AC T00950
XX
ID T00950
XX
DT 23.06.1993 (created); ewi.
DT 27.01.2015 (updated); spk.
CO Copyright (C), QIAGEN.
XX
FA IkappaB-alpha
XX
SY human inhibitor kappaB-alpha; I-kappa-B-alpha; IkappaB-alpha; IKBA; MAD-3; MAD3; NF-kappa-B inhibitor alpha; NFKBI; NFKBIA.
XX
OS human, Homo sapiens
OC eukaryota; animalia; metazoa; chordata; vertebrata; tetrapoda; mammalia; eutheria; primates
XX
GE G002981 NFKBIA; HGNC: NFKBIA.
XX
CL C0020; Rel; 6.1.2.1.1.
XX
SF ankyrin repeats interact with, e. g., c-Rel, but the PEST sequence is responsible for inhibition of DNA-binding [20];
XX
CP (monocytes).
XX
FF S-Adenosylmethionine (SAMe) treatment decreases the protein expression in HepG2 cells [70];
FF Pretreatment of THP-1 cells with V5 tagged human ST2 induces the degradation of IkappaB-alpha following the LPS stimulation [53];
FF inhibits NF-kappaB (not c-Rel or v-Rel) through the RelA (p65) subunit [11] [4] [1];
FF masking of the nuclear localization signals of both the RelA and the NF-kappaB1 (p50) subunit [7] [22];
FF retains NF-kappaB in the cytoplasm, but also may dissociate it from the DNA [1];
FF zeta-PKC binds to and activates a 50-kDa IkappaB kinase [17];
FF dsRNA-activates p68 protein kinase (PKR) directly phosphorylates IkappaB-alpha and activates NF-kappaB [26];
FF one upstream kinase is Raf-1 [23];
FF external triggers of IkappaB phosphorylation and inactivation are TNF-alpha or IL-1 [14];
FF phosphorylation and rapid proteolytic degradation triggered by HTLV-I Tax [13];
FF phosphorylated IkappaB-alpha still binds to NF-kappaB but is tagged for rapid degradation by a chymotrypsin-like activity of the proteasome [18];
FF in B cells, constitutive phosphorylation of IkappaB-alpha may contribute to constitutive NF-kappaB activity in these cells [9];
FF in other cells, IkappaB is subjected to a constant low-level turnover providing a very low concentration of active NF-kappaB [25];
FF in addition to IkappaB phosphorylation, a dephosphorylation step is also required for IkappaB inactivation which is mediated by the calcium-calmodulin-dependent protein phosphatase calcineurin [15];
FF TNF signalling to activate NF-kappaB by IkappaB degradation involves sphingomyelinase [16];
FF expression of the IkappaB-alpha gene is enhanced by NF-kappaB [6] [12] [22] [24] [25];
FF also, glucocorticoids induce IkappaB synthesis and thus decrease the concentration of active NF-kappaB [21] [27];
FF IkappaB-alpha is rapidly induced following monocyte adherence due to a posttranscriptional control mechanism [19] [2];
FF enhanced cAMP levels may cause a retarded degradation of IkappaB-alpha in T cells [10];
XX
IN T02765 ERR1; human, Homo sapiens.
IN T04106 HDAC1; human, Homo sapiens.
IN T04110 HDAC3; human, Homo sapiens.
IN T01924 NF-kappaB1-isoform1; mouse, Mus musculus.
IN T00593 NF-kappaB1-p50; human, Homo sapiens.
IN T01925 NF-kappaB1; human, Homo sapiens.
IN T00587 NF-kappaB; rat, Rattus norvegicus.
IN T00588 NF-kappaB; mouse, Mus musculus.
IN T00590 NF-kappaB; human, Homo sapiens.
IN T21984 p300; human, Homo sapiens.
IN T00594 RelA-p65-isoform1; human, Homo sapiens.
IN T00595 RelA-p65; mouse, Mus musculus.
