Affinage

NOD1

Nucleotide-binding oligomerization domain-containing protein 1 · UniProt Q9Y239

Length
953 aa
Mass
107.7 kDa
Annotated
2026-06-10
100 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NOD1 (CARD4) is an intracellular pattern-recognition receptor of the Apaf-1/CED-4 family, comprising an N-terminal CARD, a central nucleotide-binding domain, and C-terminal leucine-rich repeats, that couples cytosolic sensing of bacterial products to inflammatory and cell-fate signaling (PMID:10329646). Ligand engagement drives ATP-dependent oligomerization—purified NOD1 is a monomer that oligomerizes upon addition of the muropeptide ligand γ-Tri-DAP, and binds ATP preferentially over other nucleotides (PMID:22062585); this oligomerization is enhanced during invasive bacterial infection and is required for downstream activation (PMID:11463746). Activated NOD1 recruits the CARD-containing kinase RICK/RIP2 through homophilic CARD-CARD interaction (PMID:10329646, PMID:10224040), and RIP2 kinase activity is required both for its own stability and for downstream cytokine output (PMID:19473975). Signaling proceeds via TAK1 to NF-κB and MAPK (p38, ERK, JNK) activation (PMID:17186025, PMID:20007577), engaging TRAF6/NIK and the IKK complex (PMID:10224040, PMID:11463746) and additional transcriptional effectors such as C/EBPβ (PMID:17666556), to induce proinflammatory cytokines and chemokines and neutrophil recruitment in vivo (PMID:17579072). In parallel, NOD1 promotes programmed cell death, originally as a caspase-9 activator (PMID:10329646) and subsequently as a RIP2- and caspase-8-dependent apoptotic event (PMID:17186025). Beyond infection, NOD1 transduces ER-stress-induced inflammation downstream of the IRE1α/TRAF2 axis (PMID:27007849) and operates cell-autonomously in metabolic and vascular tissues: it localizes to insulin vesicles to recruit Rab1a for insulin trafficking in pancreatic beta cells (PMID:31201384), drives lipolysis and inflammatory signaling in adipocytes via ERK/PKA/HSL and a DAG–PKCδ–IRAK1/4 cascade (PMID:24828250, PMID:30391544), and promotes endothelial VCAM-1 expression and atherosclerosis through the RIP2–NF-κB axis (PMID:30496704). NOD1 activity is constrained by PSMA7-mediated proteasomal degradation (PMID:23839082) and METTL3-directed m6A destabilization of NOD1 and RIPK2 mRNA (PMID:35176453), while HSP90 and SGT1 act as chaperones required for NOD1 stability and activation (PMID:17420470).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1999 High

    Established NOD1 as a CARD-bearing Apaf-1/CED-4 family member that links bacterial-sensing architecture to both NF-κB activation and caspase-9-dependent apoptosis, defining its dual signaling identity.

    Evidence Domain mapping, Co-IP, dominant-negative mutagenesis, caspase and NF-κB reporter assays

    PMID:10224040 PMID:10329646

    Open questions at the time
    • Physiological ligand not yet defined
    • Endogenous oligomerization state untested
  2. 2000 Medium

    Implicated the leucine-rich repeats in conferring responsiveness to bacterial products independent of TLR4/MyD88, positioning NOD1 as a cytosolic sensor.

    Evidence NF-κB reporter assays and co-immunopurification of ligand-binding activity in HEK293T cells with LRR deletion mutants

    PMID:11058605

    Open questions at the time
    • Ligand initially assigned to LPS; later refined to peptidoglycan muropeptides
    • Single lab, no direct structural binding data
  3. 2001 High

    Demonstrated that infection-triggered NOD1 oligomerization assembles a transient NOD1-RICK-IKK complex necessary for NF-κB and JNK activation, defining the signaling assembly.

    Evidence Shigella infection, dominant-negative overexpression, Co-IP, microinjection of LPS, reporter assays

    PMID:11463746

    Open questions at the time
    • Stoichiometry of the complex unresolved
    • Kinetics of complex disassembly not defined
  4. 2002 Medium

    Extended NOD1 partner repertoire to caspase-1, linking it to pro-caspase-1 oligomerization and IL-1β secretion.

    Evidence Reciprocal Co-IP, caspase-1 processing Western blots, IL-1β ELISA in transfected/stable cells

    PMID:12459189

    Open questions at the time
    • Relies on overexpression
    • Endogenous relevance to inflammasome assembly untested
  5. 2006 High

    Genetically separated NOD1 outputs: apoptosis is caspase-8- and RIP2-dependent, whereas JNK/IL-8 responses require TAK1 and RIP2, placing TAK1 as a central downstream node.

    Evidence Caspase-8 and RIP2/TAK1 knockout/dominant-negative, IL-8 ELISA, JNK kinase assays

    PMID:17186025

    Open questions at the time
    • Branch-point selection between apoptosis and inflammation not mechanistically resolved
  6. 2007 High

    Identified HSP90 and SGT1 as chaperones required for NOD1 protein stability and activation respectively, establishing a folding-dependent regulatory layer.

