Affinage

NLRC5

Protein NLRC5 · UniProt Q86WI3

Length
1866 aa
Mass
204.6 kDa
Annotated
2026-04-29
100 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NLRC5 is a multifunctional NLR family member that serves as the master transcriptional co-activator (CITA) of MHC class I genes and modulates innate immune signaling and inflammatory cell death. NLRC5 is recruited to SXY enhancer motifs on MHC-I, β2-microglobulin, TAP1, LMP2, and BTN3A promoters through obligate interaction with the RFX5-containing enhanceosome complex, driving coordinated antigen presentation gene expression in an IFN-γ-inducible, karyopherin- and NBD/NLS-dependent manner (PMID:20639463, PMID:25811463, PMID:22412192, PMID:33364588). In the cytoplasm, NLRC5 inhibits NF-κB signaling by directly binding IKKα/IKKβ and blocking their phosphorylation, with this inhibitory activity dynamically tuned by TRAF2/6-mediated K63-ubiquitination at K1178 and USP14-mediated deubiquitination (PMID:20434986, PMID:26620909, PMID:36372300). NLRC5 also functions as an innate sensor of NAD+ depletion and specific PAMPs, assembling NLRP12-containing PANoptosome complexes to drive inflammatory cell death, and interacts with RIG-I via its atypical CARD to modulate antiviral interferon responses (PMID:38878777, PMID:20434986, PMID:25404059).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2010 High

    The first functional characterization of NLRC5 established two cytoplasmic signaling roles — inhibition of NF-κB via direct IKKα/β binding and suppression of RLR-mediated type I IFN responses via RIG-I/MDA5 interaction — revealing it as a negative regulator of innate immune signaling.

    Evidence Co-immunoprecipitation, phosphorylation assays, and siRNA knockdown with reporter assays in multiple cell types

    PMID:20434986

    Open questions at the time
    • Structural basis for IKK interaction unknown
    • Relative importance of NF-κB vs IFN inhibition in vivo not resolved
    • Endogenous stoichiometry of NLRC5-IKK complex not measured
  2. 2010 High

    Concurrent studies identified NLRC5 as a transcriptional co-activator (CITA) of MHC class I genes, fundamentally redefining NLRC5 from a purely cytoplasmic sensor to a nucleo-cytoplasmic shuttling transcriptional regulator that occupies MHC-I promoters and drives coordinated expression of antigen presentation machinery.

    Evidence ChIP on MHC-I promoters, reporter assays, siRNA knockdown, subcellular fractionation in lymphoid and epithelial lines

    PMID:20610642 PMID:20639463

    Open questions at the time
    • How NLRC5 is recruited to MHC-I promoters (cis-element specificity) not yet defined
    • Whether NLRC5 acts independently or through co-factors unknown
  3. 2012 High

    Generation of NLRC5-knockout mice validated NLRC5 as the dominant, non-redundant transactivator of MHC class I in lymphocytes, showing that its loss profoundly impairs MHC-I expression, CD8+ T cell priming, and Listeria clearance, while its contribution to NF-κB and type I IFN suppression was confirmed by enhanced IKK/IRF3 phosphorylation in KO macrophages.

    Evidence Multiple independent NLRC5-KO mouse lines, flow cytometry, bacterial infection, CD8+ T cell assays, cytokine/phosphorylation measurements

    PMID:22412192 PMID:22473004 PMID:22491475 PMID:22711889

    Open questions at the time
    • Residual MHC-I expression in APCs implies compensatory mechanisms (likely CIITA) not fully delineated
    • Whether NLRC5 inflammasome role is physiologically relevant was disputed by KO studies
  4. 2012 Medium

    Domain mutagenesis established that the NBD is required for nuclear translocation and the NLS is essential for MHC-I transactivation, linking ATP-binding to the nuclear import mechanism.

    Evidence NBD and NLS mutants assessed by reporter assays and localization studies

    PMID:22310711

    Open questions at the time
    • Whether NBD hydrolysis or just binding is required not distinguished
    • Direct NLS–karyopherin interaction not biochemically mapped
  5. 2014 High

    Structural determination of the NLRC5 N-terminal domain revealed an atypical CARD (six α-helix death fold) with a modified electrostatic surface, explaining how it engages RIG-I tandem CARDs and contributes to antiviral signaling.

    Evidence Solution NMR structure plus in vitro pulldown with RIG-I CARDs

    PMID:24815518 PMID:25404059

    Open questions at the time
    • Full-length NLRC5 structure unavailable
    • How atypical CARD engages enhanceosome or IKK not resolved
  6. 2015 High

    ChIP-seq and genetic epistasis defined the mechanism of NLRC5 promoter specificity: NLRC5 is recruited exclusively to SXY enhancer modules via the RFX5 enhanceosome, with the S-box distinguishing NLRC5-dependent MHC-I from CIITA-dependent MHC-II promoters.

