Affinage

CHUK

Inhibitor of nuclear factor kappa-B kinase subunit alpha · UniProt O15111

Length
745 aa
Mass
84.6 kDa
Annotated
2026-06-09
91 papers in source corpus 43 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CHUK/IKK-alpha is a serine-threonine kinase, identified by its N-terminal kinase domain plus central leucine-zipper and C-terminal helix-loop-helix domains (PMID:8777433), that operates as a core catalytic subunit of the multiprotein IkappaB kinase (IKK) signalsome which phosphorylates IkappaB proteins to drive NF-kappaB activation (PMID:9346484). IKK-alpha is activated through phosphorylation of its activation-loop residue Ser-176 by NIK and by stress kinases such as HPK1/MEKK1, with an S176E substitution rendering it constitutively active (PMID:9520446, PMID:10523828); in vitro the IKK-alpha homodimer is a comparatively weak kinase while the IKK-alpha/IKK-beta heterodimer is most efficient toward IkappaB-alpha (PMID:10823818, PMID:10593898), and the two kinases are together essential for NF-kappaB activation in vivo (PMID:10898787). A defining feature of IKK-alpha is its selective control of the non-canonical pathway, mediating NIK-dependent p100-to-p52 processing (PMID:14691250) through a hexamer-forming surface, divergent from IKK-beta, that structural analysis shows is required for p100 processing (PMID:27851956), with RelB competing for p100 to set signaling output (PMID:27678221); reciprocally, IKK-alpha restrains canonical IKK-beta-driven IkappaB-alpha degradation as an innate-immunity checkpoint (PMID:16116086). Beyond cytoplasmic kinase activity, nuclear IKK-alpha acts as a chromatin-modifying kinase, phosphorylating histone H3 and modulating RelA acetylation to sustain pro-inflammatory transcription (PMID:18239189, PMID:21402739), and is exploited by HCV—via DDX3X and the viral 3' UTR—to drive an SREBP/CBP-p300 lipogenic program independently of NF-kappaB (PMID:23708292). IKK-alpha additionally performs kinase-independent developmental and structural roles, including epidermal barrier formation via retinoic-acid-regulated transcription (PMID:17351639), placement downstream of p63 and upstream of Notch in keratinocyte differentiation (PMID:17093266, PMID:21435444), and chondrocyte hypertrophy and ECM remodeling rescued by kinase-dead protein (PMID:24023802, PMID:31222033). Distinct cell-type-specific in vivo functions—lymphatic endothelial cells for lymph node formation, hematopoietic cells for B cell homeostasis—have been established by conditional genetics (PMID:34810256), and IKK-alpha behaves as a lung epithelial tumor suppressor whose loss promotes adenoma growth and HIF-1alpha accumulation (PMID:31792060). In humans, biallelic loss of CHUK causes a lethal autosomal recessive fetal syndrome with severe craniofacial and limb malformations (PMID:20961246).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1995 Medium

    Established the protein's existence and domain architecture, predicting that a kinase carrying leucine-zipper and HLH motifs might target transcription factors.

    Evidence cDNA cloning and sequence analysis of murine CHUK

    PMID:8777433

    Open questions at the time
    • No functional kinase substrate identified
    • No demonstration of complex membership or signaling role
  2. 1997 High

    Placed IKK-alpha within the cytokine-responsive IKK signalsome and showed it phosphorylates IkappaB substrates, answering what the kinase does in NF-kappaB signaling.

    Evidence Biochemical purification of the IKK complex from HeLa cells, in vitro kinase assays, dominant-negative analysis

    PMID:9346484

    Open questions at the time
    • Relative contributions of IKK-alpha vs IKK-beta not resolved
    • Upstream activators of the complex not defined
  3. 1998 High

    Defined the upstream activation mechanism by showing NIK phosphorylates IKK-alpha at Ser-176 in the activation loop, with phospho-mimetic and dead alleles toggling activity.

    Evidence In vitro kinase assay and S176A/S176E site-directed mutagenesis

    PMID:9520446

    Open questions at the time
    • Did not establish in vivo pathway selectivity of NIK-IKK-alpha
    • Role of second activation-loop site (S180) not addressed
  4. 1999 High

    Quantified the catalytic hierarchy of IKK isoforms, showing IKK-alpha homodimer is weakly active while the heterodimer is most efficient and that additional stress kinases activate IKK-alpha.

    Evidence Recombinant homodimer/heterodimer kinetics and overexpression of HPK1/MEKK1

    PMID:10523828 PMID:10593898 PMID:10823818

    Open questions at the time
    • In vivo relevance of the heterodimer kinetic advantage untested
    • Differential basal activity mechanism unexplained
  5. 2000 High

    Demonstrated genetically that IKK-alpha and IKK-beta are together indispensable for NF-kappaB activation in vivo, resolving whether the kinases are essential.

    Evidence IKK1/IKK2 double-knockout mice and MEFs with kappaB-lacZ reporter

    PMID:10898787

    Open questions at the time
    • Did not separate unique IKK-alpha functions from IKK-beta
    • Non-canonical pathway not specifically dissected
  6. 2002 Medium

    Refined the catalytic mechanism by showing IKK-alpha homodimers contain non-equivalent active sites and that activation-loop phosphorylation alters active-site conformation via intramolecular autophosphorylation.

    Evidence Recombinant homodimer enzyme kinetics, inhibitor analysis, S176E/S180E mutants

    PMID:12054687

    Open questions at the time
    • Single-lab in vitro analysis
    • Physiological consequence of active-site asymmetry untested
  7. 2003 High

    Identified IKK-alpha-specific signaling roles, both as a Vav-1-associated kinase in T-cell costimulation and as the selective mediator of LMP1-induced non-canonical p100 processing, distinguishing it from IKK-beta.

    Evidence Co-IP/kinase assays in T cells and IKK-alpha-knockout MEFs with NF-kappaB pathway readouts

    PMID:12626540 PMID:14691250

    Open questions at the time
    • Mechanism of IKK-alpha selectivity for p100 not structurally defined
    • Direct p100 phosphorylation by IKK-alpha not shown here
  8. 2004 Medium

    Revealed kinase-independent and NF-kappaB-independent developmental roles and broadened the substrate landscape to RelA Ser-536, separating IKK-alpha functions from canonical signaling.

    Evidence Ikka mutant vs cIkBaDN mouse epistasis in tooth/ectoderm; multi-kinase RelA S536 phosphorylation analysis

    PMID:14960276 PMID:15489227

    Open questions at the time
    • Direct molecular targets of NF-kappaB-independent developmental role unknown
    • RelA S536 phosphorylation has redundant kinase inputs
  9. 2005 High

    Established IKK-alpha as a negative checkpoint on canonical IKK-beta activity and assigned distinct cell-type-specific roles in osteoclast and bone biology.