    Evidence siRNA knockdown, pharmacological HSP90 inhibition, cellular NOD1 activation assays with Chp1 negative control

    PMID:17420470

    Open questions at the time
    • Direct chaperone-NOD1 binding interface not mapped
  7. 2007 High

    Showed in vivo that NOD1/RICK drive chemokine (CXCL1, CCL2) production, iNOS expression, and neutrophil recruitment, demonstrating physiological inflammatory function and a novel C/EBPβ transcriptional arm.

    Evidence Nod1-/- and RICK-/- cells and mice, cytokine ELISA, EMSA and reporter assays in epithelial cells

    PMID:17579072 PMID:17666556

    Open questions at the time
    • Mechanism of C/EBPβ activation independent of protein synthesis undefined
  8. 2009 High

    Established that RIP2 kinase activity is required for RIP2 stability and for NOD1/NOD2-driven cytokine production, identifying the kinase as a tractable signaling chokepoint.

    Evidence Retroviral kinase-dead RIP2 mutants, protein-level Western blots, cytokine assays in vitro and in vivo

    PMID:19473975

    Open questions at the time
    • Relevant RIP2 autophosphorylation substrates not enumerated
  9. 2011 High

    Reconstituted NOD1 activation biochemically, showing ligand-induced oligomerization, ATP-binding specificity, and direct binding to pro-apoptotic Bid, plus chemical-probe modulation of conformation and localization.

    Evidence Gel-sieve chromatography, fluorescence polarization, purified protein binding; HTS small-molecule inhibitors with conformational and imaging assays

    PMID:21802003 PMID:22062585

    Open questions at the time
    • No high-resolution structure of activated oligomer
    • Functional role of NOD1-Bid interaction in cells untested
  10. 2013 High

    Defined PSMA7 as a direct NOD1-interacting factor driving proteasomal turnover, establishing negative regulation of NOD1 abundance.

    Evidence Y2H, Co-IP, GST-pulldown, ubiquitin assay, siRNA with NF-κB/apoptosis readouts

    PMID:23839082

    Open questions at the time
    • E3 ligase mediating NOD1 ubiquitination not identified
  11. 2016 High

    Placed NOD1/NOD2 downstream of the IRE1α/TRAF2 ER-stress pathway, connecting unfolded-protein-response signaling to RIP2-dependent inflammation.

    Evidence NOD1/2-deficient mouse and human cells, ER stress inducers, TUDCA/IRE1α inhibitors, Brucella infection, IL-6 measurement

    PMID:27007849

    Open questions at the time
    • Whether ER stress generates an endogenous NOD1 ligand or activates it ligand-independently is unresolved
  12. 2015 High

    Demonstrated tissue-level consequences of NOD1 activation in the heart, with NF-κB-dependent impairment of Ca2+ handling and contractile function.

    Evidence NOD1-/- mice, C12-iE-DAP agonist, echocardiography, patch-clamp, Ca2+ imaging, NF-κB inhibition

    PMID:25824149

    Open questions at the time
    • Cell type within myocardium mediating the effect not isolated
  13. 2018 High

    Established endothelial NOD1 as a driver of leukocyte adhesion and atherosclerosis via the RIP2-NF-κB-VCAM-1 axis, responsive to peptidoglycan and oxidized LDL.

    Evidence NOD1-/-Apoe-/- mice, endothelial stimulation, VCAM-1 and adhesion assays, RIP2-NF-κB pharmacological inhibition

    PMID:30496704

    Open questions at the time
    • Direct sensing of oxLDL versus indirect activation not distinguished
  14. 2019 High

    Revealed cell-autonomous metabolic functions: NOD1/RIP2 localize to insulin vesicles to recruit Rab1a for insulin trafficking, and NOD1 inhibits hepatocellular carcinoma proliferation by binding and suppressing SRC.

    Evidence Nod1-/-/Rip2-/- beta cells with fractionation/colocalization and glucose tolerance tests; Co-IP, cell-cycle analysis and xenografts for SRC suppression

    PMID:31201384 PMID:31872284

    Open questions at the time
    • How vesicle localization is targeted versus plasma-membrane sensing is unclear
    • SRC interaction surface not mapped
  15. 2020 Medium

    Expanded NOD1 to antiviral sensing, where it binds viral RNA and promotes MDA5-MAVS and modulates TRAF3-MAVS complex formation to boost type I IFN.

    Evidence Co-IP, poly(I:C) binding, IFN reporters, zebrafish NOD1-/- survival, human cell confirmation

    PMID:32169843

    Open questions at the time
    • Primarily teleost model
    • Direct RNA-binding region of NOD1 undefined
  16. 2021 High

    Defined NOD1 in myeloid cells as a driver of immunosuppression, sustaining arginase-1 and MDSC expansion through autophagy-dependent macrophage reprogramming in colorectal cancer.

    Evidence Nod1-/- mice, bone-marrow chimeras, autophagy inhibitors, arginase-1 assays, colorectal cancer model

    PMID:33503439

    Open questions at the time
    • Endogenous ligand sustaining systemic NOD1 activation in tumors not defined
  17. 2022 Medium

    Identified METTL3-directed m6A modification as a post-transcriptional brake on NOD1 and RIPK2 expression via YTHDF1/2-mediated mRNA decay.

