Affinage

NFKB1

Nuclear factor NF-kappa-B p105 subunit · UniProt P19838

Round 2 corrected
Length
968 aa
Mass
105.4 kDa
Annotated
2026-04-29
130 papers in source corpus 49 papers cited in narrative 50 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NFKB1 encodes the p105 precursor and its processed product p50, which together constitute a central regulatory hub of NF-κB signaling: full-length p105 functions as a cytoplasmic IκB-like inhibitor that sequesters NF-κB dimers and restrains TPL-2/MEK kinase activity via its death domain and ankyrin repeat domain (PMID:12399470, PMID:12832462), while the p50 subunit forms homodimers that constitutively repress target genes through HDAC-1 recruitment or activate anti-inflammatory genes such as IL-10 through CBP association, and heterodimerizes with RelA to drive canonical NF-κB-dependent transcription (PMID:11931769, PMID:16835236, PMID:9802878). Generation of p50 occurs both cotranslationally—where a glycine-rich region acts as a proteasomal processing stop signal—and post-translationally via IKK-mediated Ser927 phosphorylation of p105 triggering ubiquitin-dependent limited proteolysis by the 26S proteasome (PMID:9529257, PMID:8087845, PMID:11976329). Heterozygous loss-of-function mutations in NFKB1 cause common variable immunodeficiency in humans through haploinsufficiency of p105/p50 and defective B-lymphocyte differentiation (PMID:26279205).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1987 High

    Identification of KBF1 as a 48 kDa MHC class I enhancer-binding factor established the existence of a shared nuclear factor for MHC gene regulation, setting the stage for its molecular cloning.

    Evidence DNA affinity purification from nuclear extracts with gel retardation and DNase I footprinting

    PMID:3322806

    Open questions at the time
    • Protein identity and gene unknown at this stage
    • Relationship to NF-κB not yet established
  2. 1990 High

    Cloning of KBF1/p50 revealed it as the DNA-binding subunit of NF-κB and a member of the Rel family, unifying KBF1, NF-κB, v-rel, and Drosophila dorsal into a single transcription factor superfamily.

    Evidence cDNA cloning, sequence analysis, in vitro DNA-binding and functional assays

    PMID:2203531

    Open questions at the time
    • How p50 is generated from its precursor was unknown
    • Partner subunit diversity not yet defined
  3. 1993 High

    Mapping of a specificity-determining subdomain within the p50 RHD resolved how p50 and RelA discriminate between κB motifs, establishing that four residues in the N-terminal RHD control DNA sequence selectivity.

    Evidence Domain-swap fusion proteins, site-directed mutagenesis, EMSA with selective DNA motifs

    PMID:8321192

    Open questions at the time
    • Structural basis of specificity not yet visualized
    • In vivo relevance of differential site selection unresolved
  4. 1994 High

    Demonstration that the ubiquitin-proteasome pathway generates p50 from p105 by limited proteolysis solved the biogenesis problem, showing that the C-terminal IκB-like region is degraded while the N-terminal p50 domain is spared.

    Evidence In vitro processing assay with proteasome inhibitors, yeast proteasome mutants, ubiquitin conjugation assays

    PMID:8087845

    Open questions at the time
    • Identity of specific E2/E3 enzymes unknown
    • Whether processing is co- or post-translational was unresolved
  5. 1998 High

    Multiple groups dissected p105 processing into cotranslational and post-translational modes, identified the glycine-rich region as a proteasomal stop signal, characterized specific E2 (E2-25K, UBCH5) and E3 (E3κB) enzymes, and showed that IKK-mediated Ser927 phosphorylation triggers signal-induced degradation—together defining a dual-track biogenesis mechanism.

    Evidence In vitro translation with proteasome inhibitors, reconstituted ubiquitination with purified E1/E2/E3, yeast proteasome/ubiquitin mutants, IKK phosphorylation assays, mutagenesis

    PMID:11295495 PMID:9430676 PMID:9529257 PMID:9535861

    Open questions at the time
    • Relative contribution of cotranslational vs. post-translational processing in vivo not quantified
    • Structural basis of GRR-mediated processing arrest unknown
  6. 1992 High

    Discovery that thioredoxin-mediated reduction of Cys62 controls p50 DNA binding introduced redox regulation as a post-translational switch for NF-κB activity.

    Evidence Site-directed mutagenesis of Cys62, EMSA, thioredoxin treatment, co-transfection reporter assay

    PMID:1508666

    Open questions at the time
    • Physiological redox signals regulating Cys62 in vivo not defined
    • Whether redox regulation differs between p50 homodimers and heterodimers unknown
  7. 1998 High

    Genetic ablation of p50 in mice revealed that p50 homodimers are essential for LPS tolerance and TNFα promoter repression, establishing an anti-inflammatory transcriptional function distinct from canonical NF-κB activation.

    Evidence p50−/− macrophages, κB site binding EMSA, TNFα promoter reporter, LPS tolerance assays

    PMID:9802878

    Open questions at the time
    • Corepressor identity mediating p50-dependent repression not yet known
    • Mechanism of p50 homodimer induction during tolerance not defined
  8. 2002 High

    Identification of HDAC-1 as a constitutive p50 homodimer corepressor, displaced by phospho-p65/CBP upon stimulation, provided the mechanistic switch between NF-κB-mediated repression and activation at target promoters.

    Evidence Co-immunoprecipitation, EMSA, ChIP, transfection reporter assays

    PMID:11931769

    Open questions at the time
    • Genome-wide mapping of p50/HDAC-1 vs. p65/CBP promoter occupancy not performed
    • Other corepressors potentially redundant with HDAC-1 not excluded
  9. 2002 High

    Mapping of the p105 death domain as a docking site for IKK1/IKK2 and as the domain required for cytoplasmic sequestration of NF-κB dimers unified the IκB-like and signaling-scaffold functions of p105.

    Evidence Co-IP of endogenous proteins, in vitro kinase assays, DD deletion/point mutants, TNFα stimulation

    PMID:11976329 PMID:12399470

    Open questions at the time
    • Whether other DD-containing proteins compete for IKK binding to p105 is unknown
    • Structural detail of DD–IKK interface not resolved
  10. 2003 High

    Demonstration that p105 inhibits TPL-2 MEK kinase activity through two distinct binding interfaces (death domain and residues 497–534) established p105 as a signal-gating scaffold that couples NF-κB activation to MAP kinase signaling.

    Evidence In vitro kinase assay, co-IP, deletion/point mutagenesis, co-transfection in cells

    PMID:12832462 PMID:16448710

    Open questions at the time
    • Whether p105 degradation is sufficient or necessary for TPL-2 release in all cell types not established
    • Stoichiometry of p105–TPL-2 complex in vivo not determined
  11. 2006 High

    p50 homodimers were shown to activate IL-10 transcription via CBP recruitment at the IL-10 κB element, revealing that p50 homodimers can function as transcriptional activators—not only repressors—depending on coactivator availability.