    Evidence IKK1-knockout macrophages and hematopoietic/conditional knockouts with functional readouts

    PMID:15897281 PMID:16116086

    Open questions at the time
    • Molecular basis of IKK-alpha checkpoint on IKK-beta unclear
    • In vitro vs in vivo discordance in osteoclastogenesis unexplained
  10. 2006 Medium

    Documented nuclear chromatin-associated functions of IKK-alpha at gene promoters, controlling E2F1 transcription and acetylation, and identified p63 as upstream in epidermal development.

    Evidence siRNA, ChIP and co-IP for E2F1; transcriptional assays and mouse genetic complementation for p63

    PMID:16407216 PMID:17093266

    Open questions at the time
    • Direct kinase substrate at chromatin not always identified
    • Generality of promoter recruitment unknown
  11. 2007 Medium

    Defined IKK-alpha as a stress- and damage-responsive nuclear chromatin-modifying kinase (ATM-driven nuclear accumulation; H3 Ser-10 phosphorylation) and showed activation-loop sites differentially gate IRF3/7 vs NF-kappaB outputs.

    Evidence In vitro kinase assays, ChIP, dominant-negative and S176E/S180E mutant reporter assays, knockout MEFs

    PMID:17700524 PMID:18068231 PMID:18239189

    Open questions at the time
    • Single-lab studies for each effector branch
    • How site-specific phosphorylation routes effector choice mechanistically unclear
  12. 2007 High

    Demonstrated epidermal-barrier and innate-defense roles, including RA-regulated transcription in keratinocytes and NF-kappaB-independent ERK-dependent mucin induction.

    Evidence Keratinocyte-specific IKK1 knockout with ChIP; dominant-negative/siRNA mucin assays in vivo

    PMID:17237423 PMID:17351639

    Open questions at the time
    • Direct IKK-alpha substrates in RA-regulated transcription not defined
    • Kinase dependence of mucin role not fully resolved
  13. 2008 High

    Extended IKK-alpha function to BAFF-R survival signaling, hepatic/bile-duct integrity, and axonal development, revealing redundant and IKK1-specific physiological roles.

    Evidence Conditional B-cell and liver knockouts; pharmacological IKK inhibition in neurons

    PMID:18321726 PMID:18606991 PMID:18713867

    Open questions at the time
    • Neuronal study cannot separate IKK-alpha from IKK-beta
    • Mechanism linking IKK1 to Akt/Erk activation unknown
  14. 2010 High

    Identified IKK-alpha as a target of bacterial immune evasion and as a SMAD3-associated driver of NF-kappaB-independent EMT, and established its essential developmental role in humans.

    Evidence InlC direct binding/infection models; co-IP/ChIP for SMAD3-EMT; human loss-of-function genetics; zebrafish domain-specific rescue

    PMID:20692251 PMID:20855622 PMID:20961246 PMID:21081648

    Open questions at the time
    • Direct phosphorylation events in EMT not defined
    • Human syndrome lacks in vitro mechanistic reconstitution
    • Kinase vs HLH requirement differs across species
  15. 2011 High

    Solidified IKK-alpha as a nuclear lineage-specifying chromatin kinase by showing direct occupancy and H3 phosphorylation at the Il17a locus during Th17 differentiation, and placed IKK1 upstream of Notch in keratinocytes.

    Evidence ChIP and non-activatable IKK-alpha knock-in T cells; NICD rescue of IKK1-null keratinocytes

    PMID:21402739 PMID:21435444

    Open questions at the time
    • How nuclear IKK-alpha is targeted to specific loci unknown
    • Direct chromatin substrate repertoire incomplete
  16. 2013 High

    Defined a kinase-independent structural/regulatory role in chondrocyte hypertrophy and ECM remodeling, and a nuclear lipogenic transcriptional program co-opted by HCV.

    Evidence Conditional knockout chondrocytes with kinase-dead rescue; siRNA/inhibitor HCV lipogenesis with SREBP/CBP-p300 readouts

    PMID:23708292 PMID:24023802

    Open questions at the time
    • Molecular partners mediating kinase-independent chondrocyte role not identified
    • Direct IKK-alpha nuclear substrate in HCV program undefined
  17. 2014 Medium

    Linked nuclear IKK-alpha stability to a survivin-2B-dependent p73/UVRAG axis controlling the autophagy-apoptosis switch.

    Evidence Nuclear co-IP, fractionation, knockdown, in vivo tumor model

    PMID:24556686

    Open questions at the time
    • Single-lab pathway
    • Whether IKK-alpha kinase activity is required not established
  18. 2015 Medium

    Mapped the spatial trafficking of IKK-alpha during HCV infection through stress granules to the nucleus, supporting the lipogenesis model.

    Evidence Live and fixed imaging, fractionation, co-IP, siRNA of DDX3X/SG components

    PMID:25740981

    Open questions at the time
    • Trigger for nuclear translocation not defined
    • Single-lab observation
  19. 2016 High

    Provided the structural basis for IKK-alpha's selective non-canonical function, showing a hexamer-forming surface required for p100 processing and a RelB competition mechanism setting signaling output.

    Evidence Cryo-EM and X-ray structures with hexamer-surface mutagenesis; co-IP mapping of RelB/NIK/IKK1/p100 complex

    PMID:27678221 PMID:27851956

    Open questions at the time
    • How hexamer assembly is regulated in cells unknown
    • Structure of the full active signalsome not resolved
  20. 2018 Medium

    Identified a specific IKK-alpha substrate (DCNL5 Ser-41) in innate immunity and demonstrated a redundant NF-kappaB-independent pro-survival role of the IKK complex against TNF/RIPK1-driven apoptosis.

    Evidence In vitro kinase specificity assays; CRISPR/Cas9n single and double IKK knockouts in human cells

    PMID:29630899 PMID:29958295

    Open questions at the time
    • Functional consequence of DCNL5 phosphorylation incompletely defined
    • Mechanism of IKK restraint on RIPK1 unclear
  21. 2019 High

    Confirmed in vivo kinase-independent IKK-alpha function in osteoarthritic cartilage degradation and established IKK-alpha as a lung epithelial tumor suppressor restraining HIF-1alpha.