    Evidence METTL3 and YTHDF1/2 siRNA, mRNA stability assays, NOD1/RIPK2 expression and cytokine readouts in macrophages

    PMID:35176453

    Open questions at the time
    • Specific m6A sites on NOD1 transcript not mapped
    • Single lab
  18. 2024 Medium

    Linked NOD1 stabilization by the bacterial toxin BFT-1 to a kinase-scaffolding role with GAK in phosphorylating NUMB, activating NOTCH1-HEY1 signaling to expand breast cancer stem cells.

    Evidence Direct BFT-1 binding and stability assays, NOD1-GAK Co-IP, NUMB phosphorylation/degradation, NOTCH reporter, ALDH+ sorting

    PMID:38437016

    Open questions at the time
    • Whether NOD1 itself has kinase activity versus scaffolds GAK is unresolved
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single sensor selects among its divergent outputs—inflammation, apoptosis, antiviral IFN, vesicular trafficking, and tumor-context signaling—as a function of ligand, tissue, and partner availability remains unresolved.
  • No structural model of the activated NOD1 oligomer in any output context
  • Endogenous ligands driving non-infectious (metabolic, vascular, tumor) functions undefined
  • Determinants of subcellular targeting versus cytosolic signaling unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0060090 molecular adaptor activity 3 GO:0140096 catalytic activity, acting on a protein 2 GO:0003723 RNA binding 1 GO:0140657 ATP-dependent activity 1
Localization
GO:0005829 cytosol 2 GO:0005886 plasma membrane 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-8953897 Cellular responses to stimuli 1 R-HSA-9612973 Autophagy 1
Partners
CASP1GAKMDA5PSMA7RIPK2SRCTRAF3TRAF6
Complex memberships
NOD1-RICK/RIP2-IKK signaling complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 NOD1 (CARD4) was identified as an Apaf-1/CED-4 family member containing an N-terminal CARD, a nucleotide-binding domain, and C-terminal leucine-rich repeats. It specifically activated caspase-9 and promoted caspase-9-induced apoptosis, requiring both the CARD and P-loop for function. NOD1 also induced NF-κB activation and physically bound RICK (a CARD-containing kinase) via homophilic CARD-CARD interaction; NOD1 mutants inhibited RICK-induced NF-κB but not TNF-α-induced NF-κB. Protein domain mapping, co-immunoprecipitation, dominant-negative mutant overexpression, caspase activity assays, NF-κB reporter assays The Journal of biological chemistry High 10329646
1999 CARD4/NOD1 interacts with the serine-threonine kinase RICK and potently induces NF-κB activity through TRAF-6 and NIK signaling molecules. Coexpression of CARD4 also augmented caspase-9-induced apoptosis. Co-immunoprecipitation, NF-κB reporter gene assays, overexpression in cell lines The Journal of biological chemistry High 10224040
2000 NOD1 confers responsiveness to bacterial lipopolysaccharides in a TLR4- and MyD88-independent manner in HEK293T cells expressing trace amounts of NOD1. The leucine-rich repeats of NOD1 were required for LPS-induced NF-κB activation. A LPS-binding activity was specifically co-immunopurified with NOD1 from cytosolic extracts. NF-κB reporter assays in HEK293T cells, co-immunopurification of LPS-binding activity, LRR deletion mutants The Journal of biological chemistry Medium 11058605
2001 Upon infection with invasive Shigella flexneri, CARD4/NOD1 undergoes enhanced oligomerization, which is necessary for NF-κB induction. Dominant-negative CARD4 blocks both NF-κB and JNK activation by S. flexneri and microinjected LPS. S. flexneri infection triggers formation of a transient complex involving CARD4, RICK, and the IKK complex. Dominant-negative overexpression, NF-κB/JNK reporter assays, co-immunoprecipitation of CARD4-RICK-IKK complex, microinjection of LPS EMBO reports High 11463746
2002 NOD1 binds to both RIP2 and caspase-1 via CARD-CARD interactions. NOD1 enhances pro-caspase-1 oligomerization and processing, and augments caspase-1-induced IL-1β secretion as well as LPS-induced IL-1β secretion in transfected and stably expressing cells. Co-immunoprecipitation, Western blot for caspase-1 processing, IL-1β ELISA, stable transfection Biochemical and biophysical research communications Medium 12459189
2006 Nod1-dependent apoptosis is a caspase-8-mediated event that requires RIP2. In contrast, Nod1-dependent JNK activation and IL-8 production do not require caspase-8 but do require TAK1 and RIP2, placing TAK1 as a key downstream node in the Nod1 signaling pathway. Caspase-8 knockout/dominant-negative experiments, RIP2 and TAK1 knockdown/knockout, IL-8 ELISA, JNK kinase assays Cell death and differentiation High 17186025
2007 SGT1 positively regulates NOD1 activation. siRNA depletion of SGT1 prevented multiple NOD1-dependent cellular responses without affecting NOD1 protein stability or downstream signaling molecules. HSP90 depletion or pharmacological inhibition caused loss of NOD1 protein. Depletion of Chp1 (mammalian Rar1 orthologue) had no effect on NOD1-dependent activation. siRNA knockdown, pharmacological HSP90 inhibition, cell-based NOD1 activation assays Proceedings of the National Academy of Sciences of the United States of America High 17420470