    Evidence Co-IP of p50–CBP, EMSA, luciferase reporter, p50−/− macrophages, in vivo endotoxemia model

    PMID:16835236

    Open questions at the time
    • Signal that switches p50 from HDAC-1 to CBP association not identified
    • Whether Bcl-3 participates in p50-dependent IL-10 activation not addressed
  12. 2009 High

    Characterization of high-molecular-weight p105/p100 complexes containing multiple NF-κB isoforms, combined with structural resolution of a p50:RelA dimeric-dimer on HIV-1 LTR tandem κB sites, revealed higher-order assembly as a regulatory principle controlling NF-κB kinetics and DNA occupancy.

    Evidence Biochemical fractionation, recombinant reconstitution, X-ray crystallography, EMSA kinetics

    PMID:19524538 PMID:19683540

    Open questions at the time
    • In vivo relevance of dimeric-dimer arrangement beyond HIV-1 LTR not tested
    • How HMW complexes are remodeled during signaling not defined
  13. 2011 High

    Crystal structure of p50 bound to guanine-rich IFN response elements and genome-wide analysis revealed that p50 homodimers repress IFN-stimulated genes through a non-canonical DNA recognition mode, enforcing stimulus specificity at composite promoters.

    Evidence Crystal structure, genome-wide expression, EMSA, p50−/− macrophages with TLR9 stimulation

    PMID:21343618

    Open questions at the time
    • Full repertoire of G-IRE-regulated genes not catalogued
    • Whether p50–G-IRE interaction is modulated by post-translational modifications unknown
  14. 2015 High

    Human genetic studies established that heterozygous loss-of-function NFKB1 mutations cause common variable immunodeficiency through haploinsufficiency, with subsequent characterization of variant-specific mechanisms (degradation, impaired nuclear entry, phosphorylation defects) explaining genotype–phenotype relationships.

    Evidence Whole-exome/genome sequencing, immunoblotting, B-cell phenotyping, luciferase reporter, AP-MS

    PMID:26279205 PMID:28115215

    Open questions at the time
    • Penetrance modifiers not identified
    • Whether immune dysregulation involves p105 scaffold functions (e.g. TPL-2) vs. p50 transcriptional functions not distinguished
  15. 2020 High

    In the tumor microenvironment, PGE2-driven nuclear p50 accumulation redirects STAT1 chromatin binding toward iNOS expression and immunosuppression in MDSCs, revealing a non-canonical p50 function in shaping interferon-γ responses through chromatin-level cooperation with STAT1.

    Evidence p50−/− mice, ChIP-seq for STAT1, PGE2 treatment, pharmacological inhibition, in vivo tumor models

    PMID:32265223

    Open questions at the time
    • Mechanism by which p50 facilitates STAT1 binding is unknown
    • Whether this pathway operates in human tumors not confirmed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of the GRR-mediated proteasomal stop signal, the signal that switches p50 homodimers between HDAC-1 repression and CBP activation, and how p105 scaffold versus p50 transcriptional functions differentially contribute to CVID pathogenesis.
  • No structural model of GRR–proteasome interaction
  • Genome-wide single-cell resolution of p50 dimer switching not achieved
  • Relative disease contribution of p105/TPL-2 vs. p50/transcription not dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 7 GO:0140110 transcription regulator activity 6 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 6 GO:0005829 cytosol 3
Pathway
R-HSA-168256 Immune System 6 R-HSA-162582 Signal Transduction 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-5357801 Programmed Cell Death 2
Partners
CHUKCREBBPHDAC1IKBKBMAP3K8RELARELBTNIP1
Complex memberships
NF-κB p50/p50 homodimerNF-κB p50/p65 heterodimerp105–TPL-2 inhibitory complexp50/HDAC-1 repressive complex

