Gene Symbol: Nfkbia
Description: nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha
Alias: AI462015, Nfkbi, NF-kappa-B inhibitor alpha, I(Kappa)B(alpha), I-kappa-B-alpha, I-kappaBalpha, ikB-alpha, ikappaBalpha, nuclear factor of kappa light chain gene enhancer in B-cells inhibitor, alpha, nuclear factor of kappa light polyp gene enhancer in B-cell 1
Species: mouse
Products:     Nfkbia

Top Publications

  1. Baeuerle P, Baltimore D. NF-kappa B: ten years after. Cell. 1996;87:13-20 pubmed
  2. Ghosh S, May M, Kopp E. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol. 1998;16:225-60 pubmed
    ..In this review, we discuss some of these recent findings and their implications for the study of NF-kappa B. ..
  3. Basak S, Kim H, Kearns J, Tergaonkar V, O Dea E, Werner S, et al. A fourth IkappaB protein within the NF-kappaB signaling module. Cell. 2007;128:369-81 pubmed
    Inflammatory NF-kappaB/RelA activation is mediated by the three canonical inhibitors, IkappaBalpha, -beta, and -epsilon...
  4. Goudeau B, Huetz F, Samson S, Di Santo J, Cumano A, Beg A, et al. IkappaBalpha/IkappaBepsilon deficiency reveals that a critical NF-kappaB dosage is required for lymphocyte survival. Proc Natl Acad Sci U S A. 2003;100:15800-5 pubmed
    ..Here, we show that combined IkappaBalpha/IkappaBepsilon deficiency in mice leads to neonatal death, elevated kappaB binding activity, overexpression of ..
  5. Beg A, Sha W, Bronson R, Ghosh S, Baltimore D. Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kappa B. Nature. 1995;376:167-70 pubmed
    ..mice are defective in the tumour necrosis factor (TNF)-mediated induction of messenger RNAs for I kappa B alpha and granulocyte/macrophage colony stimulating factor (GM-CSF), although basal levels of these transcripts are ..
  6. O Dea E, Barken D, Peralta R, Tran K, Werner S, Kearns J, et al. A homeostatic model of IkappaB metabolism to control constitutive NF-kappaB activity. Mol Syst Biol. 2007;3:111 pubmed
  7. Klement J, Rice N, Car B, Abbondanzo S, Powers G, Bhatt P, et al. IkappaBalpha deficiency results in a sustained NF-kappaB response and severe widespread dermatitis in mice. Mol Cell Biol. 1996;16:2341-9 pubmed
    ..NF-kappaB is maintained in an inactive state in the cytoplasm by protein-protein interaction with IkappaBalpha. Upon stimulation, rapid degradation of IkappaBalpha allows nuclear translocation of NF-kappaB...
  8. Wuerzberger Davis S, Chen Y, Yang D, Kearns J, Bates P, Lynch C, et al. Nuclear export of the NF-?B inhibitor I?B? is required for proper B cell and secondary lymphoid tissue formation. Immunity. 2011;34:188-200 pubmed publisher
    ..Thus, I?B? nuclear export is essential to maintain constitutive, canonical, and noncanonical NF-?B activation potentials in mature B cells in vivo...
  9. Thompson J, Phillips R, Erdjument Bromage H, Tempst P, Ghosh S. I kappa B-beta regulates the persistent response in a biphasic activation of NF-kappa B. Cell. 1995;80:573-82 pubmed
    ..Therefore, the overall activation of NF-kappa B consists of two overlapping phases, a transient phase mediated through I kappa B-alpha and a persistent phase mediated through I kappa B-beta. ..