2007 Nod1 stimulation in primary peritoneal mesothelial cells induces potent secretion of CXCL1 and CCL2 chemokines, as well as inducible NO synthase expression; these responses require RICK. In vivo intraperitoneal administration of a synthetic Nod1 agonist elicited chemokine production and neutrophil recruitment in wild-type but not RICK-deficient mice. Nod1/RICK-mediated chemokine responses cooperated with IFN-γ in NO production. Listeria-induced CXCL1 production was significantly reduced in Nod1- or RICK-deficient cells. Primary cell stimulation, cytokine ELISA, RICK-deficient mice (in vivo), Nod1-deficient cells, siNOS expression assays Journal of immunology High 17579072
2009 NOD1 is required for H. pylori (cagPAI+)-induced p38 and ERK phosphorylation, as well as NF-κB and AP-1 activation in gastric epithelial cells. siNOD1-expressing cells showed significant reductions in p38 and ERK phosphorylation. NOD1-dependent JNK phosphorylation was observed in response to invasive Shigella but not H. pylori, indicating pathogen-specific responses. Stable siRNA knockdown of NOD1, kinase phosphorylation assays (p38, ERK, JNK), NF-κB and AP-1 reporter assays, pharmacological MAPK inhibitors Journal of immunology High 20007577
2009 Rip2 kinase activity is required for its own protein stability; kinase-dead Rip2 mutants expressed in primary cells had severely compromised protein levels, and this instability could not be rescued by phospho-mimetic mutation. Loss of Rip2 kinase activity abrogated inflammatory cytokine production in response to Nod1 and Nod2 ligands both in vitro and in vivo. Retroviral expression of kinase-dead Rip2 mutants, Western blot for protein levels, cytokine production assays in primary cells and in vivo The Journal of biological chemistry High 19473975
2011 Purified recombinant NOD1 protein exists predominantly as a monomer; addition of the NOD1 ligand γ-Tri-DAP stimulates NOD1 protein oligomerization in vitro. NOD1 binds preferentially to ATP over ADP, AMP, or dATP (nucleotide binding specificity). Purified NOD1 protein directly binds purified pro-apoptotic protein Bid. Gel-sieve chromatography, fluorescence polarization assay for nucleotide binding, in vitro protein-protein binding with purified components Journal of biotechnology High 22062585
2011 2-Aminobenzimidazole compounds (e.g., Nodinitib-1/ML130) selectively inhibit NOD1-induced NF-κB activity. Mechanistic studies indicate these small molecules cause conformational changes of NOD1 in vitro and alter NOD1 subcellular targeting in cells. High-throughput NF-κB reporter assay, multiple counter-screens, in vitro conformational change assays, subcellular localization imaging Chemistry & biology Medium 21802003
2013 PSMA7 (proteasome subunit alpha type-7) directly interacts with NOD1 and downregulates NOD1 expression in a proteasome-dependent manner. Overexpression of PSMA7 inhibits NOD1-mediated apoptosis and NF-κB activation; knockdown of PSMA7 enhances NOD1 activity. Yeast two-hybrid screening, co-immunoprecipitation, GST-pulldown, ubiquitin assay, siRNA knockdown, Western blot Cellular physiology and biochemistry High 23839082
2016 NOD1 and NOD2 are important mediators of ER-stress-induced inflammation. The ER stress inducers thapsigargin and DTT trigger IL-6 production in a NOD1/2-dependent fashion. Brucella abortus-induced inflammation via its type IV secretion effector VceC is TRAF2-, NOD1/2-, and RIP2-dependent; it can be reduced by ER stress inhibitor TUDCA or an IRE1α kinase inhibitor, placing NOD1/2 downstream of the IRE1α/TRAF2 ER stress signaling pathway. NOD1/2-deficient mouse and human cells, ER stress inducers, pharmacological inhibitors (TUDCA, IRE1α inhibitor), bacterial infection model, IL-6 cytokine measurement Nature High 27007849
2019 Nod1 and its downstream adapter Rip2 are required for insulin trafficking in pancreatic beta cells in a cell-autonomous manner. Upon recognizing cognate ligands, Nod1 and Rip2 localize to insulin vesicles and recruit Rab1a to direct insulin trafficking through the cytoplasm. Intestinal lysozyme liberates Nod1 ligands into circulation, enabling long-range gut-islet communication that modulates host glucose tolerance. Nod1-/- and Rip2-/- beta cells, subcellular fractionation and co-localization imaging, Rab1a recruitment assays, intestinal lysozyme manipulation, glucose tolerance tests in mice Cell research High 31201384
2020 NOD1 promotes antiviral signaling by binding viral RNA (poly(I:C)) and regulating the interaction of MDA5 and MAVS. NOD1 enhances MDA5-MAVS complex formation, increasing type I IFN transcription. NOD1 also targets TRAF3 to modulate TRAF3-MAVS complexes. Human NOD1-MDA5 and NOD1-TRAF3 interactions were confirmed by co-immunoprecipitation. Co-immunoprecipitation, RNA binding assays (poly(I:C)), NOD1 knockdown/overexpression, IFN reporter assays, zebrafish NOD1-/- survival experiments, human cell confirmation Journal of immunology Medium 32169843