Evidence

Reading pass · 50 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 The DNA-binding subunit of NF-κB (p50) is identical to the transcription factor KBF1, which binds H-2 and β2-microglobulin enhancer sequences; KBF1/p50 displays extensive amino acid sequence homology with the v-rel oncogene product and Drosophila dorsal, placing it in the Rel family. In vitro experiments demonstrated functional homologies between KBF1 and v-rel. cDNA cloning, sequence analysis, in vitro DNA-binding and functional assays Cell High 2203531
1987 KBF1 (later identified as p50) was purified from nuclear extracts by sequence-specific DNA affinity chromatography; a 48 kDa protein was shown after SDS-PAGE, elution, and renaturation to bind both H-2 and β2-microglobulin enhancer sequences, establishing its role as a shared transcriptional regulatory factor for MHC class I genes. Protein purification, gel retardation, DNase I footprinting The EMBO journal High 3322806
1994 The ubiquitin-proteasome pathway is required for processing of the NF-κB1 p105 precursor to p50: p105 processing was blocked by proteasome inhibitors and in yeast proteasome mutants in vitro; the C-terminal IκB-like region of p105 is degraded while the N-terminal p50 domain is released, establishing limited proteolysis by the 26S proteasome as the mechanism of p50 generation. In vitro processing assay with proteasome inhibitors; yeast proteasome mutants; ubiquitin conjugation assays Cell High 8087845
1992 DNA binding activity of p50 (NF-κB subunit) is regulated by redox state via cysteine 62: thioredoxin stimulates p50 DNA binding by reducing a disulfide bond involving Cys62; Cys62→Ser substitution abolishes sensitivity to –SH modifying agents and to thioredoxin stimulation, and co-transfection of thioredoxin with an HIV LTR reporter produces NF-κB-dependent transcriptional activation. Site-directed mutagenesis of p50 Cys62, in vitro DNA-binding EMSA, thioredoxin treatment, disulfide cross-linking detection, co-transfection reporter assay Nucleic acids research High 1508666
1998 p50 is generated by a cotranslational processing event involving the 26S proteasome rather than by post-translational processing of p105; cotranslational folding of sequences near the C-terminus of p50 abrogates proteasome processing and diverts ribosomes toward producing full-length p105, demonstrating that p105 is not the precursor of p50 but rather an independent product. In vitro translation with proteasome inhibitors, pulse-chase labeling, domain-deletion constructs Cell High 9529257
1998 p105 processing to p50 by the ubiquitin-proteasome pathway requires E1, one of two E2s (E2-25K or a UBCH5/UBC4-family member), and a new 50 kDa E3 (named E3κB); the 26S proteasome alone provides all proteolytic activities for processing. A C-terminally truncated p105 form (p97) is processed more efficiently than full-length p105 even when ubiquitinated to similar levels, indicating that the C-terminal region of p105 also restrains proteolytic processing. In vitro ubiquitination reconstitution with purified E1/E2/E3 and 26S proteasomes from HeLa extracts The Journal of biological chemistry High 9535861
1998 p105 processing requires the ubiquitin-proteasome pathway in both yeast and mammalian cells; yeast mutants in 20S proteasome subunits, 19S ATPases, and proteasome-associated isopeptidase doa4 inhibit or abolish processing; a ubiquitinated intermediate accumulates in some mutants. Notably, the glycine-rich region (GRR) required for processing in mammalian cells is not required in yeast, indicating mechanistic differences between species. Yeast genetic screens with proteasome/ubiquitin pathway mutants; immunoblot detection of ubiquitinated intermediates The Journal of biological chemistry High 9430676
1998 A glycine-rich region (GRR) within p105 serves as a processing stop signal for the 26S proteasome, preventing complete degradation and yielding p50. Residues 441–454 (including Lys441/442 as ubiquitination targets and residues 446–454 as a ligase recognition motif) are important for constitutive processing. IKK-mediated phosphorylation of the C-terminal domain (residues 918–934) recruits SCFβ-TrCP ubiquitin ligase, leading to accelerated processing/degradation. Deletion and point mutagenesis of p105, ubiquitination assays, IKK phosphorylation assays, in vitro processing Biochimie High 11295495
1996 NF-κB controls its own inhibitor IκBα through an inducible autoregulatory pathway: the p65 subunit of NF-κB directly activates IκBα gene transcription; newly synthesized IκBα associates with p65, restoring cytoplasmic inhibition. This feedback loop ensures transient nuclear NF-κB activity. Transfection reporter assays, immunoprecipitation, Northern blot; p50/p65 subunit-specific dissection Annual review of immunology High 8717528
2002 The p105 death domain (DD) acts as a docking site for the IKK complex (both IKK1 and IKK2), increasing local IKK concentration near the PEST region and facilitating efficient serine 927 phosphorylation of p105, which is required for signal-induced p105 proteolysis by TNFα. Deletion of the DD or the L841A point mutation (homologous to the lpr mutation in Fas) substantially reduces IKK binding, Ser927 phosphorylation, and p105 proteolysis. Co-immunoprecipitation of endogenous proteins, in vitro kinase assays with purified IKK1/IKK2, stable transfection of DD mutants in HeLa cells, TNFα stimulation The Journal of biological chemistry High 11976329
2003 NF-κB1 p105 serves as a negative regulator of the MEK kinase TPL-2 (Cot) through two distinct interactions: the TPL-2 C-terminus binds p105 residues 497–534, and the TPL-2 kinase domain binds the p105 death domain. Binding to the death domain inhibits TPL-2 MEK kinase activity in vitro, and this inhibition is augmented by the concurrent C-terminal interaction. Both interactions are required for inhibition of TPL-2 activity in co-transfected cells; a C-terminally truncated oncogenic TPL-2 mutant is insensitive to p105 inhibition. In vitro kinase assay, co-immunoprecipitation, deletion/point mutagenesis, co-transfection in cells Molecular and cellular biology High 12832462
2002 p105/IκBγ uses the same binding mode as classical IκBs to interact with NF-κB dimers, requiring at least one p50 subunit (the 'obligatory' subunit) whose NLS is masked by the ankyrin repeat domain. Unlike IκBα, which allows nuclear entry via the exposed NLS of the non-specific subunit, p105 retains the complex in the cytoplasm; the p105 death domain is essential for cytoplasmic sequestration but requires cooperation with the overall three-dimensional scaffold of the ARD–NF-κB dimer assembly. Biochemical binding assays, subcellular fractionation, deletion mutagenesis of p105 death domain and ARD The Journal of biological chemistry High 12399470