IN T08711 RelA-p65; human, Homo sapiens.
IN T10397 RelA-p65; Mammalia.
IN T00897 v-Rel; REV-T, reticuloendotheliosis virus (strain T).
XX
DR TRANSPATH: MO000019315.
DR UniProtKB: P25963;
XX
RN [1]; RE0000091.
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RA Zabel U., Bauerle P. A.
RT Purified human IkappaB can rapidly dissociate the complex of the NF-kappaB transcription factor with its cognate DNA
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RA Haskill S., Beg A. A., Tompkins S. M., Morris J. S., Yurochko A. D., Sampson-Johannes A., Mondal K., Ralph P., Baldwin jr A. S.
RT Characterization of an immediate-early gene induced in adherent monocytes that encodes IkappaB-like activity
RL Cell 65:1281-1289 (1991).
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RA Urban M. B., Schreck R., Baeuerle P. A.
RT NF-kappaB contacts DNA by a heterodimer of the p50 and p65 subunit
RL EMBO J. 10:1817-1825 (1991).
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RA Urban M. B., Baeuerle P. A.
RT The 65-kD subunit of NF-kappaB is a receptor for IkappaB and a modulator of DNA-binding specificity
RL Genes Dev. 4:1975-1984 (1990).
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RA Ghosh S., Baltimore D.
RT Activation in vitro of NF-kappaB by phosphorylation of its inhibitor IkappaB
RL Nature 344:678-682 (1990).
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RA Bail O. L., Schmidt-Ullrich R., Israel A.
RT Promoter analysis of the gene encoding the IkappaB-alpha/MAD3 inhibitor of NF-kappaB: positive regulation by members of the rel/NF-kappaB family
RL EMBO J. 12:5043-5049 (1993).
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RA Zabel U., Henkel T., dos Santos Silva M., Baeuerle P. A.
RT Nuclear uptake control of NF-kappaB by MAD-3, an IkappB protein present in the nucleus
RL EMBO J. 12:201-211 (1993).
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RA Stein B., Yang M. X.
RT Repression of the interleukin-6 promoter by estrogen receptor is mediated by NF-kappaB and C/EBPbeta
RL Mol. Cell. Biol. 15:4971-4979 (1995).
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RA Naumann M., Scheidereit C.
RT Activation of NF-6B in vivo is regulated by multiple phosphorylations
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RA Neumann M., Grieshammer T., Chuvpilo S., Kneitz B., Lohoff M., Schimpl A., Franza jr B. R., Serfling E.
RT ReIA/p65 is a molecular target for the immunosuppressive action of protein kinase A
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RA Beg A. A., Ruben S. M., Scheinman R. I., Rosen C. A., Baldwin jr A. S.
RT IkappaB interacts with the nuclear localization sequences of the subunits of the NF-kappaB: a mechanism for cytoplasmic retention
RL Genes Dev. 6:1899-1913 (1992).
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RA Scott M. L., Fujita T., Liou H.-C., Nolan G. P., Baltimore D.
RT The p65 subunit of NF-kappaB regulates IkappaB by two distinct mechanisms
RL Genes Dev. 7:1266-1276 (1993).
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RA Sun S.-C., Elwood J., Beraud C., Greene W. C.
RT Human T-cell leukemia virus type I Tax activation of NF-kappaB/Rel involves phosphorylation and degradation of IkappaBalpha and RelA (p65)-mediated induction of the c-rel gene
RL Mol. Cell. Biol. 14:7377-7384 (1994).
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RA Beg A. A., Finco T. S., Nantermet P. V., Baldwin jr A. S.
RT Tumor necrosis factor and interleukin-1 lead to phosphorylation and loss of IkappaBalpha: a mechanism for NF-kappaB activation
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RA Frantz B., Nordby E. C., Bren G., Steffan N., Paya C. V., Kincaid R. L., Tocci M. J., O'Keefe S. J., O'Neill E. A.