    Evidence ChIP-seq, Rfx5-KO and Nlrc5/CIIta double-KO mice, de novo motif analysis, reporter assays in RFX-deficient B cells

    PMID:25811463

    Open questions at the time
    • Precise protein–protein contacts between NLRC5 and RFX5 not structurally resolved
    • How atypical CARD contributes to enhanceosome assembly unknown
  7. 2015 High

    A post-translational regulatory circuit was elucidated: TRAF2/6-mediated K63-ubiquitination at K1178 releases NLRC5 from IKK, creating a feedforward loop that sensitizes NF-κB, while USP14 deubiquitinates NLRC5 to restore inhibition — establishing dynamic control of NLRC5's NF-κB-suppressive function.

    Evidence Site-directed mutagenesis (K1178), ubiquitination assays, USP14 identification, mathematical modeling

    PMID:26620909

    Open questions at the time
    • Whether K63-ubiquitination also affects nuclear import or MHC-I transactivation not tested
    • Other E3 ligases or DUBs that regulate NLRC5 not excluded
  8. 2016 High

    Conditional T-cell-specific NLRC5 deletion revealed the physiological consequence of NLRC5-driven MHC-I: protection of T cells from NK-cell-mediated killing during inflammation and chronic viral infection, establishing NLRC5 as essential for self-tolerance maintenance.

    Evidence T-cell-specific Nlrc5-KO mice, NK depletion rescue, LCMV infection model

    PMID:26861112

    Open questions at the time
    • Whether NK licensing is altered by NLRC5 deficiency not addressed
    • Contribution of non-classical MHC-I ligands not separated
  9. 2020 Medium

    The transcriptional target repertoire of NLRC5 was expanded beyond classical MHC-I to include BTN3A1-3 butyrophilin genes, linking NLRC5 to γδ T cell-mediated tumor surveillance, and upstream regulation by PRMT5-mediated transcriptional repression of NLRC5 itself was identified.

    Evidence ChIP and reporter assays for BTN3A promoters; PRMT5 knockdown/inhibition with MHC-I and tumor model readouts

    PMID:32641491 PMID:33364588

    Open questions at the time
    • Whether NLRC5 uses the same SXY/RFX5 mechanism for BTN3A not fully defined
    • PRMT5 mechanism (direct histone methylation vs indirect) at NLRC5 locus not resolved
  10. 2021 High

    SARS-CoV-2 ORF6 was shown to suppress NLRC5 at two levels — blocking STAT1-dependent transcription of NLRC5 and inhibiting karyopherin-mediated nuclear import — revealing a viral immune evasion strategy targeting MHC-I transactivation.

    Evidence ORF6 overexpression, nuclear import assays, STAT1 signaling analysis, COVID-19 patient expression data

    PMID:34782627

    Open questions at the time
    • Whether other coronaviruses use the same mechanism unknown
    • Impact on patient CD8+ T cell responses not directly measured
  11. 2022 Medium

    Post-transcriptional regulation of NLRC5 was characterized: m6A modification of NLRC5 mRNA by METTL3 stabilizes it against YTHDF2-mediated decay, and LC3 directly binds NLRC5 protein to inhibit its MHC-I transactivation, adding epitranscriptomic and autophagic layers of control.

    Evidence RNA immunoprecipitation, methylated RIP, RNA stability assays, LC3-NLRC5 Co-IP with in vivo tumor models

    PMID:34974132 PMID:37085864

    Open questions at the time
    • Whether LC3 sequesters NLRC5 in the cytoplasm or promotes its degradation not distinguished
    • m6A regulation in non-cancer contexts not examined
  12. 2022 Medium

    A new cytoplasmic effector function was identified: NLRC5 recruits the E3 ligase CUL2 to catalyze K48-ubiquitination of dengue virus NS3, targeting it for TOLLIP-mediated selective autophagic degradation, linking NLRC5 to antiviral autophagy independent of its transcriptional role.

    Evidence Co-IP, ubiquitination assays, autophagy pathway analysis, NLRC5 KO/OE with viral replication readouts

    PMID:36126167

    Open questions at the time
    • Whether this autophagy-targeting function extends to other viral proteins unknown
    • Structural basis for NS3 recognition not defined
    • Single-lab finding awaits independent confirmation
  13. 2024 High

    NLRC5 was identified as an innate sensor of NAD+ depletion that assembles with NLRP12 and PANoptosome components to drive PANoptosis (combined pyroptosis, apoptosis, and necroptosis), establishing a cell death function distinct from its transcriptional and NF-κB-inhibitory roles.

    Evidence PANoptosis screening, Co-IP with NLRP12 and cell death effectors, NLRC5-KO mice in hemolytic and inflammatory models, ROS measurements