2009 p105 and p100 assemble into high-molecular-weight heterogeneous complexes (HMW) that contain multiple NF-κB isoforms. p105 binds NF-κB subunits via two distinct modes: direct RHD–RHD dimerization and ankyrin repeat–mediated binding to preformed NF-κB dimers (IκBγ/IκBδ activities). This HMW complex architecture contributes to regulation of all NF-κB isoforms and controls kinetics of NF-κB dimer availability. Biochemical fractionation of endogenous proteins, purification of recombinant proteins, EMSA, co-immunoprecipitation Molecular cell High 19524538
2009 PKA anchored by AKAP95 phosphorylates p105 (NF-κB1) at a site adjacent to the IKK target region, suppressing TNFα gene expression downstream of TLR4 signaling. This identifies p105 as a substrate of PKA-AKAP95 and establishes crosstalk between the cAMP and TLR4 pathways through PKA-dependent scaffolding at p105. Multigene RNAi screening, cAMP analog experiments, selective PKA anchoring inhibitors, time-lapse microscopy, phosphorylation mapping Science signaling High 19531803
2006 p105 phosphorylation by the oncoprotein kinase Tpl2 does not inhibit Tpl2's intrinsic kinase activity; instead, p105-bound Tpl2 remains catalytically active but uses p105 as a competitive substrate, blocking Tpl2's access to its physiological target MEK1. This establishes p105 as a competitive inhibitor of Tpl2 that sequesters the kinase away from MEK1. In vitro kinase assays with p105 and MEK1 as substrates, co-immunoprecipitation, transfection experiments Biochimica et biophysica acta High 16448710
2001 Signal-induced p105 processing is inhibited by co-expression of p50 or other NF-κB subunits (RelA, c-Rel) that physically interact with p105; newly synthesized p105 is processed more rapidly than accumulated p105 already in complex with p50. LPS-induced p105 degradation in monocytic cells is not coupled to generation of p50, demonstrating that processing and inducible degradation are differentially regulated. Transient transfection in COS7 cells, pulse-chase labeling, immunoprecipitation, LPS stimulation of monocytic cells Oncogene Medium 8649779
2006 Two distinct ubiquitin-dependent mechanisms regulate p105: (1) a Processing Inhibitory Domain (PID) restrains constitutive processing, and its removal allows efficient processing requiring ubiquitination on a single (non-specific) lysine; (2) signal-induced complete degradation requires ubiquitination on multiple lysines. Removal of the PID markedly increases processing efficiency. Deletion mutagenesis, in vitro ubiquitination and processing assays Biochemical and biophysical research communications Medium 16678126
2009 ABIN-1 inhibits NF-κB by blocking p105 processing to p50; ABIN-1 physically interacts with p105 but binding is not required for inhibition of processing — rather, ABIN-1 stabilizes p105 and increases its own levels, potentiating NF-κB inhibition. Inhibition requires the ABIN homology domain (AHD)-2 of ABIN-1 and the Processing Inhibitory Domain (PID) of p105. Co-immunoprecipitation, protein stability assays, domain deletion mutagenesis, p105 processing assays Biochemical and biophysical research communications Medium 19695220
1998 Ceramide (via the cell-permeable C2-ceramide analogue) activates NF-κB primarily by promoting p105 processing to p50, generating predominantly p50/p50 homodimers that lack transactivating activity; ceramide has only a marginal effect on IκBα degradation. TNFα, by contrast, stimulates both IκBα degradation and p105 processing. EMSA, supershift assay, immunoblot scanning densitometry of p105/p50 ratios, luciferase reporter assay The Journal of biological chemistry Medium 9624136
2002 p105 physically interacts with IKK1 and IKK2 in HeLa cells (co-immunoprecipitation of endogenous proteins); this interaction is mediated via the p105 death domain and is required for efficient IKK-mediated Ser927 phosphorylation (confirmed separately in PMID 11976329). Co-immunoprecipitation of endogenous p105 with IKK complex components The Journal of biological chemistry Medium 11976329
1998 p50 homodimers, induced by long-term LPS pre-treatment, bind the positively acting κB3 element of the TNFα promoter and are associated with LPS tolerance: p50-/- macrophages fail to develop LPS tolerance, do not downregulate LPS-induced TNF mRNA with prolonged LPS exposure, and ectopic p50 overexpression reduces TNFα promoter transcriptional activation. Genetic deletion (p50-/- mice), ectopic overexpression, κB site binding analysis (EMSA), TNFα promoter reporter assay The Journal of clinical investigation High 9802878
1998 p105 (lacking the C-terminal half) deficiency in mice leads to enhanced constitutive p50 homodimer formation and elevated inducible NF-κB activity, demonstrating that p105 is indispensable for restraining p50 activity. p50 homodimers function as transcriptional activators or repressors depending on cell type, with NF-κB-regulated genes upregulated in p105-/- thymus but downregulated in p105-/- macrophages. Genetic KO mouse model (p105-/- expressing p50), EMSA, gene expression analysis The Journal of experimental medicine High 9529315
2006 p50/p50 homodimers act as transcriptional activators of IL-10 by binding the κB cis-element at −55/−46 of the IL-10 proximal promoter and forming a complex with the transcriptional co-activator CREB-binding protein (CBP). p50-/- macrophages show decreased IL-10 and increased TNFα/IL-12 in response to LPS, and p50-/- mice are more susceptible to lethal endotoxemia. EMSA, co-immunoprecipitation of p50 with CBP, luciferase reporter assay, p50-/- mouse macrophages The Journal of biological chemistry High 16835236
2002 In resting cells, p50/p50 homodimers bind DNA constitutively in complex with HDAC-1, suppressing NF-κB-dependent gene expression; upon appropriate stimulation, nuclear p65 (phosphorylated) associates with CBP and displaces the repressive p50-HDAC-1 complexes. Phosphorylation of p65 determines whether it associates with CBP (activating) or HDAC-1 (repressive). Co-immunoprecipitation, EMSA, chromatin immunoprecipitation, transfection reporter assays Molecular cell High 11931769
2004 p50 (NF-κB1) is required for unloading-induced skeletal muscle atrophy: Nfkb1-/- mice are resistant to hindlimb-unloading-induced decrease in soleus fiber cross-sectional area, and NF-κB reporter gene activation induced by unloading is completely abolished in Nfkb1-/- soleus. Bcl-3 co-operates with p50 in this pathway. Loss of p50 also abolishes the slow-to-fast myosin isoform shift. Genetic KO (Nfkb1-/-) mice, hindlimb unloading model, fiber cross-sectional area measurement, NF-κB luciferase reporter in vivo, myosin isoform analysis The Journal of clinical investigation High 15546001
2004 p50 (NF-κB1) limits hepatic inflammatory and fibrogenic responses: nfkb1-/- mice develop more severe neutrophilic inflammation and fibrosis after chronic CCl4 injury. The mechanism involves p50-dependent HDAC1-mediated repression of the TNFα promoter in hepatic stellate cells, as nfkb1-/- cells express TNFα promoter activity, mRNA, and protein inappropriately. Nfkb1-/- mouse model, chronic CCl4 liver injury, hepatic stellate cell isolation, TNFα promoter-reporter assay, HDAC1 co-repressor mechanism analysis The American journal of pathology High 15743782