2021 Systemic Nod1 activation promotes autophagy-dependent reprogramming of macrophages toward an alternative phenotype and induces expansion of myeloid-derived suppressor cells (MDSCs), maintaining their immunosuppressive potential via arginase-1 activity. Myeloid-intrinsic Nod1 expression sustains intra-tumoral arginase-1 levels to foster an immunosuppressive tumor microenvironment during colorectal cancer development. Nod1-/- mice, peritonitis model, autophagy inhibitors, bone marrow chimeras, arginase-1 activity assays, colorectal cancer tumor model Cell reports High 33503439
2018 Endothelial NOD1 triggers VCAM-1 upregulation through the RIP2-NF-κB axis in an autocrine manner in response to peptidoglycan or oxidized LDLs, enhancing firm adhesion of monocytes and neutrophils to the vasculature in vivo. NOD1 genetic inactivation in Apoe-/- mice reduced atherosclerosis burden and monocyte/neutrophil accumulation in atheromata. NOD1-/- Apoe-/- mice, endothelial cell stimulation, VCAM-1 expression assays, leukocyte adhesion assays in vivo, RIP2-NF-κB pathway pharmacological inhibition FASEB journal High 30496704
2015 Selective NOD1 activation with C12-iE-DAP in mice induces cardiac dysfunction with decreased L-type Ca2+ current, reduced [Ca2+]i transients and Ca2+ load, decreased phospho-phospholamban, SERCA, and NCX expression, and increased RyR2 over-phosphorylation causing diastolic Ca2+ leak. These effects were lost in NOD1-/- mice. Co-treatment with NF-κB inhibitor BAY11-7082 prevented iE-DAP-induced cardiac dysfunction and Ca2+ handling impairment, placing NF-κB downstream of NOD1 in this pathway. NOD1-/- mice, selective NOD1 agonist C12-iE-DAP, echocardiography, patch-clamp electrophysiology, Ca2+ imaging, Western blot, NF-κB pharmacological inhibition Cardiovascular research High 25824149
2007 Nod1 activation in lung epithelial cells strongly activates C/EBPβ transcription factors in addition to modest NF-κB activation. This C/EBPβ activation appears independent of de novo protein synthesis, identifying a novel downstream transcriptional pathway from NOD1 in lung epithelium. Electrophoretic mobility shift assay (EMSA), reporter gene assays, protein synthesis inhibitor experiments in BEAS-2B cells The European respiratory journal Medium 17666556
2014 Bacterial peptidoglycan (PGN) stimulates lipolysis in adipocytes via NOD1 in a cell-autonomous manner. NOD1-activating PGN stimulated MAPK (ERK1/2), PKA, and NF-κB in 3T3-L1 adipocytes. NOD1-mediated lipolysis was completely suppressed by simultaneous inhibition of ERK1/2 and PKA, or by hormone-sensitive lipase (HSL) inhibition. WAT explants from NOD1-/- mice did not respond to NOD1-activating PGN. NOD1-/- mouse adipose tissue explants, 3T3-L1 adipocyte stimulation, kinase inhibitors (ERK1/2, PKA, JNK), HSL inhibitor, NF-κB inhibitor, lipolysis assays PloS one High 24828250
2019 NOD1 inhibited proliferation of hepatocellular carcinoma (HCC) cells by directly interacting with proto-oncogene SRC and suppressing SRC activation, thereby inhibiting the SRC/MAPK axis. NOD1 overexpression induced cell cycle arrest at G1 phase and enhanced chemosensitivity to sorafenib and 5-FU in vitro and in vivo. Co-immunoprecipitation (NOD1-SRC interaction), overexpression, siRNA knockdown, cell cycle analysis, xenograft tumor model, Western blot for SRC/MAPK Journal of molecular medicine Medium 31872284
2022 METTL3 (m6A methyltransferase) negatively regulates NOD1 expression by promoting m6A-dependent mRNA degradation of NOD1 and RIPK2 transcripts via YTHDF1 and YTHDF2 m6A readers. METTL3 knockdown increased NOD1 and RIPK2 mRNA stability and expression, activating the NOD1 pathway and amplifying LPS-induced inflammatory responses in macrophages. METTL3 siRNA knockdown, YTHDF1/YTHDF2 silencing, mRNA stability assays, NOD1/RIPK2 expression by Western blot and qPCR, cytokine assays, NOD1 pathway-specific inhibitors Cellular signalling Medium 35176453
2024 BFT-1 (B. fragilis toxin) directly binds to NOD1 and stabilizes NOD1 protein. NOD1, highly expressed on ALDH+ breast cancer stem cells, cooperates with GAK to phosphorylate NUMB, promoting its lysosomal degradation and thereby activating the NOTCH1-HEY1 signaling pathway to increase breast cancer stem cells. Direct binding assays (BFT-1 to NOD1), protein stability assays, co-immunoprecipitation (NOD1-GAK), NUMB phosphorylation and lysosomal degradation assays, NOTCH1 pathway reporter, ALDH+ cell sorting Protein & cell Medium 38437016
2019 NOD1 activation in adipocytes causes diacylglycerol (DAG) accumulation through lipolysis, which activates PKCδ. PKCδ then stimulates IRAK1/4, leading to NF-κB and JNK activation and proinflammatory cytokine expression. Pharmacological inhibition or siRNA-mediated knockdown of IRAK1/4 attenuated NOD1-mediated NF-κB, JNK activation, and cytokine production. NOD1 agonist stimulation of 3T3-L1 adipocytes, DAG measurement, PKCδ activity assays, IRAK1/4 siRNA and pharmacological inhibition, NF-κB/JNK assays, cytokine measurement Biochimica et biophysica acta. Molecular basis of disease Medium 30391544