RT Calcineurin acts in synergy with PMA to inactivate IkappaB/MAD3, an inhibitor of NF-kappaB
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RA Machleidt T., Wiegmann K., Henkel T., Schuetze S., Baeuerle P., Kroenke M.
RT Sphingomyelinase activates proteolytic IkappaB-alpha degradation in a cell-free system
RL J. Biol. Chem. 269:13760-13765 (1994).
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RA Diaz-Meco M. T., Dominguez I., Sanz L., Dent P., Lozano J., Municio M. M., Berra E., Hay R. T., Sturgill T. W., Moscat J.
RT ZetaPKC induces phosphorylation and inactivation of IkappaB-alpha in vitro
RL EMBO J. 13:2842-2848 (1994).
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RA Traenckner E. B.-M., Wilk S., Baeuerle P. A.
RT A proteasome inhibitor prevents activation of NF-kappaB and stabilizes a newly phosphorylated form of IkappaB-alpha that is still bound to NF-kappaB
RL EMBO J. 13:5433-5441 (1994).
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RA Lofquist A. K., Mondal K., Morris J. S., Haskill J. S.
RT Transcription-independent turnover of IkappaBalpha during monocyte adherence: implications for a translational component regulating IkappaBalpha/MAD-3 mRNA levels
RL Mol. Cell. Biol. 15:1737-1746 (1995).
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RA Ernst M. K., Dunn L. L., Rice N. R.
RT The PEST-like sequence of I kappa B alpha is responsible for inhibition of DNA binding but not for cytoplasmatic retention of c-Rel or RelA homodimers
RL Mol. Cell. Biol. 15:872-882 (1995).
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RT Role of transcriptional activation of IkappaBalpha in mediation of immunosuppression of glucocorticoids
RL Science 270:283-286 (1995).
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RT NF-kappaB controls expression of inhibitor IkappaBalpha: Evidence for an inducible autoregulatory pathway
RL Science 259:1912-1915 (1993).
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RA Li S., Sedivy J. M.
RT Raf-1 protein kinase activates the NF-kappaB transcription factor by dissociating the cytoplasmic NF-kappaB-IkappaB complex
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RT Mutual regulation of the transcriptional activator NF-kappaB and its inhibitor, IkappaBalpha
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RT In vivo control of NF-kappaB activation by IkappaBalpha
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RA Kumar A., Haque J., Lacoste J., Hiscott J., Williams B. R. G.
RT Double-stranded RNA-dependent protein kinase activates transcription factor NF-kappaB by phosphorylating IkappaB
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RT Imunosuppression by glucocorticoids: Inhibition of NF-6B activity through induction of I6B synthesis
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RA Whiteside S. T., Epinat J. C., Rice N. R., Israel A.
RT I kappa B epsilon, a novel member of the I kappa B family, controls RelA and cRel NF-kappa B activity.
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RT The NF-kappaB activation pathway: a paradigm in information transfer from membrane to nucleus
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RA Lang V., Janzen J., Fischer G. Z., Soneji Y., Beinke S., Salmeron A., Allen H., Hay R. T., Ben-Neriah Y., Ley S. C.
RT betaTrCP-mediated proteolysis of NF-kappaB1 p105 requires phosphorylation of p105 serines 927 and 932.
RL Mol. Cell. Biol. 23:402-13 (2003).
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RT Cytoplasmic IkappaBalpha increases NF-kappaB-independent transcription through binding to histone deacetylase (HDAC) 1 and HDAC3.
RL J. Biol. Chem. 278:46541-8 (2003).
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RA Jiang X., Takahashi N., Matsui N., Tetsuka T., Okamoto T.
RT The NF-kappa B activation in lymphotoxin beta receptor signaling depends on the phosphorylation of p65 at serine 536.
RL J. Biol. Chem. 278:919-26 (2003).