    PMID:38878777

    Open questions at the time
    • How NLRC5 senses NAD+ depletion (direct binding vs indirect) not determined
    • Structural basis of NLRC5-NLRP12 interaction unknown
    • Whether PANoptosome function is active in non-myeloid cells not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include: (1) the structural basis for NLRC5 engagement with the RFX5 enhanceosome versus cytoplasmic signaling partners, (2) how the transcriptional, NF-κB-inhibitory, and PANoptosome functions are partitioned across cell types and stimuli, and (3) whether a unifying activation mechanism (nucleotide binding/hydrolysis) controls toggling between nuclear and cytoplasmic functions.
  • No full-length NLRC5 structure exists
  • Relative contribution of each function in specific disease contexts not quantified
  • Allosteric regulation by nucleotide binding/hydrolysis not mechanistically dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0098772 molecular function regulator activity 5
Localization
GO:0005634 nucleus 5 GO:0005829 cytosol 4
Pathway
R-HSA-168256 Immune System 10 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 1
Partners
HSPA8IKKΑIKKΒNLRP12RFX5RIG-ITRAF2USP14
Complex memberships
NLRC5-IKKα/β inhibitory complexNLRC5-NLRP12 PANoptosomeRFX5/RFXAP/RFXANK enhanceosome

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 NLRC5 inhibits NF-κB-dependent responses by directly interacting with IKKα and IKKβ and blocking their phosphorylation, and also interacts with RIG-I and MDA5 (but not MAVS) to inhibit RLR-mediated type I interferon responses. Co-immunoprecipitation, siRNA knockdown with NF-κB/IFN reporter assays, phosphorylation assays Cell High 20434986
2010 NLRC5 is an IFN-γ-inducible nuclear protein that acts as a transcriptional regulator (class I transactivator, CITA) of MHC class I genes; it associates with MHC class I gene promoters and is required for IFN-γ-induced upregulation of MHC class I, β2-microglobulin, TAP1, and LMP2. Chromatin immunoprecipitation (ChIP), reporter gene assays, siRNA knockdown, overexpression in lymphoid and epithelial cell lines Proceedings of the National Academy of Sciences of the United States of America High 20639463
2010 NLRC5 shuttles between the cytosol and the nucleus in a CrmA-dependent manner, and overexpression globally dampens NF-κB-, AP-1-, and type I IFN-dependent signaling, most likely through transcriptional repression. Subcellular fractionation/localization, overexpression in HEK293T cells, reporter assays, siRNA knockdown in RAW264.7 macrophages Journal of immunology Medium 20610642
2010 NLRC5 forms an inflammasome complex: it biochemically associates with NLRP3 in a nucleotide-binding domain-dependent but LRR-inhibitory fashion, and together with procaspase-1, pro-IL-1β, and ASC reconstitutes inflammasome activity cooperative with NLRP3; RNAi knockdown nearly eliminated caspase-1, IL-1β, and IL-18 processing. Co-immunoprecipitation, reconstitution assay, siRNA knockdown in primary human monocytic cells Journal of immunology Medium 21191067
2010 Overexpression and enforced oligomerization of NLRC5 activates IFN-γ activation sequence (GAS) and IFN-specific response element (ISRE) promoter elements and upregulates antiviral target genes; JAK/STAT-mediated autocrine IFN-γ signaling loop is involved in NLRC5 upregulation post-CMV infection. Reporter gene assays (GAS/ISRE), siRNA knockdown, overexpression with forced oligomerization Journal of immunology Medium 20061403
2012 NLRC5 deficiency in mice results in a profound defect specifically in MHC class I expression (and related genes β2M, TAP1, LMP2) in T, NKT, and NK lymphocytes but only mildly affects APCs; endogenous NLRC5 localizes to the nucleus and occupies proximal promoter regions of H-2 genes; MHC class I induction requires both CARD and LRR domains. Nlrc5-knockout mouse generation, flow cytometry, nuclear fractionation, ChIP Journal of immunology High 22412192
2012 In NLRC5-deficient mice, MHC class I expression and genes essential for antigen presentation (H-2K, H-2D, β2M, TAP1, LMP2) are severely reduced; IFN-γ stimulation cannot overcome this defect; Listeria-specific CD8+ T cell responses are impaired and bacterial clearance is reduced. NLRC5 knockout mouse, flow cytometry, bacterial infection model, CD8+ T cell functional assays Journal of immunology High 22711889
2012 NLRC5-deficient mice show enhanced IKK and IRF3 phosphorylation and increased IL-6 and IFN-β production in response to TLR stimulation or VSV infection; NLRC5 expression induction by TLR ligands or cytokines requires STAT1-mediated signaling. NLRC5 knockout mouse, phosphorylation assays (IKK, IRF3), ELISA for cytokines, STAT1 pathway analysis Cell research High 22473004
