ArticleMolecular and cellular biology2013
Type I interferons induce apoptosis by balancing cFLIP and caspase-8 independent of death ligands.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Type I T cells sensitize treatment refractory tumors to chemotherapy through inhibition of oncogenic signaling pathways.Journal for immunotherapy of cancer · 2021Pooled it
- Striking the right balance with type I interferon signalling in cancer.Nature reviews. Cancer · 2026Review
- Concurrent TB and HIV therapies control TB reactivation during co-infection but not chronic immune activation.Nature communications · 2025Article
- Inhibition of IFNAR-JAK signaling enhances tolerability and transgene expression of systemic non-viral DNA delivery.Molecular therapy. Nucleic acids · 2025Article
- STING directly interacts with PAR to promote apoptosis upon acute ionizing radiation-mediated DNA damage.Cell death and differentiation · 2025Article
- The importance of IFNα2A (Roferon-A) in HSV-1 latency and T cell exhaustion in ocularly infected mice.PLoS pathogens · 2024Article
- c-FLIP facilitates ZIKV infection by mediating caspase-8/3-dependent apoptosis.PLoS pathogens · 2024Article
- NADeLife · 2024Article
- Emerging roles of plasmacytoid dendritic cell crosstalk in tumor immunity.Cancer biology & medicine · 2023Review
- Interferon alpha and beta receptor 1 knockout in human embryonic kidney 293 cells enhances the production efficiency of proteins or adenoviral vectors related to type I interferons.Frontiers in bioengineering and biotechnology · 2023Article
- SRSF6 balances mitochondrial-driven innate immune outcomes through alternative splicing of BAX.eLife · 2022Article
- Article
- STAT1 coordinates intestinal epithelial cell death during gastrointestinal infection upstream of Caspase-8.Mucosal immunology · 2022Article
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- SARS-CoV-2 suppresses IFNβ production mediated by NSP1, 5, 6, 15, ORF6 and ORF7b but does not suppress the effects of added interferon.PLoS pathogens · 2021Article
- Programmed Cell Death in the Small Intestine: Implications for the Pathogenesis of Celiac Disease.International journal of molecular sciences · 2021Review
- Oncolytic Viruses and Cancer, Do You Know the Main Mechanism?Frontiers in oncology · 2021Review
- COVID-19 and Parkinson's Disease: Shared Inflammatory Pathways Under Oxidative Stress.Brain sciences · 2020Article
- An alternative model for type I interferon induction downstream of human TLR2.The Journal of biological chemistry · 2020Article
- Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interferons induce a pleiotropy of responses through binding the same cell surface receptor. Here we investigated the molecular mechanism driving interferon-induced apoptosis. Using a nonbiased small interfering RNA (siRNA) screen, we show that silencing genes whose products are directly engaged in the initiation of interferon signaling completely abrogate the interferon antiproliferative response. Apoptosis-related genes such as the caspase-8, cFLIP, and DR5 genes specifically interfere with interferon-induced apoptosis, which we found to be independent of the activity of death ligands. The one gene for which silencing resulted in the strongest proapoptotic effect upon interferon signaling is the cFLIP gene, where silencing shortened the time of initiation of apoptosis from days to hours and increased dramatically the population of apoptotic cells. Thus, cFLIP serves as a regulator for interferon-induced apoptosis. A shift over time in the balance between cFLIP and caspase-8 results in downstream caspase activation and apoptosis. While gamma interferon (IFN-γ) also causes caspase-8 upregulation, we suggest that it follows a different path to apoptosis.
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