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RT Inhibitors of protein kinase C (PKC) prevent activated transcription: role of events downstream of NF-kappaB DNA binding.
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RT Identification of signal transduction pathways involved in constitutive NF-kappaB activation in breast cancer cells.
RL Oncogene 21:2066-78 (2002).
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RT NF-{kappa}B is transported into the nucleus by importin {alpha}3 and importin {alpha}4.
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RT Phosphorylation of serine 468 by GSK-3beta negatively regulates basal p65 NF-kappaB activity.
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RT Ceramide activates NFkappaB by inducing the processing of p105.
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RT Fas-induced proteolytic activation and intracellular redistribution of the stress-signaling kinase MEKK1.
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RT Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-kappaB activation.
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RT Hepatitis C virus NS5A and subgenomic replicon activate NF-kappaB via tyrosine phosphorylation of IkappaBalpha and its degradation by calpain protease.
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RA Foy E., Li K., Sumpter R J. r., Loo Y. M., Johnson C. L., Wang C., Fish P. M., Yoneyama M., Fujita T., Lemon S. M., Gale M J. r.
RT Control of antiviral defenses through hepatitis C virus disruption of retinoic acid-inducible gene-I signaling.
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RT Regulation of NF-kappaB signaling by Pin1-dependent prolyl isomerization and ubiquitin-mediated proteolysis of p65/RelA.
RL Mol. Cell 12:1413-1426 (2003).
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RA Jun J. I., Chung C. W., Lee H. J., Pyo J. O., Lee K. N., Kim N. S., Kim Y. S., Yoo H. S., Lee T. H., Kim E., Jung Y. K.
RT Role of FLASH in caspase-8-mediated activation of NF-kappaB: dominant-negative function of FLASH mutant in NF-kappaB signaling pathway.
RL Oncogene 24:688-696 (2005).
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RT Breast tumor kinase (protein tyrosine kinase 6) regulates heregulin-induced activation of ERK5 and p38 MAP kinases in breast cancer cells.
RL Cancer Res. 67:4199-4209 (2007).
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RA Castrillo A., Diaz-Guerra M. J., Hortelano S., Martin-Sanz P., Bosca L.
RT Inhibition of IkappaB kinase and IkappaB phosphorylation by 15-deoxy-Delta(12,14)-prostaglandin J(2) in activated murine macrophages.
RL Mol. Cell. Biol. 20:1692-1698 (2000).
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RT Signaling by Toll-like Receptors 8 and 9 Requires Bruton's Tyrosine Kinase.
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RT NIBP, a novel NIK and IKK(beta)-binding protein that enhances NF-(kappa)B activation.
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RT TNAP, a novel repressor of NF-kappaB-inducing kinase, suppresses NF-kappaB activation.
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RT IKKbeta phosphorylates p65 at S468 in transactivaton domain 2.
RL FASEB J. 19:1758-1760 (2005).
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RT MUC1 oncoprotein activates the IkappaB kinase beta complex and constitutive NF-kappaB signalling.
RL Nat. Cell Biol. 9:1419-1427 (2007).
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RT Caspase-4 interacts with TNF receptor-associated factor 6 and mediates lipopolysaccharide-induced NF-kappaB-dependent production of IL-8 and CC chemokine ligand 4 (macrophage-inflammatory protein-1 ).
RL J. Immunol. 179:8480-8490 (2007).
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RT Protein kinase C delta activates IkappaB-kinase alpha to induce the p53 tumor suppressor in response to oxidative stress.
RL Cell. Signal. 19:2088-2097 (2007).
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RT ST2 suppresses IL-6 production via the inhibition of IkappaB degradation induced by the LPS signal in THP-1 cells.
RL Biochem. Biophys. Res. Commun. 341:425-432 (2006).
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RT Tyrosine phosphorylation of MyD88 adapter-like (Mal) is critical for signal transduction and blocked in endotoxin tolerance.