2012 NLRC5 is required for MHC class I-mediated antigen presentation in vivo; NLRC5-deficient mice show profound defect in MHC class I gene expression, fail to activate Listeria-specific CD8+ T cell responses, and show partial impairment of NLRP3-mediated inflammasome activation, but NLRC5 is dispensable for NF-κB-dependent pro-inflammatory gene expression and type I IFN genes. NLRC5 knockout mouse, flow cytometry, CD8+ T cell activation/proliferation/cytotoxicity assays, bacterial infection Cell research High 22491475
2012 The nucleotide-binding domain (NBD) of NLRC5 is critical for both nuclear translocation and transactivation of MHC class I genes; intact nuclear localization signal is required for NLRC5-mediated MHC class I gene induction. NBD domain mutants, nuclear localization signal mutagenesis, reporter gene assays, cellular localization studies Biochemical and biophysical research communications Medium 22310711
2014 The N-terminal effector domain of NLRC5 adopts a six α-helix bundle with a general death fold (atypical CARD), structurally distinct from canonical CARD; in vitro interaction experiments with the tandem CARD of RIG-I were performed; the atypical features affect the electrostatic surface and likely modulate CARD-CARD interactions. Solution NMR structure determination, in vitro pulldown/interaction experiments Biochemistry High 24815518
2014 NLRC5 binds RIG-I via its N-terminal death domain; this interaction is critical for robust antiviral responses against influenza virus; NLRC5 extends and stabilizes influenza virus-induced RIG-I expression; influenza NS1 protein binds NLRC5 to suppress its function; antiviral activity is LRR domain-independent. Co-immunoprecipitation, domain mapping, overexpression/knockdown in A549 and primary bronchial cells, viral replication assays European journal of immunology Medium 25404059
2015 NLRC5 exclusively transactivates MHC class I and related non-classical MHCI genes through an SXY enhancer module; recruitment of NLRC5 to MHC class I promoters absolutely requires the enhanceosome factor RFX5; NLRC5 and CIITA occupy distinct SXY motifs with the S box being the key determinant of NLRC5 specificity; Rfx5-knockout mice phenocopy Nlrc5 deficiency for MHCI expression. ChIP-sequencing, Rfx5-knockout mice, double-deficient Nlrc5/CIIta mice, de novo motif discovery, reporter assays in B cell lines lacking RFX5/RFXAP/RFXANK PLoS genetics High 25811463
2015 NLRC5 undergoes K63-linked ubiquitination at lysine 1178 by TRAF2/6 after LPS treatment, which leads to dissociation of the NLRC5-IκB kinase complex and creates a coherent feedforward loop to sensitize NF-κB activation; USP14 specifically removes polyubiquitin chains from NLRC5 to restore NLRC5-mediated inhibition of NF-κB signaling. Ubiquitination assay, site-directed mutagenesis (K1178), Co-IP, mathematical modeling, USP14 deubiquitinase identification The Journal of cell biology High 26620909
2016 NLRC5 shields T lymphocytes from NK-cell-mediated killing under inflammatory conditions by maintaining high MHCI expression; T-cell-specific Nlrc5-deficient mice show NK cells breaking tolerance toward self Nlrc5-deficient T cells under inflammation; during chronic LCMV infection, total CD8+ T cell population is severely decreased in a NK-cell-dependent manner. T-cell-specific Nlrc5-knockout mice, NK cell depletion, LCMV infection model, flow cytometry Nature communications High 26861112
2021 SARS-CoV-2 ORF6 protein suppresses NLRC5 both transcriptionally (by hampering IFN-γ-mediated STAT1 signaling, reducing NLRC5 and IRF1 gene expression) and functionally (by blocking karyopherin complex-dependent nuclear import of NLRC5), thereby inhibiting MHC class I pathway induction. Gene expression profiling of COVID-19 patients and infected cell lines, ORF6 overexpression, nuclear import assays, STAT1 signaling analysis Nature communications High 34782627
2020 NLRC5 promotes transcription of BTN3A1-3 genes through an atypical regulatory motif in their promoters; forcing NLRC5 expression promotes Vγ9Vδ2 T-cell-mediated killing of tumor cells in a BTN3A-dependent manner. ChIP, reporter assays, NLRC5 overexpression, co-culture killing assays with BTN3A neutralization iScience Medium 33364588
2022 NLRC5 interacts with dengue virus NS3 protease domain and mediates its degradation through a ubiquitin-dependent selective autophagy pathway; NLRC5 recruits E3 ubiquitin ligase CUL2 to catalyze K48-linked poly-ubiquitination of NS3, which serves as a recognition signal for TOLLIP-mediated selective autophagic degradation. Co-immunoprecipitation, ubiquitination assays, autophagy pathway analysis, NLRC5 knockout/overexpression, viral replication assays Autophagy Medium 36126167
2024 NLRC5 acts as an innate immune sensor for NAD+ depletion and specific PAMP/heme and heme/cytokine combinations to drive PANoptosis (inflammatory cell death); NLRC5 interacts with NLRP12 and PANoptosome components to form a multi-protein cell death complex; TLR signaling and NAD+ levels regulate NLRC5 expression and ROS production to control cell death; NLRC5-deficient mice are protected in hemolytic and inflammatory models. PANoptosis screening, Co-immunoprecipitation with NLRP12 and PANoptosome components, NLRC5-deficient mice, cell death assays, ROS measurement Cell High 38878777