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB. The Journal of biological chemistry 1124 11087742
2014 NOD1 and NOD2: signaling, host defense, and inflammatory disease. Immunity 649 25526305
2006 Signalling pathways and molecular interactions of NOD1 and NOD2. Nature reviews. Immunology 645 16493424
1999 Nod1, an Apaf-1-like activator of caspase-9 and nuclear factor-kappaB. The Journal of biological chemistry 622 10329646
2001 CARD4/Nod1 mediates NF-kappaB and JNK activation by invasive Shigella flexneri. EMBO reports 497 11463746
2016 NOD1 and NOD2 signalling links ER stress with inflammation. Nature 433 27007849
2000 Human Nod1 confers responsiveness to bacterial lipopolysaccharides. The Journal of biological chemistry 421 11058605
1999 Human CARD4 protein is a novel CED-4/Apaf-1 cell death family member that activates NF-kappaB. The Journal of biological chemistry 307 10224040
2005 Association between a complex insertion/deletion polymorphism in NOD1 (CARD4) and susceptibility to inflammatory bowel disease. Human molecular genetics 243 15790594
2012 NOD1 and NOD2 Signaling in Infection and Inflammation. Frontiers in immunology 220 23162548
2005 NOD1 variation, immunoglobulin E and asthma. Human molecular genetics 213 15718249
2020 NOD1 and NOD2 in inflammatory and infectious diseases. Immunological reviews 158 32677123
2018 NOD1 and NOD2 in inflammation, immunity and disease. Archives of biochemistry and biophysics 157 30578751
2007 Nod1/RICK and TLR signaling regulate chemokine and antimicrobial innate immune responses in mesothelial cells. Journal of immunology (Baltimore, Md. : 1950) 154 17579072
2005 Nod1-mediated endothelial cell activation by Chlamydophila pneumoniae. Circulation research 153 15653568
2009 Helicobacter pylori induces MAPK phosphorylation and AP-1 activation via a NOD1-dependent mechanism. Journal of immunology (Baltimore, Md. : 1950) 148 20007577
2006 Differential release and distribution of Nod1 and Nod2 immunostimulatory molecules among bacterial species and environments. The Journal of biological chemistry 142 16870615
2012 Roles of NOD1 (NLRC1) and NOD2 (NLRC2) in innate immunity and inflammatory diseases. Bioscience reports 136 22908883
2007 SGT1 is essential for Nod1 activation. Proceedings of the National Academy of Sciences of the United States of America 122 17420470
2010 Nod1 and Nod2 regulation of inflammation in the Salmonella colitis model. Infection and immunity 104 20921147
2022 Fusobacterium nucleatum promotes esophageal squamous cell carcinoma progression via the NOD1/RIPK2/NF-κB pathway. Cancer letters 97 35033591
2006 Regulation of Nod1-mediated signaling pathways. Cell death and differentiation 96 17186025
2006 Influence of polymorphisms in the NOD1/CARD4 and NOD2/CARD15 genes on the clinical outcome of Helicobacter pylori infection. Cellular microbiology 90 16819970
2006 Nod1-dependent control of tumor growth. Proceedings of the National Academy of Sciences of the United States of America 89 16446438
2002 Nod1, a CARD protein, enhances pro-interleukin-1beta processing through the interaction with pro-caspase-1. Biochemical and biophysical research communications 89 12459189
2011 Nod1 ligands induce site-specific vascular inflammation. Arteriosclerosis, thrombosis, and vascular biology 85 21330608
2007 Nod1 and Nod2 in innate immunity and human inflammatory disorders. Biochemical Society transactions 84 18031249
2006 Sarcoidosis and NOD1 variation with impaired recognition of intracellular Propionibacterium acnes. Biochimica et biophysica acta 79 16935475
2017 Circulating NOD1 Activators and Hematopoietic NOD1 Contribute to Metabolic Inflammation and Insulin Resistance. Cell reports 78 28273456
2013 NOD1 and NOD2 regulate proinflammatory and prolabor mediators in human fetal membranes and myometrium via nuclear factor-kappa B. Biology of reproduction 78 23740944
2009 The kinase activity of Rip2 determines its stability and consequently Nod1- and Nod2-mediated immune responses. The Journal of biological chemistry 75 19473975
2006 Up-regulation of NOD1 and NOD2 through TLR4 and TNF-alpha in LPS-treated murine macrophages. The Journal of veterinary medical science 75 16757890
2021 Nod1 promotes colorectal carcinogenesis by regulating the immunosuppressive functions of tumor-infiltrating myeloid cells. Cell reports 74 33503439
2006 Association between exposure to farming, allergies and genetic variation in CARD4/NOD1. Allergy 74 16918516
2010 NOD1 and NOD2 regulation of pulmonary innate immunity to Legionella pneumophila. European journal of immunology 70 21108472
2011 Role of NOD1/CARD4 and NOD2/CARD15 gene polymorphisms in cancer etiology. Human immunology 69 21745515
