of caspase-8 in gastric cancer cells.
Article in Molecular oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- LINC00324 induces nucleus pulposus cell apoptosis in intervertebral disc degeneration via miR-143-3p targeted TRAIL/DR4/DR5 axis.Biology direct · 2026Article
- E3 ubiquitin ligases orchestrate chemo-resistance in gastrointestinal malignancies: from DNA damage response to therapeutic targeting.Frontiers in oncology · 2026Review
- The Role of Post-Translational Modifications in Necroptosis.Biomolecules · 2025Review
- Review
- Review
- The role of CBL family ubiquitin ligases in cancer progression and therapeutic strategies.Frontiers in pharmacology · 2024Review
- The roles of E3 ubiquitin ligases in cancer progression and targeted therapy.Clinical and translational medicine · 2023Review
- Fn14 and TNFR2 as regulators of cytotoxic TNFR1 signaling.Frontiers in cell and developmental biology · 2023Review
- Regulation of apoptosis by ubiquitination in liver cancer.American journal of cancer research · 2023Review
- Review
- NR2F1-AS1/miR-190a/PHLDB2 Induces the Epithelial-Mesenchymal Transformation Process in Gastric Cancer by Promoting Phosphorylation of AKT3.Frontiers in cell and developmental biology · 2021Article
- High Level of Inflammatory Cytokines in the Tears: A Bridge of Patients with Concomitant Exotropia and Dry Eye.Oxidative medicine and cellular longevity · 2021Article
- Article
- Analysis of Gene Expression of miRNA-106b-5p andGenes · 2020Article
- Roles of TRAFs in Ischemia-Reperfusion Injury.Frontiers in cell and developmental biology · 2020Review
- PD-L1 Under Regulation of miR-429 Influences the Sensitivity of Gastric Cancer Cells to TRAIL by Binding of EGFR.Frontiers in oncology · 2020Article
- The E3 Ubiquitin Ligase Cbl-b Predicts Favorable Prognosis in Breast Cancer.Frontiers in oncology · 2020Article
- P-MAPA and IL-12 Differentially Regulate Proteins Associated with Ovarian Cancer Progression: A Proteomic Study.ACS omega · 2019Article
- E3 ubiquitin ligases and deubiquitinases as modulators of TRAIL-mediated extrinsic apoptotic signaling pathway.BMB reports · 2019Review
- Genetic Alterations of TRAF Proteins in Human Cancers.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ubiquitination of caspase-8 regulates TNF-related apoptosis-inducing ligand (TRAIL) sensitivity in cancer cells, and the preligand assembly complex plays a role in caspase-8 polyubiquitination. However, whether such a complex exists in gastric cancer cells and its role in TRAIL-triggered apoptosis is unclear. In this study, DR5, casitas B-lineage lymphoma-b (Cbl-b)/c-Cbl, and TRAF2 formed a complex in TRAIL-resistant gastric cancer cells, and Cbl-b and c-Cbl were the critical adaptors linking DR5 and TRAF2. Treatment with TRAIL induced caspase-8 translocation into the DR5-Cbl-b/c-Cbl-TRAF2 complex to interact with TRAF2, which then mediated the K48-linked polyubiquitination of caspase-8. The proteasome inhibitor bortezomib markedly enriched the p43/41 products of caspase-8 activated by TRAIL, indicating proteasomal degradation of caspase-8. Moreover, TRAF2 knockdown prevented the polyubiquitination of caspase-8 and thus increased TRAIL sensitivity. In addition, the inhibition of Cbl-b or c-Cbl expression and overexpression of miR-141 targeting Cbl-b and c-Cbl partially reversed TRAIL resistance by inhibiting the interaction between TRAF2 and caspase-8 and the subsequent polyubiquitination of caspase-8. These results indicate that the DR5-Cbl-b/c-Cbl-TRAF2 complex inhibited TRAIL-induced apoptosis by promoting TRAF2-mediated polyubiquitination of caspase-8 in gastric cancer cells.
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