2011 NF-κB p50 homodimers repress a subset of IFN-inducible genes through binding to guanine-rich IFN response elements (G-IREs). Structural and genome-wide analyses identified this novel p50-G-IRE interaction; p50 deficiency leads to inappropriate IFN-β production in response to bacterial DNA (TLR9 signaling) due to de-repression of the IFNβ enhancer G-IRE, enforcing stimulus specificity of composite promoters. Genome-wide expression analysis, EMSA, crystal structure of p50 bound to G-IRE, mathematical modeling, p50-/- macrophages with TLR9 stimulation Science signaling High 21343618
1993 DNA-binding specificity of NFKB1 (p50) versus RelA (p65) is conferred by a subdomain within the Rel Homology Domain (RHD): substitution of four amino acids from NFKB1 into RelA transfers NFKB1-selective DNA-binding specificity to RelA. A single amino acid change (His→Arg) within the NFKB1 N-terminal 34 residues switches specificity toward the RelA-selective motif, identifying a discrete specificity-determining subdomain. Domain-swap fusion proteins, site-directed mutagenesis, EMSA with NFKB1- and RelA-selective DNA motifs Molecular and cellular biology High 8321192
1995 The dimerization domain of RelB was characterized using p50 and p52 as partners; a structural core of ~110 residues is sufficient for stable Rel/NF-κB dimer formation. Conserved residues in the dimerization domain also contribute to kappa B DNA recognition. Dimerization-defective mutants can be rescued by compensatory mutations introduced in trans in the dimerization partner p50, demonstrating intermolecular complementation. Mutagenesis of >50 RelB mutants, dimerization assays, DNA-binding assays with p50 and p52 as partners, trans-rescue experiments Molecular and cellular biology High 7760806
1998 p50 suppresses apoptosis during EMCV infection: p50-/- and p65-/- murine embryonic fibroblasts undergo accelerated, premature apoptotic cytotoxicity following EMCV infection (beginning at 6 h), while wild-type cells are protected. In p50-/- mice, this accelerated apoptosis of infected cells allows host clearance of virus before viral burst, reducing viral burden. p50 is thus required for NF-κB-dependent suppression of apoptosis in vivo. p50-/- and p65-/- mouse MEFs, EMCV infection, apoptosis assays (plasma membrane and nuclear changes), viral burden measurement in vivo Journal of virology High 9621024
2009 Crystal structure of p50:RelA (NF-κB) heterodimer bound to the tandem κB sites of the HIV-1 LTR reveals a dimeric-dimer arrangement: two p50:RelA dimers bind both adjacent sites simultaneously, interacting through protein contacts accommodated by DNA bending. The two dimers clamp DNA from opposite faces and form a topological trap; biochemical analyses show apparent anti-cooperativity but enhanced kinetic stability (slow on/off rates) for this higher-order complex. X-ray crystallography, EMSA kinetic analysis, biochemical binding studies Journal of molecular biology High 19683540
2004 Bee venom (BV) and its major component melittin directly bind to the p50 subunit of NF-κB as measured by surface plasmon resonance (BV: Kd = 4.6×10⁻⁶ M; melittin: Kd = 1.2×10⁻⁸ M), inhibiting p50 translocation and NF-κB DNA-binding/transcriptional activity, thereby blocking LPS-induced inflammatory gene expression. Surface plasmon resonance, gel mobility shift assay, luciferase reporter, Western blotting, in vivo arthritis models Arthritis and rheumatism Medium 15529353
2004 IL-10 inhibits nuclear NF-κB by selectively inducing nuclear translocation and DNA-binding of p50/p50 homodimers in human monocytic cells; IL-10 pre-treatment blocks p65 translocation induced by TNFα while not altering p50 translocation. In p105/p50-deficient macrophages, IL-10 fails to inhibit constitutive MIP-2α and IL-6 production, establishing p50 as the mediator of IL-10's nuclear NF-κB inhibitory effect. EMSA, nuclear/cytoplasmic fractionation, p105/p50-/- macrophages, cytokine measurement Clinical and experimental immunology High 14678266
2006 IKKβ-NF-κB signaling activates a proapoptotic JNK cascade through induction of GADD45α → MKK4 → JNK in response to arsenite; this proapoptotic role is dependent on p50 (not p65/RelA), and p50 increases GADD45α protein stability by suppressing its ubiquitination and proteasome-dependent degradation, revealing a novel transcription-independent function of p50 in regulating protein modification. IKKβ overexpression, siRNA knockdown, GADD45α ubiquitination assay, JNK activation assays, p50-specific dependency demonstrated by subunit-specific knockdown The Journal of cell biology Medium 17116751
2010 HDAC inhibition (by trichostatin A) induces acetylation of NF-κB p50 at lysine residues, increases nuclear p50 and p50 DNA-binding activity, and protects against cardiac ischemia-reperfusion injury; this cardioprotection is abolished by genetic deletion of p50 or siRNA knockdown of p50, establishing that p50 acetylation is required for HDAC inhibitor-mediated cardioprotection. p50-/- mice, TSA treatment, Langendorff heart perfusion, immunoprecipitation with anti-acetylation antibody, EMSA, luciferase reporter, siRNA knockdown in H9c2 cells American journal of physiology. Heart and circulatory physiology Medium 20382965
2013 Resolvin D1 (RvD1) triggers phosphorylation and proteasomal degradation of p105 to generate p50, which then accumulates in the nucleus as p50/p50 homodimers, suppressing TNFα expression and restoring efferocytosis; knockdown of p50 abolishes RvD1's ability to suppress TNFα and restore efferocytosis, establishing p50/p50 homodimers as the effector of RvD1-mediated inflammation resolution. siRNA knockdown of p50, nuclear fractionation, EMSA with supershift, murine peritonitis model, efferocytosis assay Journal of cell science Medium 23788426
2015 Intracellular annexin A2 (ANXA2) binds to the p50 subunit of NF-κB in a calcium-independent manner; the ANXA2-p50 complex translocates to the nucleus and increases NF-κB transcriptional activity, upregulating IL-6 and contributing to anti-apoptotic signaling and gemcitabine resistance in pancreatic cancer cells. Co-immunoprecipitation, nuclear fractionation, luciferase reporter assay, siRNA knockdown, ANXA2 mutant (Y23A) Cell death & disease Medium 25611381
2013 An NF-κB p50/p65 responsive site was mapped to ~178 nt upstream of the MIR155HG transcription start site; the −178 site is specifically bound by the p50/p65 heterodimer (demonstrated by EMSA and ChIP), and mutation of this site abolishes p65-induced reporter gene activation, establishing MIR155HG (miR-155 precursor) as a direct NF-κB target gene requiring p50/p65. EMSA, supershift assay, ChIP, deletion and site-directed mutagenesis of the MIR155HG promoter, luciferase reporter BMC molecular biology Medium 24059932
2015 NFKB1 p50 haploinsufficiency (due to heterozygous loss-of-function mutations causing in-frame exon skipping or frameshift with degradation of altered protein) causes common variable immunodeficiency (CVID) in humans; residual p105 and p50 from the non-mutated allele were normal, and all carriers showed B-lymphocyte differentiation defects, establishing NFKB1 haploinsufficiency as a monogenic cause of CVID. Whole-exome/genome sequencing, immunoblotting, B-cell immunophenotyping, lymphocyte stimulation assays in patient-derived cells American journal of human genetics High 26279205
2017 Distinct heterozygous NFKB1 missense and nonsense variants produce mechanistically different functional defects: p.R157X causes proteasome-dependent degradation of both truncated and wild-type proteins leading to dramatic loss of p50/p105; p.H67R reduces nuclear entry of p50 and decreases transcriptional activity in luciferase assays; p.I553M reduces p105 phosphorylation and stability without affecting p50 function. Affinity purification mass spectrometry shows both missense variants alter p50/p105 protein-protein interactions. Luciferase reporter, nuclear fractionation, immunoblotting, proteasome inhibitor treatment, affinity purification mass spectrometry (AP-MS) The Journal of allergy and clinical immunology High 28115215
2014 Eriocalyxin B (EriB) directly targets cysteine 62 of p50 through its α,β-unsaturated ketone, blocking p50 binding to DNA response elements without affecting p50/p65 dimerization or nuclear translocation; siRNA-mediated knockdown of p50 attenuates EriB-induced apoptosis in hepatocellular carcinoma cells, confirming p50 as the functional target. Activity-based probe profiling, site-directed mutagenesis (Cys62), EMSA, siRNA knockdown, apoptosis assays Oncotarget Medium 25404639
2020 Tumor-derived PGE2 induces nuclear accumulation of p50 NF-κB in monocytic MDSCs, diverting IFNγ responses toward NO-mediated immunosuppression and reducing TNFα expression; at the genome level, p50 promotes STAT1 binding to regulatory regions of iNOS (Nos2) and other IFNγ-dependent genes. Ablation of p50 or pharmacologic inhibition of EP2 or NO reprograms MDSCs to a NOS2^low/TNFα^high phenotype restoring antitumor IFNγ activity. p50-/- mice, PGE2 treatment, nuclear fractionation, ChIP-seq for STAT1, pharmacological inhibition, in vivo tumor models Cancer research High 32265223
2009 Inactivation of NF-κB p50 in mice leads to hepatic insulin sensitization via post-translational inhibition of p70S6K: p50-KO livers show reduced IKK2/IKKγ activity, which prevents IKK2-mediated stabilization of S6K1 protein; elevated TNFα in p50-KO livers promotes S6K1 proteasomal degradation. Reconstitution of S6K1 in the liver of p50-KO mice blocks the increased insulin sensitivity. p50-/- mice, hyperinsulinemic-euglycemic clamp, hepatocyte primary culture, IKK2 activity assay, MG132 proteasome inhibition, adenoviral S6K1 reconstitution The Journal of biological chemistry Medium 19433583
2010 TNFα suppresses angiotensinogen (AGT) expression in renal proximal tubular cells through formation of p50/p50 homodimers: TNFα induces both p50/p65 and p50/p50 dimer formation detected by EMSA/supershift; gene silencing of p50 (but not p65) attenuates TNFα-induced AGT suppression, establishing p50/p50 homodimers as the NF-κB complex responsible for AGT transcriptional repression. EMSA, supershift assay, siRNA gene silencing of p50 vs. p65, RT-PCR, ELISA for AGT protein American journal of physiology. Cell physiology Medium 20592241
2010 IRAK1BP1 binds the p50 precursor p105 and promotes nuclear translocation of p50/p50 homodimers relative to p50/p65 heterodimers, shifting innate immune cytokine profiles toward increased IL-10 and promoting LPS tolerance. IRAK1BP1-deficient mice lacking this molecular switch show altered NF-κB dimer composition and altered cytokine responses. IRAK1BP1-/- mice, co-immunoprecipitation of IRAK1BP1 with p105, nuclear/cytoplasmic EMSA, cytokine measurement, forward genetic screen Proceedings of the National Academy of Sciences of the United States of America Medium 20534545
1989 The B-cell-specific NF-κB binding site in the immunoglobulin κ enhancer can be converted to a site that binds both NF-κB and the ubiquitous KBF1/p50 by a single nucleotide substitution; NF-κB and KBF1 are functionally different despite highly similar DNA recognition specificities, as demonstrated by transient transfection. Synthetic altered recognition sequences, EMSA, transient transfection functional assays Molecular and cellular biology Medium 2677676
2014 Nfkb1 acts as a haploinsufficient tumor suppressor specifically in the context of DNA alkylation damage: Nfkb1-/- cells accumulate more alkylator-induced mutations (Hprt assay) than wild-type, and Nfkb1-/- mice develop more lymphomas than Nfkb1+/+ after alkylator treatment but not after ionizing radiation. Heterozygous mice develop lymphomas at an intermediate rate while retaining functional p50, confirming haploinsufficiency. Hprt mutation assay, in vivo tumor induction with alkylating agents vs. ionizing radiation, Nfkb1-/- and Nfkb1+/- mice Oncogene Medium 25043302
1999 Activation-induced upregulation of Fas (CD95) requires NF-κB p50-p65 heterodimer binding to a composite κB-Sp1 element at positions −295 to −286 of the human Fas promoter; Sp1 binds constitutively in resting cells while p50-p65 binding is inducible upon T-cell activation (PMA/ionomycin). Sp1 and NF-κB binding are mutually exclusive (demonstrated by EMSA displacement with purified recombinant Sp1 and p50). Site-directed mutagenesis of critical guanines abolishes activation-dependent Fas promoter induction. EMSA, supershift, displacement assay with purified recombinant p50 and Sp1, deletion mutants, site-directed mutagenesis, IκBα overexpression, κB-Sp1 concatemer reporter Molecular and cellular biology High 10022897
2020 HSV-1 UL2 protein interacts with NF-κB subunits p65 and p50 (co-immunoprecipitation); amino acids 9–17 of UL2 mediate both NF-κB inhibition and interaction with p65/p50, and UL2 binds the IPT domain of p65. UL2 inhibits NF-κB activity by attenuating TNFα-induced p65 phosphorylation at Ser536 without affecting p65/p50 dimerization or nuclear localization. Co-immunoprecipitation, domain deletion mapping, phosphorylation analysis by Western blot, luciferase reporter assay Frontiers in immunology Medium 32477319
1999 NF-κB p50/RelB complexes regulate transcriptional elongation of c-myb by binding NF-κB sites flanking the transcriptional pause site in c-myb intron I; p50/RelB (but not p50 or RelB alone) prevents the down-regulation of c-myb mRNA and increases transcriptional elongation in MEL cells undergoing HMBA-induced differentiation, blocking erythroid differentiation. Stable transfection of MEL cells with p50 and/or RelB, nuclear run-on transcription assay, c-myb mRNA analysis Oncogene Medium 10602492