2022 In human pancreatic β cells, NLRC5 is induced by IFNα and regulates HLA class I expression, antigen presentation-related genes, chemokines, and mediates IFNα effects on alternative splicing that generates neoantigens. Bulk and single-cell RNA sequencing, NLRC5 knockdown in EndoC-βH1 and human islet cells, targeted gene/protein determination Science advances Medium 36103539
2020 PRMT5 inhibits transcription of the NLRC5 gene; PRMT5 knockdown augments NLRC5 expression and increases MHC class I abundance in melanoma cells; combining PRMT5 inhibition with immune checkpoint therapy enhanced antitumor efficacy. PRMT5 knockdown/inhibition, gene expression analysis, MHC-I flow cytometry, in vivo tumor models Science translational medicine Medium 32641491
2021 Autophagy protein LC3 directly interacts with NLRC5 and inhibits NLRC5-mediated MHC class I antigen presentation pathway in vitro and in vivo; negative correlation between NLRC5 and LC3 levels was found in endometrial cancer. Co-immunoprecipitation (LC3-NLRC5), overexpression/knockdown, in vivo tumor model, MHC-I expression assays Cancer letters Medium 34974132
2023 METTL3 facilitates m6A modification of NLRC5 mRNA; YTHDF2 promotes degradation of NLRC5 mRNA; METTL3 inhibits NLRC5 mRNA degradation through a YTHDF2-dependent mechanism, thereby promoting MHC-I-mediated immunosurveillance in endometrial cancer. RNA immunoprecipitation (RIP), methylated RIP, RNA stability assays, METTL3/YTHDF2 overexpression/depletion, in vivo tumor model Biomarker research Medium 37085864
2022 USP14 deubiquitinase directly interacts with NLRC5 and suppresses its degradation, thereby upregulating NLRC5-mediated inhibition of NF-κB signaling in endothelial cells to restrain atherosclerosis progression. Co-immunoprecipitation, ubiquitination assay, USP14 overexpression/knockdown, in vivo ApoE-/- mouse model Biochimica et biophysica acta. Molecular and cell biology of lipids Medium 36372300
2023 USP14 promotes deubiquitination and upregulation of NLRC5, with subsequent Smad2/3 pathway activation to drive endothelial-to-mesenchymal transformation (EndMT) in atherosclerosis; USF1 transcriptionally activates USP14, forming a USF1/USP14/NLRC5 axis. Dual-luciferase reporter assay, ChIP, Co-IP, USF1/USP14/NLRC5 knockdown/overexpression, in vivo ApoE-/- mouse model Molecular medicine Medium 38424494
2023 NLRC5 deficiency in macrophages decreases NF-κB pathway activation and reduces secretion of IL-6; mechanistically, NLRC5 interacts with HSPA8 (heat shock cognate protein 70) to suppress NF-κB signaling; myeloid-specific NLRC5 deletion aggravates pressure overload-induced cardiac remodeling. Myeloid-specific NLRC5 knockout mice, Co-immunoprecipitation (NLRC5-HSPA8), NF-κB signaling assays, cytokine measurement, cardiac remodeling model JACC. Basic to translational science Medium 37325412
2019 In HIV-1 Tat-exposed microglia, miRNA-34a is upregulated and directly targets NLRC5 mRNA (identified by bioinformatics and Argonaute immunoprecipitation); downregulation of NLRC5 by miR-34a leads to increased NF-κB p65 expression and microglial inflammation. Argonaute immunoprecipitation, miR-34a mimic/inhibitor transfection, NF-κB expression assays, validated in HIV-1 transgenic rat and SIV-infected macaque brain Brain, behavior, and immunity Medium 30872089
2021 NLRC5 deficiency in macrophages (myeloid-specific knockout) leads to higher chemokine and cytokine production in response to Helicobacter and promotes B-cell activating factor-driven B-cell hyperproliferation and gastric lymphoid tissue formation. Myeloid-specific Nlrc5-KO mice (Nlrc5mø-KO), CRISPR-Cas9 NLRC5-/- THP-1 cells, H. felis infection model, cytokine assays, histology Gastroenterology Medium 32169428
2021 NLRC5 deficiency reduces dopaminergic neurodegeneration in MPTP-induced Parkinson's disease model; NLRC5 deficiency decreased proinflammatory gene expression in microglia and astrocytes by suppressing NF-κB and MAPK signaling pathways and enhancing AKT-GSK-3β and AMPK signaling; in neurons, NLRC5 deficiency promoted NF-κB and AKT signaling and increased survival. NLRC5-deficient mice, MPTP model, primary microglia/astrocyte cultures, NF-κB/MAPK/AKT signaling assays, dopaminergic neuron counting Journal of neuroinflammation Medium 37072793
2021 In ischemic retinopathy, NLRC5 directly binds NLRP3 and NLRC4 in inflammasomes to cooperatively drive microglial pyroptosis and apoptosis; NLRC5 knockdown markedly suppressed gasdermin D (GSDMD) cleavage and activation of IL-1β and caspase-3. Co-immunoprecipitation (NLRC5-NLRP3, NLRC5-NLRC4), NLRC5 knockdown in retinal microglia, GSDMD cleavage assay, retinal ischemia-reperfusion model Frontiers in cell and developmental biology Medium 34095138