    Evidence Inducible chondrocyte knockout DMM model; inducible AT-II knockout carcinogenesis and NSCLC xenografts with transcriptome profiling

    PMID:31222033 PMID:31792060

    Open questions at the time
    • Mechanism by which kinase-dead IKK-alpha drives ECM remodeling unknown
    • Direct link between IKK-alpha and HIF-1alpha regulation undefined
  22. 2021 High

    Dissected cell-type-specific in vivo roles and clarified NIK-IKK coupling, showing IKK-alpha in lymphatic endothelium drives lymph node formation while NIK can activate IKK2 independently of IKK1's enzymatic function.

    Evidence Tissue-specific conditional knockouts; NIK interaction-domain knock-in mice with co-IP and pathway assays

    PMID:34810256 PMID:41060807

    Open questions at the time
    • Distinct effectors in LEC vs hematopoietic compartments unidentified
    • Structural basis of NIK-IKK2 independent activation unresolved
  23. 2022 Low

    Suggested post-translational regulation of IKK-alpha by O-GlcNAc-modified NLRX1 to limit IL-1beta in macrophages.

    Evidence Co-IP, colocalization, OGT inhibition, IL-1beta measurement

    PMID:35513753

    Open questions at the time
    • Single co-IP study without reciprocal validation
    • Direct effect of NLRX1 binding on IKK-alpha kinase activity not shown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How nuclear IKK-alpha is selectively recruited to specific gene loci, and the molecular basis of its kinase-independent structural functions in development and ECM remodeling, remain unresolved.
  • No defined targeting mechanism for nuclear/chromatin IKK-alpha
  • Kinase-independent effector partners largely unidentified
  • Full active-signalsome structure not determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 6 GO:0140096 catalytic activity, acting on a protein 5 GO:0140110 transcription regulator activity 5 GO:0140657 ATP-dependent activity 2
Localization
GO:0005634 nucleus 6 GO:0005829 cytosol 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-1266738 Developmental Biology 6 R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 5 R-HSA-1643685 Disease 3 R-HSA-4839726 Chromatin organization 3 R-HSA-5357801 Programmed Cell Death 2
Partners
DDX3XIKBKBMAP3K14NEMONFKB2RELBSMAD3VAV1
Complex memberships
IKK signalsome