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 The NF-kappa B and I kappa B proteins: new discoveries and insights. Annual review of immunology 5257 8717528
2012 Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 3725 23128233
2009 Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. Journal of immunology (Baltimore, Md. : 1950) 2467 19570822
2009 The NF-kappaB family of transcription factors and its regulation. Cold Spring Harbor perspectives in biology 2298 20066092
2011 Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2101 21833088
1994 The ubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappa B. Cell 1921 8087845
1997 A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB. Nature 1833 9252186
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2002 Visualization of interactions among bZIP and Rel family proteins in living cells using bimolecular fluorescence complementation. Molecular cell 1266 11983170
2009 An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell 1202 19878981
2009 A census of human transcription factors: function, expression and evolution. Nature reviews. Genetics 1191 19274049
2009 Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nature genetics 1160 19169254
2011 NF-κB in the liver--linking injury, fibrosis and hepatocellular carcinoma. Nature reviews. Gastroenterology & hepatology 1131 21293511
1999 Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2. Science (New York, N.Y.) 1125 10426996
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
1993 NF-kappa B controls expression of inhibitor I kappa B alpha: evidence for an inducible autoregulatory pathway. Science (New York, N.Y.) 1050 8096091
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
1990 The DNA binding subunit of NF-kappa B is identical to factor KBF1 and homologous to the rel oncogene product. Cell 909 2203531
1994 Physical association and functional antagonism between the p65 subunit of transcription factor NF-kappa B and the glucocorticoid receptor. Proceedings of the National Academy of Sciences of the United States of America 898 8290595
2009 Mutations of multiple genes cause deregulation of NF-kappaB in diffuse large B-cell lymphoma. Nature 869 19412164
2004 A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nature cell biology 841 14743216
2007 Promiscuous mutations activate the noncanonical NF-kappaB pathway in multiple myeloma. Cancer cell 835 17692805
1999 The SCFbeta-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro. Genes & development 832 9990852
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2011 Control of the senescence-associated secretory phenotype by NF-κB promotes senescence and enhances chemosensitivity. Genes & development 819 21979375
2002 The phosphorylation status of nuclear NF-kappa B determines its association with CBP/p300 or HDAC-1. Molecular cell 795 11931769
2004 TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains. Molecular cell 749 15327770
1992 Thioredoxin regulates the DNA binding activity of NF-kappa B by reduction of a disulphide bond involving cysteine 62. Nucleic acids research 722 1508666
1998 Structure of an IkappaBalpha/NF-kappaB complex. Cell 713 9865693
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2006 NF-kappaB1 (p50) homodimers differentially regulate pro- and anti-inflammatory cytokines in macrophages. The Journal of biological chemistry 316 16835236
1998 Cotranslational biogenesis of NF-kappaB p50 by the 26S proteasome. Cell 273 9529257
1995 Nuclear factor-kappa B in rheumatoid synovium. Localization of p50 and p65. Arthritis and rheumatism 249 8849348
2016 NFKB1: a suppressor of inflammation, ageing and cancer. The FEBS journal 245 26663363
2004 Molecular mechanisms of interleukin-10-mediated inhibition of NF-kappaB activity: a role for p50. Clinical and experimental immunology 218 14678266
1998 Regulation of an essential innate immune response by the p50 subunit of NF-kappaB. The Journal of clinical investigation 213 9802878
1987 Purification of KBF1, a common factor binding to both H-2 and beta 2-microglobulin enhancers. The EMBO journal 204 3322806
2015 Haploinsufficiency of the NF-κB1 Subunit p50 in Common Variable Immunodeficiency. American journal of human genetics 202 26279205
2004 Disruption of either the Nfkb1 or the Bcl3 gene inhibits skeletal muscle atrophy. The Journal of clinical investigation 188 15546001
1999 Activation-dependent transcriptional regulation of the human Fas promoter requires NF-kappaB p50-p65 recruitment. Molecular and cellular biology 187 10022897
2004 Antiarthritic effect of bee venom: inhibition of inflammation mediator generation by suppression of NF-kappaB through interaction with the p50 subunit. Arthritis and rheumatism 177 15529353
2018 Loss-of-function nuclear factor κB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans. The Journal of allergy and clinical immunology 173 29477724
2009 Suppression of LPS-induced TNF-alpha production in macrophages by cAMP is mediated by PKA-AKAP95-p105. Science signaling 161 19531803
2006 Heritability and reliability of P300, P50 and duration mismatch negativity. Behavior genetics 155 16826459
1998 Tumor necrosis factor alpha transcription in macrophages is attenuated by an autocrine factor that preferentially induces NF-kappaB p50. Molecular and cellular biology 153 9742085
2006 Proteasome-mediated degradation of IkappaBalpha and processing of p105 in Crohn disease and ulcerative colitis. The Journal of clinical investigation 133 17124531
2009 The Nfkb1 and Nfkb2 proteins p105 and p100 function as the core of high-molecular-weight heterogeneous complexes. Molecular cell 130 19524538
2006 Absence of NF-kappaB subunit p50 improves heart failure after myocardial infarction. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 118 16837548
1998 Chronic inflammation and susceptibility to bacterial infections in mice lacking the polypeptide (p)105 precursor (NF-kappaB1) but expressing p50. The Journal of experimental medicine 117 9529315
2020 Tumor-Derived Prostaglandin E2 Promotes p50 NF-κB-Dependent Differentiation of Monocytic MDSCs. Cancer research 114 32265223
2008 Impaired adult neurogenesis associated with short-term memory defects in NF-kappaB p50-deficient mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 113 18400889
2005 Resolution of inflammation: prostaglandin E2 dissociates nuclear trafficking of individual NF-kappaB subunits (p65, p50) in stimulated rheumatoid synovial fibroblasts. Journal of immunology (Baltimore, Md. : 1950) 111 16272352
2005 Nuclear factor-kappaB1 (p50) limits the inflammatory and fibrogenic responses to chronic injury. The American journal of pathology 108 15743782
2003 NF-kappaB1 p105 negatively regulates TPL-2 MEK kinase activity. Molecular and cellular biology 107 12832462
2017 Damaging heterozygous mutations in NFKB1 lead to diverse immunologic phenotypes. The Journal of allergy and clinical immunology 105 28115215
2018 NFKB1 and Cancer: Friend or Foe? Cells 100 30205516
2009 The biological functions of NF-kappaB1 (p50) and its potential as an anti-cancer target. Current cancer drug targets 100 19519322
1998 The major core protein of messenger ribonucleoprotein particles (p50) promotes initiation of protein biosynthesis in vitro. The Journal of biological chemistry 95 9452484
2012 Expression of NF-κB p50 in tumor stroma limits the control of tumors by radiation therapy. PloS one 91 22761754
1992 Reconstitution of the multiprotein complex of pp60src, hsp90, and p50 in a cell-free system. The Journal of biological chemistry 89 1310678
2006 IKKbeta programs to turn on the GADD45alpha-MKK4-JNK apoptotic cascade specifically via p50 NF-kappaB in arsenite response. The Journal of cell biology 87 17116751
2011 The specificity of innate immune responses is enforced by repression of interferon response elements by NF-κB p50. Science signaling 83 21343618
2014 Loss of Nfkb1 leads to early onset aging. Aging 81 25553648
2008 NF-kappaB transcription factor p50 critically regulates tissue factor in deep vein thrombosis. The Journal of biological chemistry 81 19095643
1998 NF-kappa B p105 processing via the ubiquitin-proteasome pathway. The Journal of biological chemistry 77 9430676
2007 Association of NFKB1, which encodes a subunit of the transcription factor NF-kappaB, with alcohol dependence. Human molecular genetics 76 18079108
2015 Intracellular annexin A2 regulates NF-κB signaling by binding to the p50 subunit: implications for gemcitabine resistance in pancreatic cancer. Cell death & disease 75 25611381
2003 Bcl-3 and NFkappaB p50-p50 homodimers act as transcriptional repressors in tolerant CD4+ T cells. The Journal of biological chemistry 73 14668329