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways. Cell 372 20434986
2010 NLR family member NLRC5 is a transcriptional regulator of MHC class I genes. Proceedings of the National Academy of Sciences of the United States of America 359 20639463
2012 NLRC5: a key regulator of MHC class I-dependent immune responses. Nature reviews. Immunology 306 23175229
2016 NLRC5/MHC class I transactivator is a target for immune evasion in cancer. Proceedings of the National Academy of Sciences of the United States of America 222 27162338
2010 NLRC5 limits the activation of inflammatory pathways. Journal of immunology (Baltimore, Md. : 1950) 201 20610642
2020 PRMT5 control of cGAS/STING and NLRC5 pathways defines melanoma response to antitumor immunity. Science translational medicine 194 32641491
2010 Cutting edge: NLRC5-dependent activation of the inflammasome. Journal of immunology (Baltimore, Md. : 1950) 179 21191067
2010 The nucleotide-binding oligomerization domain-like receptor NLRC5 is involved in IFN-dependent antiviral immune responses. Journal of immunology (Baltimore, Md. : 1950) 173 20061403
2010 A role for the human nucleotide-binding domain, leucine-rich repeat-containing family member NLRC5 in antiviral responses. The Journal of biological chemistry 145 20538593
2024 NLRC5 senses NAD+ depletion, forming a PANoptosome and driving PANoptosis and inflammation. Cell 134 38878777
2021 SARS-CoV-2 inhibits induction of the MHC class I pathway by targeting the STAT1-IRF1-NLRC5 axis. Nature communications 134 34782627
2012 NLRC5 deficiency selectively impairs MHC class I- dependent lymphocyte killing by cytotoxic T cells. Journal of immunology (Baltimore, Md. : 1950) 134 22412192
2013 Rhinovirus-induced calcium flux triggers NLRP3 and NLRC5 activation in bronchial cells. American journal of respiratory cell and molecular biology 125 23815151
2012 NLRC5 regulates MHC class I antigen presentation in host defense against intracellular pathogens. Cell research 124 22491475
2012 Enhanced TLR-induced NF-κB signaling and type I interferon responses in NLRC5 deficient mice. Cell research 116 22473004
2010 NLRC5 deficiency does not influence cytokine induction by virus and bacteria infections. Journal of immunology (Baltimore, Md. : 1950) 98 21148033
2012 Cutting edge: impaired MHC class I expression in mice deficient for Nlrc5/class I transactivator. Journal of immunology (Baltimore, Md. : 1950) 90 22711889
2015 NLRC5 exclusively transactivates MHC class I and related genes through a distinctive SXY module. PLoS genetics 79 25811463
2017 NLRC5/CITA: A Key Player in Cancer Immune Surveillance. Trends in cancer 73 28718425
2011 NLRC5: a newly discovered MHC class I transactivator (CITA). Microbes and infection 73 22209772
2016 NLRC5 regulates cell proliferation, migration and invasion in hepatocellular carcinoma by targeting the Wnt/β-catenin signaling pathway. Cancer letters 72 26975630
2016 NLRC5 elicits antitumor immunity by enhancing processing and presentation of tumor antigens to CD8(+) T lymphocytes. Oncoimmunology 71 27471621
2020 Transcriptional Upregulation of NLRC5 by Radiation Drives STING- and Interferon-Independent MHC-I Expression on Cancer Cells and T Cell Cytotoxicity. Scientific reports 66 32355214
2019 HIV-1 Tat-mediated microglial inflammation involves a novel miRNA-34a-NLRC5-NFκB signaling axis. Brain, behavior, and immunity 62 30872089
2017 Dexmedetomidine (DEX) protects against hepatic ischemia/reperfusion (I/R) injury by suppressing inflammation and oxidative stress in NLRC5 deficient mice. Biochemical and biophysical research communications 59 28784305
2019 Knockdown of LncRNA SCAMP1 suppressed malignant biological behaviours of glioma cells via modulating miR-499a-5p/LMX1A/NLRC5 pathway. Journal of cellular and molecular medicine 52 31207033
2018 NLRC5 deficiency ameliorates diabetic nephropathy through alleviating inflammation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 51 29070585
2015 Reversible ubiquitination shapes NLRC5 function and modulates NF-κB activation switch. The Journal of cell biology 51 26620909
2014 NLRC5 interacts with RIG-I to induce a robust antiviral response against influenza virus infection. European journal of immunology 51 25404059
2012 The nucleotide-binding domain of NLRC5 is critical for nuclear import and transactivation activity. Biochemical and biophysical research communications 50 22310711
2015 NLRC5 regulates TGF-β1-induced proliferation and activation of hepatic stellate cells during hepatic fibrosis. The international journal of biochemistry & cell biology 49 26592197
2013 NLRC5, at the Heart of Antigen Presentation. Frontiers in immunology 49 24319445
2017 Insights into the diversity of NOD-like receptors: Identification and expression analysis of NLRC3, NLRC5 and NLRX1 in rainbow trout. Molecular immunology 48 28432942
