ArticleCell death & disease2013
TNFα induces survival through the FLIP-L-dependent activation of the MAPK/ERK pathway.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 70 citations in OpenAlex.
- c-FLIP as a master regulator of immune homeostasis and disease mechanisms.Cell death & disease · 2026Review
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- Phosphorylation determines the glucose metabolism reprogramming and tumor-promoting activity of sine oculis homeobox 1.Signal transduction and targeted therapy · 2024Article
- Ellagic acid improves the symptoms of early-onset Alzheimer's disease: Behavioral and physiological correlates.Heliyon · 2024Article
- Gene expression networks regulated by human personality.Molecular psychiatry · 2024Review
- Cellular Dynamics of Fas-Associated Death Domain in the Regulation of Cancer and Inflammation.International journal of molecular sciences · 2024Review
- Microbiota as the unifying factor behind the hallmarks of cancer.Journal of cancer research and clinical oncology · 2023Review
- Tumor necrosis factor-α induces proliferation and reduces apoptosis of colorectal cancer cells through STAT3 activation.Immunogenetics · 2023Article
- The ERK5/NF-κB signaling pathway targets endometrial cancer proliferation and survival.Cellular and molecular life sciences : CMLS · 2022Article
- Potential Immune Indicators for Predicting the Prognosis of COVID-19 and Trauma: Similarities and Disparities.Frontiers in immunology · 2021Review
- Supramolecular Caffeic Acid and Bortezomib Nanomedicine: Prodrug Inducing Reactive Oxygen Species and Inhibiting Cancer Cell Survival.Pharmaceutics · 2020Article
- FLIP(L): the pseudo-caspase.The FEBS journal · 2020Review
- Dexmedetomidine-mediated regulation of miR-17-3p in H9C2 cells after hypoxia/reoxygenation injury.Experimental and therapeutic medicine · 2020Article
- Article
- Accelerated degradation of cFLIPScientific reports · 2019Article
- K27-linked ubiquitination of BRAF by ITCH engages cytokine response to maintain MEK-ERK signaling.Nature communications · 2019Article
- Pluronic micelles encapsulated curcumin manifests apoptotic cell death and inhibits pro-inflammatory cytokines in human breast adenocarcinoma cells.Cancer reports (Hoboken, N.J.) · 2019Article
- Topical Administration of a Soluble TNF Inhibitor Reduces Infarct Volume After Focal Cerebral Ischemia in Mice.Frontiers in neuroscience · 2019Article
- Macrophage Polarization: Different Gene Signatures in M1(LPS+) vs. Classically and M2(LPS-) vs. Alternatively Activated Macrophages.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of tumor necrosis factor receptor-1 can trigger survival or apoptosis pathways. In many cellular models, including the neuronal cell model PC12, it has been demonstrated that inhibition of protein synthesis is sufficient to render cells sensitive to apoptosis induced by TNFα. The survival effect is linked to the translocation of the transcription factor nuclear factor-kappa B (NF-κB) to the nucleus and activation of survival-related genes such as FLICE-like inhibitory protein long form (FLIP-L) or IAPs. Nonetheless, we previously reported an NF-κB-independent contribution of Bcl-xL to cell survival after TNFα treatment. Here, we demonstrate that NF-κB-induced increase in FLIP-L expression levels is essential for mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPK/ERK) activation. We demonstrate that FLIP-L behaves as a Raf-1 activator through both protein-protein interaction and Raf-1 kinase activation, without the requirement of the classical Ras activation. Importantly, prevention of FLIP-L increase by NF-κB inhibition or knockdown of endogenous FLIP-L blocks MAPK/ERK activation after TNFα treatment. From a functional point of view, we show that inhibition of the MAPK/ERK pathway and the NF-κB pathway are equally relevant to render PC12 cells sensitive to cell death induced by TNFα. Apoptosis induced by TNFα under these conditions is dependent on jun nuclear kinase1/2 JNK1/2-dependent Bim upregulation. Therefore, we report a previously undescribed and essential role for MAPK/ERK activation by FLIP-L in the decision between cell survival and apoptosis upon TNFα stimulation.
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