More Information


  1. Lawrence T, Bebien M, Liu G, Nizet V, Karin M. IKKalpha limits macrophage NF-kappaB activation and contributes to the resolution of inflammation. Nature. 2005;434:1138-43 pubmed
    ..Inactivation of IKKalpha in mice enhances inflammation and bacterial clearance. Hence, the two IKK catalytic subunits have evolved opposing but complimentary roles needed for the intricate control of inflammation and innate immunity. ..
  2. Rupec R, Jundt F, Rebholz B, Eckelt B, Weindl G, Herzinger T, et al. Stroma-mediated dysregulation of myelopoiesis in mice lacking I kappa B alpha. Immunity. 2005;22:479-91 pubmed
    ..Newborn mice with a ubiquitous deletion of I kappa B alpha develop a severe hematological disorder characterized by an increase of granulocyte/erythroid/monocyte/..
  3. Rebholz B, Haase I, Eckelt B, Paxian S, Flaig M, Ghoreschi K, et al. Crosstalk between keratinocytes and adaptive immune cells in an IkappaBalpha protein-mediated inflammatory disease of the skin. Immunity. 2007;27:296-307 pubmed
    ..Ubiquitous deficiency of the IkappaBalpha protein (Ikba(Delta)(/Delta)) as well as concomitant deletion of Ikba specifically in keratinocytes and T cells ..
  4. Cheng J, Ryseck R, Attar R, Dambach D, Bravo R. Functional redundancy of the nuclear factor kappa B inhibitors I kappa B alpha and I kappa B beta. J Exp Med. 1998;188:1055-62 pubmed
    ..In an effort to address the functional redundancy of two closely related IkappaB molecules, IkappaBalpha and IkappaBbeta, we generated knock-in mice by replacing the IkappaBalpha gene with the IkappaBbeta gene...
  5. Shih V, Kearns J, Basak S, Savinova O, Ghosh G, Hoffmann A. Kinetic control of negative feedback regulators of NF-kappaB/RelA determines their pathogen- and cytokine-receptor signaling specificity. Proc Natl Acad Sci U S A. 2009;106:9619-24 pubmed publisher
    ..Finally, we found that IkappaB delta provides signaling memory owing to its long half-life; it integrates the inflammatory history of the cell to dampen NF-kappaB responsiveness during sequential stimulation events. ..
  6. Hertlein E, Wang J, Ladner K, Bakkar N, Guttridge D. RelA/p65 regulation of IkappaBbeta. Mol Cell Biol. 2005;25:4956-68 pubmed
    ..In contrast to the defined regulatory interplay between NF-kappaB and IkappaBalpha, much less is known regarding the regulation of IkappaBbeta by NF-kappaB...
  7. Beg A, Sha W, Bronson R, Baltimore D. Constitutive NF-kappa B activation, enhanced granulopoiesis, and neonatal lethality in I kappa B alpha-deficient mice. Genes Dev. 1995;9:2736-46 pubmed
    ..factors belonging to the NF-kappa B family are controlled by inhibitory I kappa B proteins, mainly I kappa B alpha and I kappa B beta...
  8. Werner S, Barken D, Hoffmann A. Stimulus specificity of gene expression programs determined by temporal control of IKK activity. Science. 2005;309:1857-61 pubmed
    ..Thus, the distinct biological responses to LPS and TNFalpha depend on signaling pathway-specific mechanisms that regulate the temporal profile of IKK activity. ..
  9. Hoffmann A, Levchenko A, Scott M, Baltimore D. The IkappaB-NF-kappaB signaling module: temporal control and selective gene activation. Science. 2002;298:1241-5 pubmed
    ..nuclear factor kappaB) is controlled in mammalian cells by three isoforms of NF-kappaB inhibitor protein: IkappaBalpha, -beta, and - epsilon...
  10. Melnick M, Chen H, Zhou Y, Jaskoll T. Embryonic mouse submandibular salivary gland morphogenesis and the TNF/TNF-R1 signal transduction pathway. Anat Rec. 2001;262:318-30 pubmed
    ..The results of these experiments indicate that the TNF/TNF-R1 signal transduction pathway plays an important role in balancing cell proliferation and apoptosis during SMG duct and presumptive acini formation. ..
  11. Schwartz C, Willebrand R, Huber S, Rupec R, WU D, Locksley R, et al. Eosinophil-specific deletion of IκBα in mice reveals a critical role of NF-κB-induced Bcl-xL for inhibition of apoptosis. Blood. 2015;125:3896-904 pubmed publisher
    ..These results suggest that therapeutic strategies targeting Bcl-xL in eosinophils could improve health conditions in allergic inflammatory diseases. ..
  12. Milligan S, Owens M, Grisham M. Inhibition of IkappaB-alpha and IkappaB-beta proteolysis by calpain inhibitor I blocks nitric oxide synthesis. Arch Biochem Biophys. 1996;335:388-95 pubmed
    ..Finally, we have demonstrated that there is a marked difference in the extent of proteolysis of IkappaB-alpha and IkappaB-beta when the ubiquitin-proteasome complex is inhibited with calpain inhibitor I. ..
  13. DeAngelis R, Markiewski M, Taub R, Lambris J. A high-fat diet impairs liver regeneration in C57BL/6 mice through overexpression of the NF-kappaB inhibitor, IkappaBalpha. Hepatology. 2005;42:1148-57 pubmed
    ..The underlying molecular mechanism was associated with increased inhibitor of nuclear factor-kappa B alpha (IkappaBalpha) expression, which inhibited nuclear factor-kappa B (NF-kappaB) activation and induction of its target genes, ..
  14. Ohba Y, Nakaya M, Watari K, Nagasaka A, Kurose H. GRK6 phosphorylates IκBα at Ser(32)/Ser(36) and enhances TNF-α-induced inflammation. Biochem Biophys Res Commun. 2015;461:307-13 pubmed publisher
    ..In summary, our study demonstrates that TNF-α induces GRK6 activation, and GRK6 promotes inflammatory responses through the phosphorylation of IκBα. ..
  15. Papia G, Fan J, Kapus A, Szaszi K, Marshall J, Tawadros P, et al. Altered inhibitory ?B? expression in LPS-stimulated alveolar macrophages following resuscitated hemorrhagic shock. Shock. 2011;35:171-7 pubmed publisher
    ..Together, these effects on the important regulatory molecule I?B in the macrophage may contribute to the heightened inflammatory response observed after S/R. ..
  16. Kim E, Shin H, Kim J, Kim D, Choi Y, Kwon H, et al. ATF3 plays a key role in Kdo2-lipid A-induced TLR4-dependent gene expression via NF-?B activation. PLoS ONE. 2010;5:e14181 pubmed publisher
  17. Molinero L, Miller M, Evaristo C, Alegre M. High TCR stimuli prevent induced regulatory T cell differentiation in a NF-?B-dependent manner. J Immunol. 2011;186:4609-17 pubmed publisher
    ..Thus, NF-?B helps T cells control their differentiation fate in a cell-intrinsic manner and prevents peripheral iTreg development under conditions of high Ag load that may require more vigorous effector T cell responses. ..
  18. Dawn B, Xuan Y, Marian M, Flaherty M, Murphree S, Smith T, et al. Cardiac-specific abrogation of NF- kappa B activation in mice by transdominant expression of a mutant I kappa B alpha. J Mol Cell Cardiol. 2001;33:161-73 pubmed
    ..Phosphorylation of serine residues at positions 32 and 36 is critical for ubiquitination and degradation of I kappa B alpha with consequent migration of NF-kappa B to the nucleus...
  19. Tseng H, Arasteh A, