ArticleThe Journal of cell biology2015
Reversible ubiquitination shapes NLRC5 function and modulates NF-κB activation switch.
Article in The Journal of cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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34 citing papers in PubMed, 53 citations in OpenAlex.
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- Targeting pattern recognition receptors for cancer therapy: Mechanisms and strategies.Acta pharmaceutica Sinica. B · 2025Review
- New insights into the structure domain and function of NLR family CARD domain containing 5.Cell communication and signaling : CCS · 2025Review
- DSCI: a database of synthetic biology components for innate immunity and cell engineering decision-making processes.Advanced biotechnology · 2024Article
- HIV-Associated Neurocognitive Disorder: A Look into Cellular and Molecular Pathology.International journal of molecular sciences · 2024Review
- NLRC5 Deficiency Reduces LPS-Induced Microglial Activation via Inhibition of NF-κB Signaling and Ameliorates Mice's Depressive-like Behavior.International journal of molecular sciences · 2023Article
- Ubiquitin-specific peptidases: Players in bone metabolism.Cell proliferation · 2023Review
- NLRC5 restricts dengue virus infection by promoting the autophagic degradation of viral NS3 through E3 ligase CUL2 (cullin 2).Autophagy · 2023Article
- Ubiquitin-Specific Proteases (USPs) and Metabolic Disorders.International journal of molecular sciences · 2023Review
- USP14 promotes tryptophan metabolism and immune suppression by stabilizing IDO1 in colorectal cancer.Nature communications · 2022Article
- K63 ubiquitination in immune signaling.Trends in immunology · 2022Review
- Toll-Like Receptor Signaling and Its Role in Cell-Mediated Immunity.Frontiers in immunology · 2022Review
- Advances in the Development Ubiquitin-Specific Peptidase (USP) Inhibitors.International journal of molecular sciences · 2021Review
- Classical MHC expression by DP thymocytes impairs the selection of non-classical MHC restricted innate-like T cells.Nature communications · 2021Article
- The MHC Class-I Transactivator NLRC5: Implications to Cancer Immunology and Potential Applications to Cancer Immunotherapy.International journal of molecular sciences · 2021Review
- NLRC5 Deficiency Deregulates Hepatic Inflammatory Response but Does Not Aggravate Carbon Tetrachloride-Induced Liver Fibrosis.Frontiers in immunology · 2021Article
- The subcellular redistribution of NLRC5 promotes angiogenesis via interacting with STAT3 in endothelial cells.Theranostics · 2021Article
- The Regulatory NOD-Like Receptor NLRC5 Promotes Ganglion Cell Death in Ischemic Retinopathy by Inducing Microglial Pyroptosis.Frontiers in cell and developmental biology · 2021Article
- Toll-like receptors in sepsis-associated cytokine storm and their endogenous negative regulators as future immunomodulatory targets.International immunopharmacology · 2020Review
- A mathematic model to reveal delicate cross-regulation between MAVS/STING, inflammasome and MyD88-dependent type I interferon signalling.Journal of cellular and molecular medicine · 2020Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NLRC5 is an important regulator in innate immune responses. However, the ability of NLRC5 to inhibit NF-κB activation is controversial in different cell types. How dynamic modification of NLRC5 shapes NF-κB signaling remains unknown. We demonstrated that NLRC5 undergoes robust ubiquitination by TRAF2/6 after lipopolysaccharide treatment, which leads to dissociation of the NLRC5-IκB kinase complex. Experimental and mathematical analyses revealed that the K63-linked ubiquitination of NLRC5 at lysine 1,178 generates a coherent feedforward loop to further sensitize NF-κB activation. Meanwhile, we found USP14 specifically removes the polyubiquitin chains from NLRC5 to enhance NLRC5-mediated inhibition of NF-κB signaling. Furthermore, we found that different cell types may exhibit different sensitivities to NF-κB activation in response to NLRC5 ablation, possibly as a result of the various intrinsic levels of deubiquitinases and NLRC5. This might partially reconcile controversial studies and explain why NLRC5 exhibits diverse inhibitory efficiencies. Collectively, our results provide the regulatory mechanisms of reversible NLRC5 ubiquitination and its role in the dynamic control of innate immunity.
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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.