2016 NLRC5 shields T lymphocytes from NK-cell-mediated elimination under inflammatory conditions. Nature communications 47 26861112
2019 Long noncoding RNA MEG3 regulates rheumatoid arthritis by targeting NLRC5. Journal of cellular physiology 46 30644097
2015 Respiratory Syncytial Virus Infection Upregulates NLRC5 and Major Histocompatibility Complex Class I Expression through RIG-I Induction in Airway Epithelial Cells. Journal of virology 42 25972545
2013 Expression regulation and function of NLRC5. Protein & cell 42 23483478
2017 NLRC5 deficiency promotes myocardial damage induced by high fat diet in mice through activating TLR4/NF-κB. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 41 28499247
2019 Class I transactivator, NLRC5: a central player in the MHC class I pathway and cancer immune surveillance. Immunogenetics 40 30706093
2019 LncRNA MALAT1 prevents the protective effects of miR-125b-5p against acute myocardial infarction through positive regulation of NLRC5. Experimental and therapeutic medicine 40 32010261
2018 NLRC5 mediates cell proliferation, migration, and invasion by regulating the Wnt/β-catenin signalling pathway in clear cell renal cell carcinoma. Cancer letters 39 30543814
2019 The deficiency of miR-214-3p exacerbates cardiac fibrosis via miR-214-3p/NLRC5 axis. Clinical science (London, England : 1979) 38 31434695
2011 Regulation of immune pathways by the NOD-like receptor NLRC5. Immunobiology 38 22024701
2021 The MHC Class-I Transactivator NLRC5: Implications to Cancer Immunology and Potential Applications to Cancer Immunotherapy. International journal of molecular sciences 36 33671123
2020 MHC class I transactivator NLRC5 in host immunity, cancer and beyond. Immunology 36 32633419
2022 Transcription and splicing regulation by NLRC5 shape the interferon response in human pancreatic β cells. Science advances 35 36103539
2019 NLRC5: A paradigm for NLRs in immunological and inflammatory reaction. Cancer letters 34 30867141
2018 The Long Non-coding RNA MEG3/miR-let-7c-5p Axis Regulates Ethanol-Induced Hepatic Steatosis and Apoptosis by Targeting NLRC5. Frontiers in pharmacology 34 29692724
2014 NLRC5 mediates cytokine secretion in RAW264.7 macrophages and modulated by the JAK2/STAT3 pathway. Inflammation 34 24445959
2021 LC3 and NLRC5 interaction inhibits NLRC5-mediated MHC class I antigen presentation pathway in endometrial cancer. Cancer letters 33 34974132
2012 NLRC5 knockdown in chicken macrophages alters response to LPS and poly (I:C) stimulation. BMC veterinary research 33 22401171
2018 NLRC5 deficiency protects against acute kidney injury in mice by mediating carcinoembryonic antigen-related cell adhesion molecule 1 signaling. Kidney international 32 29907459
2016 Role of NLRC5 in progression and reversal of hepatic fibrosis. Toxicology and applied pharmacology 31 26806094
2016 NLRC5 promotes cell proliferation via regulating the AKT/VEGF-A signaling pathway in hepatocellular carcinoma. Toxicology 31 27338800
2021 MSCs-Derived Extracellular Vesicles Carrying miR-212-5p Alleviate Myocardial Infarction-Induced Cardiac Fibrosis via NLRC5/VEGF/TGF-β1/SMAD Axis. Journal of cardiovascular translational research 30 34508321
2020 The lncRNA XIST promotes the progression of breast cancer by sponging miR-125b-5p to modulate NLRC5. American journal of translational research 29 32774715
2019 Emerging Roles for NLRC5 in Immune Diseases. Frontiers in pharmacology 29 31824312
2018 Knockdown of NLRC5 attenuates renal I/R injury in vitro through the activation of PI3K/Akt signaling pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 29 29655162
2017 NLRC5 promotes cell proliferation via regulating the NF-κB signaling pathway in Rheumatoid arthritis. Molecular immunology 29 28865311
2014 Unusual structural features revealed by the solution NMR structure of the NLRC5 caspase recruitment domain. Biochemistry 29 24815518
2023 NOD-like receptor NLRC5 promotes neuroinflammation and inhibits neuronal survival in Parkinson's disease models. Journal of neuroinflammation 27 37072793
2022 NLRC5 restricts dengue virus infection by promoting the autophagic degradation of viral NS3 through E3 ligase CUL2 (cullin 2). Autophagy 27 36126167
2023 METTL3 facilitates immunosurveillance by inhibiting YTHDF2-mediated NLRC5 mRNA degradation in endometrial cancer. Biomarker research 26 37085864
2021 NLRC5/CITA expression correlates with efficient response to checkpoint blockade immunotherapy. Scientific reports 26 33547395
2021 The Regulatory NOD-Like Receptor NLRC5 Promotes Ganglion Cell Death in Ischemic Retinopathy by Inducing Microglial Pyroptosis. Frontiers in cell and developmental biology 26 34095138
2018 Investigation of single and synergic effects of NLRC5 and PD-L1 variants on the risk of colorectal cancer. PloS one 26 29408916
2016 Silencing NLRC5 inhibits extracellular matrix expression in keloid fibroblasts via inhibition of transforming growth factor-β1/Smad signaling pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 26 27525969