2000 Identification of mouse YB1/p50 as a component of the FMRP-associated mRNP particle. Biochemical and biophysical research communications 69 11162447
2010 miR-335 directly targets Rb1 (pRb/p105) in a proximal connection to p53-dependent stress response. Cancer research 68 20713524
1998 NF-kappaB-mediated inhibition of apoptosis is required for encephalomyocarditis virus virulence: a mechanism of resistance in p50 knockout mice. Journal of virology 67 9621024
2013 Resolvin D1 stimulates efferocytosis through p50/p50-mediated suppression of tumor necrosis factor-α expression. Journal of cell science 65 23788426
2000 Neuroprotective role for the p50 subunit of NF-kappaB in an experimental model of Huntington's disease. Journal of molecular neuroscience : MN 62 11211235
2020 Anti-inflammatory treatment rescues memory deficits during aging in nfkb1-/- mice. Aging cell 61 32915495
2009 Structural basis of HIV-1 activation by NF-kappaB--a higher-order complex of p50:RelA bound to the HIV-1 LTR. Journal of molecular biology 60 19683540
1998 Enzymes catalyzing ubiquitination and proteolytic processing of the p105 precursor of nuclear factor kappaB1. The Journal of biological chemistry 60 9535861
2001 Relative importance of NF-kappaB p50 in mycobacterial infection. Infection and immunity 56 11598086
2015 RelB/p50 complexes regulate cytokine-induced YKL-40 expression. Journal of immunology (Baltimore, Md. : 1950) 55 25681350
2009 Resolution of renal inflammation: a new role for NF-kappaB1 (p50) in inflammatory kidney diseases. American journal of physiology. Renal physiology 53 19458123
2003 Glutamine decreases lipopolysaccharide-induced IL-8 production in Caco-2 cells through a non-NF-kappaB p50 mechanism. Cytokine 53 12849706
2002 Role of p50/CDC37 in hepadnavirus assembly and replication. The Journal of biological chemistry 53 11986322
2001 Mechanisms of ubiquitin-mediated, limited processing of the NF-kappaB1 precursor protein p105. Biochimie 52 11295495
2001 Normal liver regeneration in p50/nuclear factor kappaB1 knockout mice. Hepatology (Baltimore, Md.) 50 11283856
1998 Intestinal NF-kappaB is activated, mainly as p50 homodimers, by platelet-activating factor. Biochimica et biophysica acta 50 9630621
2013 Identification of an NF-κB p50/p65-responsive site in the human MIR155HG promoter. BMC molecular biology 49 24059932
2019 CapG promotes resistance to paclitaxel in breast cancer through transactivation of PIK3R1/P50. Theranostics 48 31660072
2018 Inhibition of Gsk3b Reduces Nfkb1 Signaling and Rescues Synaptic Activity to Improve the Rett Syndrome Phenotype in Mecp2-Knockout Mice. Cell reports 48 29742424
2009 Functional polymorphism of NFKB1 promoter may correlate to the susceptibility of gastric cancer in aged patients. Surgery 47 19231580
2018 Protumor Steering of Cancer Inflammation by p50 NF-κB Enhances Colorectal Cancer Progression. Cancer immunology research 46 29588321
1998 Ceramide activates NFkappaB by inducing the processing of p105. The Journal of biological chemistry 46 9624136
2010 Targeted deletion of NF-kappaB p50 diminishes the cardioprotection of histone deacetylase inhibition. American journal of physiology. Heart and circulatory physiology 44 20382965
2012 Chronic intermittent hypoxia exposure induces atherosclerosis in ApoE knockout mice: role of NF-κB p50. The American journal of pathology 42 22940439
2008 Role of hypercytokinemia in NF-kappaB p50-deficient mice after H5N1 influenza A virus infection. Journal of virology 41 18768968
1995 Lipoarabinomannans derived from different strains of Mycobacterium tuberculosis differentially stimulate the activation of NF-kappa B and KBF1 in murine macrophages. Infection and immunity 41 7729908
2009 Inactivation of NF-kappaB p50 leads to insulin sensitization in liver through post-translational inhibition of p70S6K. The Journal of biological chemistry 38 19433583
1994 The native v-Raf.hsp90.p50 heterocomplex contains a novel immunophilin of the FK506 binding class. The Journal of biological chemistry 37 7520912
2002 The death domain of NF-kappa B1 p105 is essential for signal-induced p105 proteolysis. The Journal of biological chemistry 36 11976329
1995 Characterization of elements determining the dimerization properties of RelB and p50. Molecular and cellular biology 36 7760806
1999 Transcriptional elongation of c-myb is regulated by NF-kappaB (p50/RelB). Oncogene 35 10602492
2010 IRAK1BP1 inhibits inflammation by promoting nuclear translocation of NF-kappaB p50. Proceedings of the National Academy of Sciences of the United States of America 34 20534545
2009 Functional polymorphism of the NFKB1 gene promoter is related to the risk of dilated cardiomyopathy. BMC medical genetics 33 19480714
2019 Late-Onset Antibody Deficiency Due to Monoallelic Alterations in NFKB1. Frontiers in immunology 32 31803180
2010 Tumor necrosis factor-{alpha} suppresses angiotensinogen expression through formation of a p50/p50 homodimer in human renal proximal tubular cells. American journal of physiology. Cell physiology 32 20592241
2006 Inhibition of Helicobacter hepaticus-induced colitis by IL-10 requires the p50/p105 subunit of NF-kappa B. Journal of immunology (Baltimore, Md. : 1950) 32 17082652
2016 NFKB1 regulates human NK cell maturation and effector functions. Clinical immunology (Orlando, Fla.) 31 27923702
2008 Association study of NFKB1 and SUMO4 polymorphisms in Chinese patients with psoriasis vulgaris. Archives of dermatological research 31 18330586
2009 Polymorphic variation in NFKB1 and other aspirin-related genes and risk of Hodgkin lymphoma. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 29 19223558
2009 ABIN-1 negatively regulates NF-kappaB by inhibiting processing of the p105 precursor. Biochemical and biophysical research communications 29 19695220
1996 Inhibition of p105 processing by NF-kappaB proteins in transiently transfected cells. Oncogene 27 8649779
1989 Alteration of a single nucleotide allows efficient binding of H2TF1/KBF1 to the immunoglobulin kappa enhancer B motif. Molecular and cellular biology 27 2677676
2017 Should modulation of p50 be a therapeutic target in the critically ill? Expert review of hematology 26 28402148
2008 The p50 subunit of NF-kappaB is critical for in vivo clearance of the noninvasive enteric pathogen Citrobacter rodentium. Infection and immunity 26 18694964
2006 Phosphorylation of NF-kappaB1/p105 by oncoprotein kinase Tpl2: implications for a novel mechanism of Tpl2 regulation. Biochimica et biophysica acta 26 16448710
1993 Acquisition of NFKB1-selective DNA binding by substitution of four amino acid residues from NFKB1 into RelA. Molecular and cellular biology 26 8321192
2014 Identification and validation of p50 as the cellular target of eriocalyxin B. Oncotarget 25 25404639
2015 Shh and p50/Bcl3 signaling crosstalk drives pathogenesis of BCCs in Gorlin syndrome. Oncotarget 24 26413810
2014 Nfkb1 is a haploinsufficient DNA damage-specific tumor suppressor. Oncogene 24 25043302
2013 Interleukin-10 gene promoter and NFKB1 promoter insertion/deletion polymorphisms in systemic sclerosis. Scandinavian journal of immunology 24 23237063
2006 Two distinct ubiquitin-dependent mechanisms are involved in NF-kappaB p105 proteolysis. Biochemical and biophysical research communications 24 16678126
2004 Interaction of Cep135 with a p50 dynactin subunit in mammalian centrosomes. Cell motility and the cytoskeleton 24 14983524
2002 p105.Ikappa Bgamma and prototypical Ikappa Bs use a similar mechanism to bind but a different mechanism to regulate the subcellular localization of NF-kappa B. The Journal of biological chemistry 24 12399470
2020 Herpes Simplex Virus 1 UL2 Inhibits the TNF-α-Mediated NF-κB Activity by Interacting With p65/p50. Frontiers in immunology 23 32477319
2020 Entropy-driven electrochemiluminescence ultra-sensitive detection strategy of NF-κB p50 as the regulator of cytokine storm. Biosensors & bioelectronics 23 33401144
2019 Upregulated MiR-9-5p Protects Against Inflammatory Response in Rats with Deep Vein Thrombosis via Inhibition of NF-κB p50. Inflammation 23 31463646
2017 Association of NFKB1 and NFKBIA gene polymorphisms with susceptibility of gastric cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 23 28670959
2016 HLA-Cw6 allele, NFkB1 and NFkBIA polymorphisms play no role in predicting response to etanercept in psoriatic patients. Pharmacogenetics and genomics 23 27348478
2021 LncRNA MAFG-AS1 promotes the malignant phenotype of ovarian cancer by upregulating NFKB1-dependent IGF1. Cancer gene therapy 22 34035482
2012 The switch from pRb/p105 to Rb2/p130 in DNA damage and cellular senescence. Journal of cellular physiology 22 21465484
2010 A functional promoter polymorphism in NFKB1 increases susceptibility to endometriosis. DNA and cell biology 22 20218898