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 CHUK (IKK-alpha) was identified as a new protein containing a serine-threonine kinase catalytic domain at the N-terminus, a leucine zipper-like amphipathic alpha-helix in the middle, and a helix-loop-helix domain at the C-terminus, suggesting its kinase activity may be targeted to HLH and/or leucine zipper transcription factors. cDNA cloning and sequence analysis of murine CHUK Cellular & molecular biology research Medium 8777433
1997 IKK-1 (IKK-alpha) and IKK-2 are components of a large multiprotein IkappaB kinase (IKK) signalsome complex purified from HeLa cells that phosphorylates IkappaB-alpha and IkappaB-beta in response to cytokine stimulation. Mutant IKK-2 affected RelA nuclear translocation and NF-kappaB-dependent reporter activity, establishing both kinases as essential for NF-kappaB activation. Biochemical purification of the IKK complex from HeLa cells, in vitro kinase assays phosphorylating IkappaB substrates, dominant-negative mutant analysis of NF-kappaB reporter activity Science (New York, N.Y.) High 9346484
1998 NF-kappaB-inducing kinase (NIK) preferentially phosphorylates IKK-alpha over IKK-beta specifically on Ser-176 in the activation loop. A Ser-176-to-Ala mutant cannot be phosphorylated or activated by NIK and acts as a dominant negative inhibitor of IL-1- and TNF-induced NF-kappaB activation; a Ser-176-to-Glu mutant is constitutively active. In vitro kinase assay, site-directed mutagenesis (S176A and S176E), dominant-negative inhibition of NF-kappaB activation Proceedings of the National Academy of Sciences of the United States of America High 9520446
1999 Both IKK-alpha and IKK-beta are activated by hematopoietic progenitor kinase-1 (HPK1) and MEKK1 stress response kinases. IKK-beta phosphorylated IkappaB constitutively in these assays whereas IKK-alpha was not active in the absence of cell stimulation, indicating differential basal activity. In vitro kinase assays, overexpression of HPK1 and MEKK1 upstream activators Oncogene Medium 10523828
1999 IKK-1 (IKK-alpha) homodimer has dramatically lower catalytic efficiency toward IkappaB-alpha peptide substrates (k(cat)/K(m) ~0.02 h-1 uM-1) compared to IKK-2 (17.44 h-1 uM-1), while the IKK1/IKK2 heterodimer exhibits the highest catalytic efficiency (47.50 h-1 uM-1). The C-terminus of IkappaB-alpha activates the multisubunit IKK complex through subunits other than IKK-2. Recombinant protein expression (baculovirus), purification, and kinetic analysis of homodimers vs. heterodimer; peptide substrate kinetics The Journal of biological chemistry High 10593898 10823818
2000 IKK1 and IKK2 double-knockout mouse embryo fibroblasts completely lack NF-kappaB activity in response to all tested inducers, and double-deficient embryos lose NF-kappaB-lacZ reporter expression in vascular endothelial cells, establishing that IKK1 and IKK2 are together essential for NF-kappaB activation in vivo. Genetic knockout (IKK1-/- / IKK2-/- double-deficient mice), NF-kappaB reporter (kappaB-lacZ transgene), MEF stimulation assays Genes & development High 10898787
2002 IKK-alpha homodimers contain non-equivalent active sites: ADP and a peptide inhibitor show differential potency against IkappaBalpha phosphorylation vs. autophosphorylation reactions. The phosphorylation state of the activation loop (S176/S180) affects active site conformation, and autophosphorylation within the homodimer is intramolecular. Recombinant baculovirus-expressed homodimers, enzyme kinetics, inhibitor analysis, S176E/S180E mutant comparison Biochemical and biophysical research communications Medium 12054687
2003 Vav-1 constitutively associates with IKK-alpha (but not IKK-beta) in Jurkat and primary CD4+ T cells via their helix-loop-helix domains. CD28 engagement increases Vav-1-associated IKK-alpha kinase activity, and both IKK-alpha and Vav-1 augment CD28-induced NF-kappaB activation. Vav-1 and IKK-alpha (but not IKK-beta) colocalize at the membrane upon CD28 stimulation. Co-immunoprecipitation, in vitro kinase assay, NF-kappaB reporter assay, confocal microscopy Journal of immunology (Baltimore, Md. : 1950) Medium 12626540
2003 EBV LMP1 induces p100/NF-kappaB2 processing to p52 in human lymphoblasts via a NIK/IKKalpha-dependent and IKKbeta/IKKgamma-independent mechanism. IKKalpha knockout MEFs show loss of LMP1-induced MIG and CXCR4 upregulation, while IKKalpha absence hyperinduces MIP-2, TNF-alpha, and I-TAC, indicating IKKalpha's dual role in promoting noncanonical and downmodulating canonical NF-kappaB signaling. Genetic knockout MEFs (IKKalpha KO), dominant-negative IKK constructs, RNA expression analysis, NF-kappaB pathway dissection Proceedings of the National Academy of Sciences of the United States of America High 14691250
2004 IKK-alpha has a dual NF-kappaB-dependent role (cusp formation) and an NF-kappaB-independent role (direction of epithelial invagination vs. evagination in incisor and whisker development) in tooth and ectodermal appendage development in mice. Ikkα mutant mouse analysis, genetic comparison with cIκBαΔN transgenic mice (NF-kappaB blocking), examination of Notch/Wnt/Shh pathway markers Developmental cell High 14960276
2004 IKKalpha, IKKbeta, IKKepsilon, and TBK1 can all phosphorylate p65/RelA at Ser-536. IKKepsilon and TBK1 phosphorylate Ser-536 in vivo and in vitro. Importantly, IKKalpha/beta RNAi knockdown or IKKbeta inhibitor alone could not suppress Ser-536 phosphorylation, suggesting IKK-independent pathways also contribute. RNA interference, pharmacological inhibitors, chromatographic fractionation, in vitro kinase assay, reconstitution in p65-deficient fibroblasts The Journal of biological chemistry Medium 15489227
2005 IKK1 (IKKalpha) knockout macrophages show enhanced NF-kappaB activity due to prolonged IkappaBalpha degradation after pathogen stimulation, caused by uncontrolled IKK2 kinase activity. This reveals IKK1 functions as a checkpoint to control IKK2-mediated IkappaBalpha phosphorylation in innate immunity. IKK1-/- embryonic liver-derived macrophages, NF-kappaB activity assay, IKK2 kinase assay, cytokine secretion measurement Proceedings of the National Academy of Sciences of the United States of America High 16116086
2005 IKKalpha is required for RANK ligand-induced osteoclast formation in vitro but is not required in vivo for osteoclastogenesis, while IKKbeta is required both in vitro and in vivo. This establishes distinct and non-redundant roles for IKKalpha and IKKbeta downstream of RANK signaling. Conditional knockout mice (hematopoietic-specific), in vitro osteoclastogenesis assays, inflammation-induced bone loss model The Journal of experimental medicine High 15897281