2013 A molecular model of the full-length human NOD-like receptor family CARD domain containing 5 (NLRC5) protein. BMC bioinformatics 26 24044430
2019 NLRC5 negatively regulates LTA-induced inflammation via TLR2/NF-κB and participates in TLR2-mediated allergic airway inflammation. Journal of cellular physiology 25 30945291
2019 The expression of NOD2, NLRP3 and NLRC5 and renal injury in anti-neutrophil cytoplasmic antibody-associated vasculitis. Journal of translational medicine 25 31186034
2024 USF1 transcriptionally activates USP14 to drive atherosclerosis by promoting EndMT through NLRC5/Smad2/3 axis. Molecular medicine (Cambridge, Mass.) 24 38424494
2020 NLRC5 promotes cell migration and invasion by activating the PI3K/AKT signaling pathway in endometrial cancer. The Journal of international medical research 24 32431202
2016 Identification and expressional analysis of NLRC5 inflammasome gene in smolting Atlantic salmon (Salmo salar). Fish & shellfish immunology 24 27640334
2020 NLRC5 negatively regulates inflammatory responses in LPS-induced acute lung injury through NF-κB and p38 MAPK signal pathways. Toxicology and applied pharmacology 23 32710960
2020 NLRC5 promotes transcription of BTN3A1-3 genes and Vγ9Vδ2 T cell-mediated killing. iScience 23 33364588
2020 miR-4319 Suppresses the Growth of Esophageal Squamous Cell Carcinoma Via Targeting NLRC5. Current molecular pharmacology 22 31746301
2020 NLRC5 Inhibits Inflammation of Secretory Phase Ectopic Endometrial Stromal Cells by Up-Regulating Autophagy in Ovarian Endometriosis. Frontiers in pharmacology 22 33013364
2018 Knockdown of NLRC5 inhibits renal fibroblast activation via modulating TGF-β1/Smad signaling pathway. European journal of pharmacology 22 29608899
2012 NLRC5: a NOD-like receptor protein with many faces in immune regulation. Cell research 22 22613950
2023 Macrophage-Specific NLRC5 Protects From Cardiac Remodeling Through Interaction With HSPA8. JACC. Basic to translational science 21 37325412
2020 Innate Immune Molecule NLRC5 Protects Mice From Helicobacter-induced Formation of Gastric Lymphoid Tissue. Gastroenterology 21 32169428
2016 NLRC5, a promising new entry in tumor immunology. Journal for immunotherapy of cancer 21 27437103
2015 NLRC5 Mediates IL-6 and IL-1β Secretion in LX-2 Cells and Modulated by the NF-κB/Smad3 Pathway. Inflammation 21 25820389
2020 NLRC5 deficiency ameliorates cardiac fibrosis in diabetic cardiomyopathy by regulating EndMT through Smad2/3 signaling pathway. Biochemical and biophysical research communications 20 32505342
2017 Deficiency of the NOD-Like Receptor NLRC5 Results in Decreased CD8+ T Cell Function and Impaired Viral Clearance. Journal of virology 20 28615208
2016 Role of zebrafish NLRC5 in antiviral response and transcriptional regulation of MHC related genes. Developmental and comparative immunology 20 27876605
2019 Long noncoding RNA FER1L4 regulates rheumatoid arthritis via targeting NLRC5. Clinical and experimental rheumatology 19 31694750
2022 USP14-mediated NLRC5 upregulation inhibits endothelial cell activation and inflammation in atherosclerosis. Biochimica et biophysica acta. Molecular and cell biology of lipids 18 36372300
2019 The Obligate Intracellular Bacterium Orientia tsutsugamushi Targets NLRC5 To Modulate the Major Histocompatibility Complex Class I Pathway. Infection and immunity 18 30559222
2019 Promotion on NLRC5 upregulating MHC-I expression by IFN-γ in MHC-I-deficient breast cancer cells. Immunologic research 18 31900803
2018 Methylation of the genes ROD1, NLRC5, and HKR1 is associated with aging in Hainan centenarians. BMC medical genomics 18 29394898
2020 NLRC5: new cancer buster? Molecular biology reports 17 31925644
2020 NLRC5 alleviated OGD/R-induced PC12-cell injury by inhibiting activation of the TLR4/MyD88/NF-κB pathway. The Journal of international medical research 17 32790491
2020 Arid2-IR promotes NF-κB-mediated renal inflammation by targeting NLRC5 transcription. Cellular and molecular life sciences : CMLS 17 33090288
2017 NLRC5 silencing ameliorates cardiac fibrosis by inhibiting the TGF‑β1/Smad3 signaling pathway. Molecular medicine reports 17 28713900
2022 Selective autophagy of NLRC5 promotes immune evasion of endometrial cancer. Autophagy 16 35174769
2021 LncRNA MEG3 reverses CCl4-induced liver fibrosis by targeting NLRC5. European journal of pharmacology 16 34536366
2017 NLRC5 polymorphism is associated with susceptibility to chronic periodontitis. Immunobiology 16 28122660
2021 NLRC5 regulates expression of MHC-I and provides a target for anti-tumor immunity in transmissible cancers. Journal of cancer research and clinical oncology 15 33797607
2020 Dexmedetomidine inhibits the invasion, migration, and inflammation of rheumatoid arthritis fibroblast-like synoviocytes by reducing the expression of NLRC5. International immunopharmacology 15 32163856