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RT Hypo-phosphorylation leads to nuclear retention of NF-kappaB p65 due to impaired IkappaBalpha gene synthesis.
RL FEBS Lett. 581:5493-5499 (2007).
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RT The tumor suppressor cylindromatosis (CYLD) acts as a negative regulator for toll-like receptor 2 signaling via negative cross-talk with TRAF6 AND TRAF7.
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RT Suppressor of cytokine signaling 1 negatively regulates Toll-like receptor signaling by mediating Mal degradation.
RL Nat. Immunol. 7:148-155 (2006).
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RT A nuclear export signal in the N-terminal regulatory domain of IkappaBalpha controls cytoplasmic localization of inactive NF-kappaB/IkappaBalpha complexes.
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RT Regulation of type 2 nitric oxide synthase by type 1 interferons in macrophages infected with Leishmania major.
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RA Wan F., Anderson D. E., Barnitz R. A., Snow A., Bidere N., Zheng L., Hegde V., Lam L. T., Staudt L. M., Levens D., Deutsch W. A., Lenardo M. J.
RT Ribosomal protein S3: a KH domain subunit in NF-kappaB complexes that mediates selective gene regulation.
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RT Inducible phosphorylation of NF-kappa B p65 at serine 468 by T cell costimulation is mediated by IKK epsilon.
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RT Interleukin-1beta induction of IL-6 is mediated by a novel phosphatidylinositol 3-kinase dependent AKT/Ikappa B kinase alpha pathway targeting activator protein-1.
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RA Lin C. C., Chiang L. L., Lin C. H., Shih C. H., Liao Y. T., Hsu M. J., Chen B. C.
RT Transforming growth factor-beta1 stimulates heme oxygenase-1 expression via the PI3K/Akt and NF-kappaB pathways in human lung epithelial cells.
RL Eur. J. Pharmacol. 560:101-109 (2007).
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RA Solan N. J., Miyoshi H., Carmona E. M., Bren G. D., Paya C. V.
RT RelB cellular regulation and transcriptional activity are regulated by p100.
RL J. Biol. Chem. 277:1405-1418 (2002).
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RA Aneja R. K., Tsung A., Sjodin H., Gefter J. V., Delude R. L., Billiar T. R., Fink M. P.
RT Preconditioning with high mobility group box 1 (HMGB1) induces lipopolysaccharide (LPS) tolerance.
RL J. Leukoc. Biol. 84:1326-1334 (2008).
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RA Saccani S., Pantano S., Natoli G.
RT Modulation of NF-kappaB activity by exchange of dimers.
RL Mol. Cell 11:1563-1574 (2003).
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RA Holden N. S., Squires P. E., Kaur M., Bland R., Jones C. E., Newton R.
RT Phorbol ester-stimulated NF-kappaB-dependent transcription: roles for isoforms of novel protein kinase C.
RL Cell. Signal. 20:1338-1348 (2008).
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RT Variant IL-1 receptor-associated kinase-1 mediates increased NF-kappa B activity.
RL J. Immunol. 179:4125-4134 (2007).
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RT The induction of growth arrest DNA damage-inducible gene 45 beta in human hepatoma cell lines by S-adenosylmethionine.
RL Am. J. Pathol. 171:287-296 (2007).
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RA Jamaluddin M., Wang S., Boldogh I., Tian B., Brasier A. R.
RT TNF-alpha-induced NF-kappaB/RelA Ser(276) phosphorylation and enhanceosome formation is mediated by an ROS-dependent PKAc pathway.
RL Cell. Signal. 19:1419-1433 (2007).
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RA Mandrekar P., Jeliazkova V., Catalano D., Szabo G.
RT Acute alcohol exposure exerts anti-inflammatory effects by inhibiting IkappaB kinase activity and p65 phosphorylation in human monocytes.
RL J. Immunol. 178:7686-7693 (2007).
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