2006 IKKalpha regulates estrogen-induced cell cycle progression by controlling transcription of the E2F1 gene and E2F1-responsive genes. Estrogen treatment increases association of endogenous IKKalpha with E2F1 on E2F1-bound promoters, and IKKalpha potentiates p300/CBP-associated factor-mediated acetylation of E2F1. siRNA knockdown of IKKalpha, chromatin immunoprecipitation, Co-immunoprecipitation, gene expression analysis The Journal of biological chemistry Medium 16407216
2006 p63 (TAp63 isoform) directly and indirectly transactivates IKKalpha and Ets-1, respectively, in a genetic pathway upstream of IKKalpha during epidermal development. DeltaNp63 upregulates IKKalpha indirectly through GATA-3. Genetic complementation in mice confirmed this p63→IKKalpha epistatic relationship. Molecular analyses (transcriptional assays), genetic complementation in mice, in vivo epistasis Journal of cell science High 17093266
2007 ATM kinase phosphorylates IKK-alpha at Ser-473 in response to cisplatin treatment, causing nuclear accumulation of IKK-alpha, which then stabilizes p73 to promote apoptosis. IKKalpha-deficient MEFs show cisplatin-resistant phenotype. In vitro kinase assay (ATM phosphorylates IKK-alpha), site identification, immunofluorescence colocalization, IKKalpha-deficient MEF functional assay Oncogene Medium 17700524
2007 IKK-alpha mediates chromatin modification on pro-inflammatory gene promoters in response to cigarette smoke: it phosphorylates histone H3 Ser-10 and promotes acetylation of H3 Lys-9 and RelA/p65 Lys-310, leading to sustained transcription of IL-6 and MIP-2. Dominant-negative IKK-alpha reduced CS-induced chromatin modification. Chromatin immunoprecipitation, gain-of-function overexpression, dominant-negative mutant transfection, in vivo mouse lung CS exposure American journal of respiratory cell and molecular biology Medium 18239189
2007 NIK differentially regulates IKK-alpha-mediated activation of IRF3/7 vs. NF-kappaB: IKKalpha-S176E constitutively activates IRF3/7, while IKKalpha-S180E loses the ability to activate IRF3/7, demonstrating that the two NIK-phosphorylation sites on IKKalpha differentially govern its downstream effector functions. Site-directed mutagenesis (S176E, S180E), overexpression, IFN-alpha promoter reporter assay, NF-kappaB reporter assay Molecular immunology Medium 18068231
2007 IKK1/IKKalpha and IKKbeta are both required for S. pneumoniae-induced MUC5AC mucin upregulation via an ERK1-dependent but IkappaBalpha-p65- and p100-p52-independent mechanism, revealing novel NF-kappaB-independent roles for IKKs in innate mucosal defense. Dominant-negative IKK constructs, siRNA knockdown, pathway inhibitors, ERK dependency assays, in vivo mouse model Journal of immunology (Baltimore, Md. : 1950) Medium 17237423
2007 Keratinocyte-specific IKK1 ablation causes impaired epidermal-barrier function and increased transepidermal water loss due to defects in stratum corneum lipid composition and epidermal tight junctions, mediated by deregulation of retinoic acid receptor target genes. IKK1 is recruited to promoters of retinoic acid-regulated genes, indicating a role in RA-regulated transcription. Conditional knockout mice (keratinocyte-specific IKK1 ablation), barrier function assays, chromatin immunoprecipitation, retinoic acid-induced gene expression analysis Nature cell biology High 17351639
2008 BAFF activates Akt and Erk in primary mouse B cells through BAFF-R in an IKK1-dependent manner, establishing IKK1 as a coordinator of multiple BAFF-R-mediated survival signaling pathways beyond NF-kappaB. IKK1 conditional knockout B cells, BAFF stimulation, Akt and Erk phosphorylation assays Proceedings of the National Academy of Sciences of the United States of America High 18713867
2008 Combined conditional ablation of IKK1 and IKK2 (but not each alone) in hepatocytes sensitizes the liver to LPS/TNF-induced failure, revealing redundancy in canonical NF-kappaB signaling. Additionally, combined ablation of IKK1+IKK2 or IKK1+NEMO causes spontaneous fatal cholangitis involving IKK1-specific functions affecting the bile-blood barrier, revealing a novel IKK1-specific function in bile duct integrity. Conditional double-knockout mice (liver-specific), in vivo LPS challenge, histopathology Proceedings of the National Academy of Sciences of the United States of America High 18606991
2008 IKKalpha/beta-phosphorylated IkappaBalpha plays a role in axon outgrowth and axon initial segment (AIS) development in hippocampal neurons. Inhibition of IkappaBalpha phosphorylation by IKKs impedes axon outgrowth and impairs localization of ankyrin G and voltage-gated sodium channels at the AIS. Pharmacological inhibition of IKK kinase activity in cultured hippocampal neurons, immunofluorescence for AIS markers Molecular and cellular neurosciences Low 18321726
2010 The L. monocytogenes secreted protein InlC directly interacts with IKKalpha and impairs IkappaB phosphorylation and degradation normally induced by TNF-alpha, thus dampening host NF-kappaB-dependent innate immune responses during infection. Protein-protein interaction assay (direct binding), infection assays with WT vs. inlC-deletion mutant, cytokine measurement, mouse peritonitis model Proceedings of the National Academy of Sciences of the United States of America High 20855622
2010 IKKalpha is necessary for TGFbeta-SMAD-mediated epithelial-mesenchymal transition (EMT) in Panc1 cells, independently of NF-kappaB. IKKalpha interacts with SMAD3 and controls SMAD complex formation on DNA to regulate transcription of SNAIL and SLUG genes. IKKalpha siRNA knockdown, Co-immunoprecipitation of IKKalpha with SMAD3, chromatin immunoprecipitation, gene expression analysis in Panc1 and MDA-MB231 cells Journal of cell science Medium 21081648
2010 Loss of CHUK (IKKalpha) causes a lethal autosomal recessive fetal syndrome with severe craniofacial and limb malformations in humans, confirming IKKalpha is essential for skin epidermis and ectodermal derivative development. Human genetics (identification of point mutation), candidate-gene analysis, gene-expression arrays in affected fetuses The New England journal of medicine Medium 20961246
2010 In zebrafish, the maternal effect gene poky/chuk/ikk1 is required for EVL differentiation via its kinase activity but not via its HLH domain, in contrast to the mouse where the HLH domain is important, demonstrating conservation of the requirement for Ikk1 in epidermal differentiation with divergent molecular mechanisms. Zebrafish genetic (poky mutant), kinase-dead and HLH-domain mutant rescue experiments, cell cycle and differentiation marker analysis Developmental biology Medium 20692251
2011 Nuclear IKKalpha is present in resting CD4+ T cells and upon Th17 differentiation selectively associates with the Il17a gene locus to promote histone H3 phosphorylation and transcriptional activation of IL-17a in an NF-kappaB-independent manner. Chromatin immunoprecipitation (IKKalpha at Il17a locus), non-activatable IKKalpha knock-in T cells, Th17 differentiation assay, histone modification analysis The Journal of experimental medicine High 21402739