2007 Nod1 and Nod2 induce CCL5/RANTES through the NF-kappaB pathway. European journal of immunology 69 17705131
2019 Intestinal lysozyme liberates Nod1 ligands from microbes to direct insulin trafficking in pancreatic beta cells. Cell research 62 31201384
2010 Dysregulation of p38 and MKP-1 in response to NOD1/TLR4 stimulation in sarcoid bronchoalveolar cells. American journal of respiratory and critical care medicine 61 20851927
2014 Bacterial peptidoglycan stimulates adipocyte lipolysis via NOD1. PloS one 60 24828250
2020 NOD1 Promotes Antiviral Signaling by Binding Viral RNA and Regulating the Interaction of MDA5 and MAVS. Journal of immunology (Baltimore, Md. : 1950) 58 32169843
2021 The long noncoding RNA NARL regulates immune responses via microRNA-mediated NOD1 downregulation in teleost fish. The Journal of biological chemistry 55 33581111
2024 Microbiota enterotoxigenic Bacteroides fragilis-secreted BFT-1 promotes breast cancer cell stemness and chemoresistance through its functional receptor NOD1. Protein & cell 54 38437016
2011 Discovery and characterization of 2-aminobenzimidazole derivatives as selective NOD1 inhibitors. Chemistry & biology 52 21802003
2003 CARD4/NOD1 is not involved in inflammatory bowel disease. Gut 52 12477763
2022 METTL3 regulates LPS-induced inflammatory response via the NOD1 signaling pathway. Cellular signalling 46 35176453
2020 Activation of the pattern recognition receptor NOD1 augments colon cancer metastasis. Protein & cell 46 31956962
2014 Calcineurin/NFAT signaling and innate host defence: a role for NOD1-mediated phagocytic functions. Cell communication and signaling : CCS 46 24479879
2019 Nod1 Imprints Inflammatory and Carcinogenic Responses toward the Gastric Pathogen Helicobacter pylori. Cancer research 45 30696658
2015 Comparative genomic and evolution of vertebrate NOD1 and NOD2 genes and their immune response in miiuy croaker. Fish & shellfish immunology 45 26108036
2006 NOD2/CARD15, NOD1/CARD4, and ICAM-1 gene polymorphisms in Turkish patients with inflammatory bowel disease. Journal of gastroenterology 42 16741608
2017 Molecular characterization, expression and functional analysis of NOD1, NOD2 and NLRC3 in Nile tilapia (Oreochromis niloticus). Fish & shellfish immunology 41 29242132
2014 NOD1 expression is increased in the adipose tissue of women with gestational diabetes. The Journal of endocrinology 40 24829218
2013 Therapeutic targeting of NOD1 receptors. British journal of pharmacology 40 23848281
2012 NOD1 activation induces cardiac dysfunction and modulates cardiac fibrosis and cardiomyocyte apoptosis. PloS one 40 23028889
2009 Investigation of innate immunity genes CARD4, CARD8 and CARD15 as germline susceptibility factors for colorectal cancer. BMC gastroenterology 38 19843337
2019 Role of NOD1/NOD2 receptors in Fusobacterium nucleatum mediated NETosis. Microbial pathogenesis 37 30940608
2013 Nod1 and Nod2 enhance TLR-mediated invariant NKT cell activation during bacterial infection. Journal of immunology (Baltimore, Md. : 1950) 37 24163408
2020 NOD1 and NOD2 Activation by Diverse Stimuli: a Possible Role for Sensing Pathogen-Induced Endoplasmic Reticulum Stress. Infection and immunity 36 32229616
2009 Regulation of Nod1 and Nod2 in first trimester trophoblast cells. American journal of reproductive immunology (New York, N.Y. : 1989) 36 19260860
2017 NOD1 and NOD2: Molecular targets in prevention and treatment of infectious diseases. International immunopharmacology 35 29207344
2016 Nod1 Limits Colitis-Associated Tumorigenesis by Regulating IFN-γ Production. Journal of immunology (Baltimore, Md. : 1950) 35 27183588
2012 NOD1 cooperates with TLR2 to enhance T cell receptor-mediated activation in CD8 T cells. PloS one 35 22848741
2019 NOD1: An Interface Between Innate Immunity and Insulin Resistance. Endocrinology 34 30807635
2018 Endothelial NOD1 directs myeloid cell recruitment in atherosclerosis through VCAM-1. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 33 30496704
2016 High Glucose and Lipopolysaccharide Activate NOD1- RICK-NF-κB Inflammatory Signaling in Mesangial Cells. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 33 27169686
2022 Extracellular vesicles from colorectal cancer cells promote metastasis via the NOD1 signalling pathway. Journal of extracellular vesicles 32 36068649
2019 NOD1 inhibits proliferation and enhances response to chemotherapy via suppressing SRC-MAPK pathway in hepatocellular carcinoma. Journal of molecular medicine (Berlin, Germany) 32 31872284
2010 Orientia tsutsugamushi induced endothelial cell activation via the NOD1-IL-32 pathway. Microbial pathogenesis 32 20470879
