ArticleThe Journal of biological chemistry2016
Distinct Activation Mechanisms of NF-κB Regulator Inhibitor of NF-κB Kinase (IKK) by Isoforms of the Cell Death Regulator Cellular FLICE-like Inhibitory Protein (cFLIP).
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- c-FLIP as a master regulator of immune homeostasis and disease mechanisms.Cell death & disease · 2026Review
- Review
- Gene Expression Regulation and the Signal Transduction of Programmed Cell Death.Current issues in molecular biology · 2024Review
- The mechanism of linear ubiquitination in regulating cell death and correlative diseases.Cell death & disease · 2023Review
- CRISPR screens identify novel regulators of cFLIP dependency and ligand-independent, TRAIL-R1-mediated cell death.Cell death and differentiation · 2023Article
- Regulation of apoptosis by ubiquitination in liver cancer.American journal of cancer research · 2023Review
- Primary and Secondary micro-RNA Modulation the Extrinsic Pathway of Apoptosis in Hepatocellular Carcinoma.Molecular biology · 2023Article
- Viral-mediated activation and inhibition of programmed cell death.PLoS pathogens · 2022Review
- Mechanistic insights into the activation of the IKK kinase complex by the Kaposi's sarcoma herpes virus oncoprotein vFLIP.The Journal of biological chemistry · 2022Article
- Interaction between the Hepatitis B Virus and Cellular FLIP Variants in Viral Replication and the Innate Immune System.Viruses · 2022Review
- The dual role of the CD95 and CD95L signaling pathway in glioblastoma.Frontiers in immunology · 2022Review
- Toll-like receptor 3 (TLR3) regulation mechanisms and roles in antiviral innate immune responses.Journal of Zhejiang University. Science. B · 2021Review
- Protein Kinase-Mediated Decision Between the Life and Death.Advances in experimental medicine and biology · 2021Article
- Cell-Penetrable Peptide-Conjugated FADD Induces Apoptosis and Regulates Inflammatory Signaling in Cancer Cells.International journal of molecular sciences · 2020Article
- Moonlighting Proteins Are Important Players in Cancer Immunology.Frontiers in immunology · 2020Review
- c-FLIP and CD95 signaling are essential for survival of renal cell carcinoma.Cell death & disease · 2019Article
- Delineating the role of c-FLIP/NEMO interaction in the CD95 network via rational design of molecular probes.BMC genomics · 2019Article
- cIAP1 promotes proliferation and migration and prevents apoptosis in gallbladder cancerBioscience reports · 2019Article
- Phytotherapies in inflammatory bowel disease.Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2019Review
- Cellular FLIP long isoform (cFLIPThe Journal of biological chemistry · 2018Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
The viral FLICE-like inhibitory protein (FLIP) protein from Kaposi sarcoma-associated herpesvirus activates the NF-κB pathway by forming a stable complex with a central region (amino acids 150-272) of the inhibitor of NF-κB kinase (IKK) γ subunits, thereby activating IKK. Cellular FLIP (cFLIP) forms are also known to activate the NF-κB pathway via IKK activation. Here we demonstrate that cFLIPL, cFLIPS, and their proteolytic product p22-FLIP all require the C-terminal region of NEMO/IKKγ (amino acids 272-419) and its ubiquitin binding function for activation of the IKK kinase (or kinase complex), but none form a stable complex with IKKγ. Our results further reveal that cFLIPLrequires the linear ubiquitin chain assembly complex and the kinase TAK1 for activation of the IKK kinase. Similarly, cFLIPSand p22-FLIP also require TAK1 but do not require LUBAC. In contrast, these isoforms are both components of complexes that incorporate Fas-associated death domain and RIP1, which appear essential for kinase activation. This conservation of IKK activation among the cFLIP family using different mechanisms suggests that the mechanism plays a critical role in their function.
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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.