2011 IKK1 inactivation in keratinocytes results in increased p63 expression and repression of Notch signaling. Forced expression of the Notch1 intracellular domain (NICD) partially rescues the differentiation defect of IKK1-/- keratinocytes, placing IKK1 upstream of Notch in epidermal differentiation. Ikk1 genetic inactivation in keratinocytes, NICD overexpression rescue, p63 RNAi knockdown, gene expression analysis The American journal of pathology Medium 21435444
2013 IKKalpha acts independent of its kinase activity to drive chondrocyte hypertrophic differentiation. IKKalpha positively modulates ECM remodeling via multiple downstream targets including MMP-10 and TIMP-3, to maintain maximal MMP-13 collagenase activity. Differentiation of IKKalpha-deficient chondrocytes was rescued by a kinase-dead IKKalpha mutant. Cre-lox conditional IKKalpha knockout chondrocytes, kinase-dead mutant rescue, mRNA profiling, immunoblotting, MMP activity assays PloS one High 24023802
2013 HCV via its 3' UTR interacts with DDX3X to activate IKK-alpha, which translocates to the nucleus and induces a CBP/p300-mediated transcriptional program involving SREBPs to upregulate lipogenic genes and enhance lipid droplet formation for viral assembly, independently of NF-kappaB. siRNA knockdown, chemical inhibitors of IKK-alpha, RNA-protein interaction, nuclear translocation assay, lipid droplet imaging, SREBP transcriptional assay Nature medicine High 23708292
2014 Survivin-2B stabilizes IKK-alpha in the nucleus of NB4 cells; decreased survivin-2B leads to reduced nuclear IKK-alpha, which reduces P73 levels and consequently reduces UVRAG expression, switching protective autophagy to apoptosis. Co-immunoprecipitation (survivin-2B/IKK-alpha interaction in nucleus), nuclear fractionation, gene knockdown, in vivo tumor model Cell death & disease Medium 24556686
2015 Upon HCV infection, DDX3X and IKK-alpha redistribute to stress granules (SGs) upon interaction with the HCV 3' UTR. Subsequently, IKK-alpha translocates to the nucleus while DDX3X and SG proteins redistribute to lipid droplet surfaces. Multiple HCV nonstructural proteins colocalize with DDX3X near SGs and LDs. Systematic imaging (live cell and fixed), biochemical fractionation, co-immunoprecipitation, siRNA knockdown of DDX3X and SG components Journal of virology Medium 25740981
2016 X-ray crystal structure and cryo-EM structure of human IKK1 revealed dimeric and hexameric (trimer of dimers) forms. A surface critical for hexamer formation is essential for IKK1-dependent cellular p100-to-p52 processing (non-canonical NF-kappaB signaling), and this surface is divergent from IKK2, providing structural basis for distinct signaling by the two kinases. Single-particle cryo-EM, X-ray crystallography, mutagenesis of hexamer-forming surface, p100 processing assay in cells Cell reports High 27851956
2016 RelB competes with the NIK:IKK1 complex for binding to a shared region of p100 within a transitional complex containing RelB, NIK, IKK1, and p100. This competition modulates the balance between p100 processing to p52 (generating active RelB:p52) and protection of p100 as part of the kappaBsome, controlling non-canonical NF-kappaB signaling output. Co-immunoprecipitation mapping interaction domains, p100 processing assays, analysis of kappaBsome formation Science signaling Medium 27678221
2018 DCNL5 is directly phosphorylated by IKK-alpha (but not IKK-beta) on Ser-41 upon Toll-like receptor activation, identifying DCNL5 as a specific IKK-alpha substrate in innate immune signaling and the first DCNL member known to be regulated by kinase-mediated phosphorylation. In vitro kinase assay (IKKalpha vs. IKKbeta specificity), phosphorylation site mapping (S41), TLR stimulation assays PloS one Medium 29958295
2018 IKK1/IKK2 double-deficient human cells (generated by CRISPR/Cas9n) show increased TNF-induced apoptosis mediated via RIPK1 in a predominantly apoptotic manner, independently of NF-kappaB RelA. Single IKK1 or IKK2 deficiency does not increase cell death, demonstrating a redundant, NF-kappaB-independent pro-survival function of the IKK complex. CRISPR/Cas9n knockout of IKK1, IKK2, IKK1/2 double, and RELA; caspase-3 activation, Annexin V binding, RIPK1 inhibition Biochimica et biophysica acta. Molecular cell research Medium 29630899
2019 Inducible IKKalpha knockout in adult chondrocytes reduces cartilage degradation, collagenase activity, and hypertrophy-like features in the destabilization of medial meniscus (DMM) mouse model of post-traumatic OA, confirming an in vivo kinase-independent role for IKKalpha in OA-associated cartilage degradation. Tamoxifen-inducible conditional knockout (AcanCreERT2/+; IKKαf/f mice), DMM surgical OA model, histopathology, collagenase activity assays Scientific reports High 31222033
2019 IKKalpha/CHUK acts as a tumor suppressor in lung epithelial cells: its loss in AT-II cells increases lung adenoma number and size after chemical carcinogen treatment, and IKKalpha knockdown in human NSCLC lines enhances xenograft tumor growth associated with upregulation of activated HIF-1alpha under hypoxia. Tamoxifen-inducible conditional IKKalpha knockout in AT-II cells, urethane carcinogenesis model, human NSCLC xenografts, transcriptome profiling, HIF-1alpha protein analysis Life science alliance High 31792060
2021 IKK-alpha in lymphatic endothelial cells (LECs) is absolutely essential for lymph node formation, while IKK-alpha in hematopoietic cells (but not LECs) is required for mature B cell homeostasis. These two functions are mediated by distinct IKK-alpha-expressing cell populations. Tissue-specific conditional knockout mice (Tie2-cre, Cdh5-cre, LEC-specific Lyve1-cre, hematopoietic-specific), analysis of lymph node formation and B cell numbers Proceedings of the National Academy of Sciences of the United States of America High 34810256
2021 NIK, by binding to IKK1, also associates with IKK2 and NEMO, allowing NIK to direct phosphorylation of IKK2 independently of IKK1's enzymatic function. IKK2 activation is maintained even when NIK's interaction with IKK1/NF-kappaB2 is compromised by specific NIK mutation, demonstrating that NIK-IKK1 and NIK-IKK2 activation pathways are not strictly coupled. NIK interaction-domain mutant knock-in mice, IKK1/IKK2 co-immunoprecipitation with NIK, NF-kappaB pathway activation assays Cell reports High 41060807
2022 O-GlcNAc-modified NLRX1 interacts with IKK-alpha in M1 macrophages; elevated O-GlcNAcylation enhances the NLRX1/IKK-alpha interaction, and this enhanced interaction reduces IL-1beta expression, suggesting IKK-alpha is regulated by NLRX1 in a post-translational modification-dependent manner. Co-immunoprecipitation, confocal colocalization, ubiquitination assay, OGT inhibitor treatment, IL-1beta expression measurement In vitro cellular & developmental biology. Animal Low 35513753