2015 NOD1 and NOD2 Genetic Variants in Association with Risk of Gastric Cancer and Its Precursors in a Chinese Population. PloS one 31 25933107
2021 NOD1 in the interplay between microbiota and gastrointestinal immune adaptations. Pharmacological research 30 34273489
2017 The Bacterial Peptidoglycan-Sensing Molecules NOD1 and NOD2 Promote CD8+ Thymocyte Selection. Journal of immunology (Baltimore, Md. : 1950) 30 28202617
2018 Nod1-mediated lipolysis promotes diacylglycerol accumulation and successive inflammation via PKCδ-IRAK axis in adipocytes. Biochimica et biophysica acta. Molecular basis of disease 29 30391544
2011 Expression, purification, and characterization of recombinant NOD1 (NLRC1): A NLR family member. Journal of biotechnology 29 22062585
2021 Mediators of Metabolism: An Unconventional Role for NOD1 and NOD2. International journal of molecular sciences 28 33503814
2014 NOD1, RIP2 and Caspase12 are potentially novel biomarkers for oral squamous cell carcinoma development and progression. International journal of clinical and experimental pathology 28 24817964
2014 Nucleotide-oligomerizing domain-1 (NOD1) receptor activation induces pro-inflammatory responses and autophagy in human alveolar macrophages. BMC pulmonary medicine 28 25253572
2022 Upregulation of NOD1 and NOD2 contribute to cancer progression through the positive regulation of tumorigenicity and metastasis in human squamous cervical cancer. BMC medicine 26 35130902
2006 Complex insertion/deletion polymorphism in NOD1 (CARD4) is not associated with inflammatory bowel disease susceptibility in East Anglia panel. Inflammatory bowel diseases 26 17012967
2015 NOD1, a new player in cardiac function and calcium handling. Cardiovascular research 25 25824149
2007 Contribution of the NOD1/CARD4 insertion/deletion polymorphism +32656 to inflammatory bowel disease in Northern Europe. Inflammatory bowel diseases 25 17285593
2016 Role of nucleotide-binding oligomerization domain 1 (NOD1) in pericyte-mediated vascular inflammation. Journal of cellular and molecular medicine 24 26915562
2020 NLRC3-like 1 inhibits NOD1-RIPK2 pathway via targeting RIPK2. Developmental and comparative immunology 23 32634524
2018 Expression and in vitro assessment of tumorigenicity for NOD1 and NOD2 receptors in breast cancer cell lines. BMC research notes 23 29615116
2015 Expression and activity of NOD1 and NOD2/RIPK2 signalling in mononuclear cells from patients with rheumatoid arthritis. Scandinavian journal of rheumatology 23 26202066
2015 The role of NOD1/CARD4 and NOD2/CARD15 genetic variations in lung cancer risk. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 23 26238283
2013 PSMA7 directly interacts with NOD1 and regulates its function. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 23 23839082
2007 Investigation of NOD1/CARD4 variation in inflammatory bowel disease using a haplotype-tagging strategy. Human molecular genetics 23 17613538
2019 Nucleotide-binding oligomerization domain 1 (NOD1) modulates liver ischemia reperfusion through the expression adhesion molecules. Journal of hepatology 22 30685324
2019 Columbianadin Suppresses Lipopolysaccharide (LPS)-Induced Inflammation and Apoptosis through the NOD1 Pathway. Molecules (Basel, Switzerland) 22 30717343
2017 NOD1 downregulates intestinal serotonin transporter and interacts with other pattern recognition receptors. Journal of cellular physiology 22 29030987
2011 Structures, synthesis, and human Nod1 stimulation of immunostimulatory bacterial peptidoglycan fragments in the environment. Journal of natural products 22 21341753
2020 HPV-mediated down-regulation of NOD1 inhibits apoptosis in cervical cancer. Infectious agents and cancer 21 32021648
2016 The role of NOD1 and NOD2 in host defense against chlamydial infection. FEMS microbiology letters 21 27421958
2014 NOD1 receptor is up-regulated in diabetic human and murine myocardium. Clinical science (London, England : 1979) 21 24934088
2007 The pattern recognition receptor Nod1 activates CCAAT/enhancer binding protein beta signalling in lung epithelial cells. The European respiratory journal 21 17666556
2020 NOD1/NOD2 and RIP2 Regulate Endoplasmic Reticulum Stress-Induced Inflammation during Chlamydia Infection. mBio 20 32487756
2020 Deletion or Inhibition of NOD1 Favors Plaque Stability and Attenuates Atherothrombosis in Advanced Atherogenesis †. Cells 20 32927803
2017 NOD1 deficiency impairs CD44a/Lck as well as PI3K/Akt pathway. Scientific reports 20 28592872
2015 Cigarette Smoke Modulates NOD1 Signal Pathway and Human β Defensins Expression in Human Oral Mucosa. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 20 25968832

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