ArticleCellular signalling2015
TRAIL activates JNK and NF-κB through RIP1-dependent and -independent pathways.
Article in Cellular signalling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- The Fas-FasL system: from apoptosis regulator to therapeutic target in autoimmunity, cancer, and transplantation.Immunologic research · 2026Review
- Low extracellular pH enhances TRAIL-induced apoptosis by downregulating Mcl-1 expression.Experimental cell research · 2025Article
- Mcl-1 is a Gatekeeper Molecule to Regulate the Crosstalk Between Ferroptotic Agent-Induced ER Stress and TRAIL-Induced Apoptosis.Journal of cellular biochemistry · 2025Article
- Review
- Regulation of apoptosis by ubiquitination in liver cancer.American journal of cancer research · 2023Review
- Fn14 and TNFR2 as regulators of cytotoxic TNFR1 signaling.Frontiers in cell and developmental biology · 2023Review
- Induction of Breast Cancer Cell Apoptosis by TRAIL and Smac Mimetics: Involvement of RIP1 and cFLIP.Current issues in molecular biology · 2022Article
- Microglial cathepsin E plays a role in neuroinflammation and amyloid β production in Alzheimer's disease.Aging cell · 2022Article
- The dual role of the CD95 and CD95L signaling pathway in glioblastoma.Frontiers in immunology · 2022Review
- The long road to TRAIL therapy: a TRAILshort detour.Oncotarget · 2021Article
- The lncRNA CASC2 Modulates Hepatocellular Carcinoma Cell Sensitivity and Resistance to TRAIL Through Apoptotic and Non-Apoptotic Signaling.Frontiers in oncology · 2021Article
- Functional roles in cell signaling of adaptor protein TRADD from a structural perspective.Computational and structural biotechnology journal · 2020Review
- Glucosamine Enhances TRAIL-Induced Apoptosis in the Prostate Cancer Cell Line DU145.Medicines (Basel, Switzerland) · 2019Article
- Article
- TAK1 inhibition subverts the osteoclastogenic action of TRAIL while potentiating its antimyeloma effects.Blood advances · 2017Article
- The linear ubiquitin chain assembly complex regulates TRAIL-induced gene activation and cell death.The EMBO journal · 2017Article
- Icariside II overcomes TRAIL resistance of melanoma cells through ROS-mediated downregulation of STAT3/cFLIP signaling.Oncotarget · 2016Article
- Lipid-Induced Signaling Causes Release of Inflammatory Extracellular Vesicles From Hepatocytes.Gastroenterology · 2016Article
- Marine Drugs Regulating Apoptosis Induced by Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL).Marine drugs · 2015Review
- SMAC mimetic Debio 1143 synergizes with taxanes, topoisomerase inhibitors and bromodomain inhibitors to impede growth of lung adenocarcinoma cells.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The death receptor (DR) ligand TRAIL is being evaluated in clinical trials as an anti-cancer agent; however, many studies have found that TRAIL also enhances tumor progression by activating the NF-κB pathway in apoptosis-resistant cells. Although RIP1, cFLIP and caspase-8 have been implicated in TRAIL-induced JNK and NF-κB activation, underlying mechanisms are unclear. By examining the kinetics of pathway activation in TRAIL-sensitive lymphoma cells wild-type or deficient for RIP1, TRAF2, cIAP1/2 or HOIP, we report here that TRAIL induces two phases of JNK and NF-κB activation. The early phase is activated by TRAF2- and cIAP1-mediated ubiquitination of RIP1, whereas the delayed phase is induced by caspase-dependent activation of MEKK1 independent of RIP1 and TRAF2 expression. cFLIP overexpression promotes the early phase but completely suppresses the delayed phase of pathway activation in lymphoma cells, whereas Bcl-2 overexpression promotes both the early and delayed phases of the pathways. In addition, stable overexpression of cFLIP in RIP1- or TRAF2-deficient cells confers resistance to apoptosis, but fails to mediate NF-κB activation. HOIP is not essential for, but contributes to, TRAIL-induced NF-κB activation in cFLIP-overexpressing cells. These findings not only elucidate details of the mechanisms underlying TRAIL-induced JNK and NF-κB activation, but also clarify conflicting reports in the field.
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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.