Source papers

Stage 0 corpus · 91 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF-kappaB activation. Science (New York, N.Y.) 1786 9346484
1998 NF-kappaB-inducing kinase activates IKK-alpha by phosphorylation of Ser-176. Proceedings of the National Academy of Sciences of the United States of America 451 9520446
2012 The microRNA miR-23b suppresses IL-17-associated autoimmune inflammation by targeting TAB2, TAB3 and IKK-α. Nature medicine 372 22660635
2004 Constitutive and interleukin-1-inducible phosphorylation of p65 NF-{kappa}B at serine 536 is mediated by multiple protein kinases including I{kappa}B kinase (IKK)-{alpha}, IKK{beta}, IKK{epsilon}, TRAF family member-associated (TANK)-binding kinase 1 (TBK1), and an unknown kinase and couples p65 to TATA-binding protein-associated factor II31-mediated interleukin-8 transcription. The Journal of biological chemistry 317 15489227
2001 Activation of NF-kappa B by nontypeable Hemophilus influenzae is mediated by toll-like receptor 2-TAK1-dependent NIK-IKK alpha /beta-I kappa B alpha and MKK3/6-p38 MAP kinase signaling pathways in epithelial cells. Proceedings of the National Academy of Sciences of the United States of America 228 11438700
2005 I{kappa}B kinase (IKK){beta}, but not IKK{alpha}, is a critical mediator of osteoclast survival and is required for inflammation-induced bone loss. The Journal of experimental medicine 209 15897281
2016 TNF-α Modulation of Intestinal Tight Junction Permeability Is Mediated by NIK/IKK-α Axis Activation of the Canonical NF-κB Pathway. The American journal of pathology 170 26948423
2013 Hepatitis C virus infection activates an innate pathway involving IKK-α in lipogenesis and viral assembly. Nature medicine 158 23708292
2000 Complete lack of NF-kappaB activity in IKK1 and IKK2 double-deficient mice: additional defect in neurulation. Genes & development 155 10898787
1998 Role of IKK1 and IKK2 in lipopolysaccharide signaling in human monocytic cells. The Journal of biological chemistry 153 9804806
2003 Epstein-Barr virus latent infection membrane protein 1 TRAF-binding site induces NIK/IKK alpha-dependent noncanonical NF-kappaB activation. Proceedings of the National Academy of Sciences of the United States of America 146 14691250
2010 Activation of PI3K/Akt/IKK-alpha/NF-kappaB signaling pathway is required for the apoptosis-evasion in human salivary adenoid cystic carcinoma: its inhibition by quercetin. Apoptosis : an international journal on programmed cell death 122 20386985
2010 IKK(α) controls canonical TGF(ß)-SMAD signaling to regulate genes expressing SNAIL and SLUG during EMT in panc1 cells. Journal of cell science 111 21081648
2006 p63 is upstream of IKK alpha in epidermal development. Journal of cell science 110 17093266
2005 Enhanced NF-kappaB activation and cellular function in macrophages lacking IkappaB kinase 1 (IKK1). Proceedings of the National Academy of Sciences of the United States of America 108 16116086
2010 The Listeria monocytogenes InlC protein interferes with innate immune responses by targeting the I{kappa}B kinase subunit IKK{alpha}. Proceedings of the National Academy of Sciences of the United States of America 93 20855622
2008 IKK1 and IKK2 cooperate to maintain bile duct integrity in the liver. Proceedings of the National Academy of Sciences of the United States of America 79 18606991
2007 Normal epidermal differentiation but impaired skin-barrier formation upon keratinocyte-restricted IKK1 ablation. Nature cell biology 77 17351639
2008 IKK alpha causes chromatin modification on pro-inflammatory genes by cigarette smoke in mouse lung. American journal of respiratory cell and molecular biology 75 18239189
2008 BAFF activates Akt and Erk through BAFF-R in an IKK1-dependent manner in primary mouse B cells. Proceedings of the National Academy of Sciences of the United States of America 74 18713867
1995 CHUK, a new member of the helix-loop-helix and leucine zipper families of interacting proteins, contains a serine-threonine kinase catalytic domain. Cellular & molecular biology research 68 8777433
2018 Inhibitory-κB Kinase (IKK) α and Nuclear Factor-κB (NFκB)-Inducing Kinase (NIK) as Anti-Cancer Drug Targets. Cells 66 30347849
2007 A novel role for IkappaB kinase (IKK) alpha and IKKbeta in ERK-dependent up-regulation of MUC5AC mucin transcription by Streptococcus pneumoniae. Journal of immunology (Baltimore, Md. : 1950) 65 17237423
2004 A dual role for Ikk alpha in tooth development. Developmental cell 63 14960276
2015 Dynamic Interaction of Stress Granules, DDX3X, and IKK-α Mediates Multiple Functions in Hepatitis C Virus Infection. Journal of virology 60 25740981
2006 Validation of the anti-inflammatory properties of small-molecule IkappaB Kinase (IKK)-2 inhibitors by comparison with adenoviral-mediated delivery of dominant-negative IKK1 and IKK2 in human airways smooth muscle. Molecular pharmacology 60 16687566
2000 Characterization of the recombinant IKK1/IKK2 heterodimer. Mechanisms regulating kinase activity. The Journal of biological chemistry 57 10823818
2007 The discovery of 2-amino-3,5-diarylbenzamide inhibitors of IKK-alpha and IKK-beta kinases. Bioorganic & medicinal chemistry letters 55 17502144
2010 poky/chuk/ikk1 is required for differentiation of the zebrafish embryonic epidermis. Developmental biology 53 20692251
2010 Mutant CHUK and severe fetal encasement malformation. The New England journal of medicine 53 20961246
2016 Structural Basis for the Activation of IKK1/α. Cell reports 50 27851956
2007 ATM-dependent nuclear accumulation of IKK-alpha plays an important role in the regulation of p73-mediated apoptosis in response to cisplatin. Oncogene 48 17700524
2011 Transcriptional regulation of the Th17 immune response by IKK(alpha). The Journal of experimental medicine 46 21402739
2008 New role of IKK alpha/beta phosphorylated I kappa B alpha in axon outgrowth and axon initial segment development. Molecular and cellular neurosciences 46 18321726
2013 The ERLIN1-CHUK-CWF19L1 gene cluster influences liver fat deposition and hepatic inflammation in the NHLBI Family Heart Study. Atherosclerosis 43 23477746
2003 Vav-1 and the IKK alpha subunit of I kappa B kinase functionally associate to induce NF-kappa B activation in response to CD28 engagement. Journal of immunology (Baltimore, Md. : 1950) 43 12626540
2013 IKKα/CHUK regulates extracellular matrix remodeling independent of its kinase activity to facilitate articular chondrocyte differentiation. PloS one 42 24023802
1999 Hematopoietic progenitor kinase-1 (HPK1) stress response signaling pathway activates IkappaB kinases (IKK-alpha/beta) and IKK-beta is a developmentally regulated protein kinase. Oncogene 40 10523828
2006 IKK alpha regulates estrogen-induced cell cycle progression by modulating E2F1 expression. The Journal of biological chemistry 37 16407216
2021 Attribution of NF-κB Activity to CHUK/IKKα-Involved Carcinogenesis. Cancers 36 33808757
2007 Differential regulation of IKK alpha-mediated activation of IRF3/7 by NIK. Molecular immunology 35 18068231
2016 The NF-κB subunit RelB controls p100 processing by competing with the kinases NIK and IKK1 for binding to p100. Science signaling 27 27678221
2018 miRNA-1290 Promotes Aggressiveness in Pancreatic Ductal Adenocarcinoma by Targeting IKK1. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 25 30463064
2018 Participation of the IKK-α/β complex in the inhibition of the TNF-α/NF-κB pathway by glycine: Possible involvement of a membrane receptor specific to adipocytes. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 24 29550635
1995 CHUK, a conserved helix-loop-helix ubiquitous kinase, maps to human chromosome 10 and mouse chromosome 19. Genomics 24 7558004
2006 Neuroprotective effect of a chuk-me-sun-dan on neurons from ischemic damage and neuronal cell toxicity. Neurochemical research 22 16474991
2018 IL-17A-associated IKK-α signaling induced TSLP production in epithelial cells of COPD patients. Experimental & molecular medicine 21 30291224
2021 D-Limonene Is a Potential Monoterpene to Inhibit PI3K/Akt/IKK-α/NF-κB p65 Signaling Pathway in Coronavirus Disease 2019 Pulmonary Fibrosis. Frontiers in medicine 20 33768100
2020 Cantharidin-induced acute hepatotoxicity: the role of TNF-α, IKK-α, Bcl-2, Bax and caspase3. Journal of applied toxicology : JAT 20 32627230
2014 Survivin-2B promotes autophagy by accumulating IKK alpha in the nucleus of selenite-treated NB4 cells. Cell death & disease 19 24556686
2006 Use of Chuk as an internal standard suitable for quantitative RT-PCR in mouse preimplantation embryos. Reproductive biomedicine online 19 16984773
2013 Classical NF-κB activation impairs skeletal muscle oxidative phenotype by reducing IKK-α expression. Biochimica et biophysica acta 18 24215713
2019 Inducible knockout of CHUK/IKKα in adult chondrocytes reduces progression of cartilage degradation in a surgical model of osteoarthritis. Scientific reports 15 31222033
2019 miR‑379 inhibits cell proliferation and epithelial‑mesenchymal transition by targeting CHUK through the NF‑κB pathway in non‑small cell lung cancer. Molecular medicine reports 14 31173238
2002 Characterization of the bovine IkappaB kinases (IKK)alpha and IKKbeta, the regulatory subunit NEMO and their substrate IkappaBalpha. Gene 14 12459277
1999 Peptides corresponding to the N and C termini of IkappaB-alpha, -beta, and -epsilon as probes of the two catalytic subunits of IkappaB kinase, IKK-1 and IKK-2. The Journal of biological chemistry 13 10593898
2022 The long non-coding RNA SNHG1 attenuates chondrocyte apoptosis and inflammation via the miR-195/IKK-α axis. Cell and tissue banking 12 35796880
2019 Polymorphisms and genetic effects of PRLR, MOGAT1, MINPP1 and CHUK genes on milk fatty acid traits in Chinese Holstein. BMC genetics 12 31419940
2018 IKK1/2 protect human cells from TNF-mediated RIPK1-dependent apoptosis in an NF-κB-independent manner. Biochimica et biophysica acta. Molecular cell research 12 29630899
2022 Scallop IKK1 Responds to Bacterial and Virus-Related Pathogen Stimulation and Interacts With MyD88 Adaptor of Toll-Like Receptor Pathway Signaling. Frontiers in immunology 9 35422814
2019 CHUK/IKK-α loss in lung epithelial cells enhances NSCLC growth associated with HIF up-regulation. Life science alliance 9 31792060
2017 Identification of a de novo variant in CHUK in a patient with an EEC/AEC syndrome-like phenotype and hypogammaglobulinemia. American journal of medical genetics. Part A 9 28513979
2024 GRP78 recognizes EV-F 3D protein and activates NF-κB to repress virus replication by interacting with CHUK/IKBKB. Journal of virology 8 38775480
2021 MiRNA-223-3p Affects Mantle Cell Lymphoma Development by Regulating the CHUK/NF-ƘB2 Signaling Pathway. OncoTargets and therapy 8 33688203
2018 The NEDD8 E3 ligase DCNL5 is phosphorylated by IKK alpha during Toll-like receptor activation. PloS one 8 29958295
2012 Knockdown of IKK1/2 promotes differentiation of mouse embryonic stem cells into neuroectoderm at the expense of mesoderm. Stem cell reviews and reports 8 22833419
2021 miRNA-223-3p modulates ibrutinib resistance through regulation of the CHUK/Nf-κb signaling pathway in mantle cell lymphoma. Experimental hematology 7 34474146
2018 Novel heterozygous pathogenic variants in CHUK in a patient with AEC-like phenotype, immune deficiencies and 1q21.1 microdeletion syndrome: a case report. BMC medical genetics 7 29523099
2011 IKK1 control of epidermal differentiation is modulated by notch signaling. The American journal of pathology 7 21435444
2002 The catalytic subunits of IkappaB kinase, IKK-1 and IKK-2, contain non-equivalent active sites when expressed as homodimers. Biochemical and biophysical research communications 7 12054687
2023 IKK1 aggravates ischemia-reperfusion kidney injury by promoting the differentiation of effector T cells. Cellular and molecular life sciences : CMLS 6 37074502
2022 The interaction of O-GlcNAc-modified NLRX1 and IKK-α modulates IL-1β expression in M1 macrophages. In vitro cellular & developmental biology. Animal 6 35513753
2005 Neuroprotective effect of Chuk-Me-Sun-Dan on NMDA- and AMPA-evoked nitric oxide synthase activity in mouse brain. Immunopharmacology and immunotoxicology 6 16237959
2001 IKK alpha on center stage. Science's STKE : signal transduction knowledge environment 6 11698579
2022 ATM/IKK alpha axis regulates the crosstalk between autophagy and apoptosis in selenite-treated Jurkat cells. Chemico-biological interactions 5 36113632
2022 Spatial expression of IKK-alpha is associated with a differential mutational landscape and survival in primary colorectal cancer. British journal of cancer 4 35173303
2021 Association of CHUK gene polymorphism and ischemic stroke in the Han Chinese population. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 4 33992196
2013 Silencing of the cell cycle checkpoint gene 14-3-3σ in basal cell carcinomas correlates with reduced expression of IKK-α. Journal of the European Academy of Dermatology and Venereology : JEADV 4 24219383
2025 Delivery of miR-26a-5p by Subcutaneous Adipose Tissue-Derived Extracellular Vesicles Alleviates Acute Lung Injury in Mice Through CHUK/NF-κB Pathway. International journal of nanomedicine 3 40370804
2014 RNAi-mediated knockdown of IKK1 in transgenic mice using a transgenic construct containing the human H1 promoter. TheScientificWorldJournal 3 24523631
2012 Models for predicting IKKA and IKKB blockade. Journal of chemical information and modeling 3 23157456
2021 A naturally derived small molecule NDSM253 inhibits IKK1 to suppress inflammation response and promote bone healing after fracture. American journal of translational research 2 33527006
2021 Lymph node formation and B cell homeostasis require IKK-α in distinct endothelial cell-derived compartments. Proceedings of the National Academy of Sciences of the United States of America 2 34810256
2025 Assessment of Unexpected (Non-ABO) Red Blood Cell Antibodies and Their Associated Clinical Conditions Among Patients and Blood Donors Attending University Teaching Hospital of Kigali (CHUK) and Rwanda Blood Transfusion Division. Advances in hematology 1 40151361
2024 Higher expression of BRCA1, and CHUK and lower expression of NFKBIA, ESR1, PIK3R1, and PPARG in HAM/TSP compared to ATLL, a diverse pathological consequence. Indian journal of pathology & microbiology 1 38847220
2021 A Kinase Assay for Measuring the Activity of the NIK-IKK1 Complex Induced via the Noncanonical NF-κB Pathway. Methods in molecular biology (Clifton, N.J.) 1 34236638
2018 A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α. Journal of visualized experiments : JoVE 1 30451218
2008 [Effect of Kuijieling decoction on proteins expression of IKK-alpha in colonic mucosa of ulcerative colitis model rats]. Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials 1 18973019
2026 Hsa-miR-5585-3p regulates the NLRP3 activation and the expression of cytokines through CHUK in a cellular model of diabetic kidney disease. BMC endocrine disorders 0 42135680
2025 Limited activation interdependence and differing patterns of the in vivo effects of IKK1 and IKK2 downstream of NIK. Cell reports 0 41060807
2024 Cimicifugoside H-2 as an Inhibitor of IKK1/Alpha: A Molecular Docking and Dynamic Simulation Study. Biomolecules 0 39062574

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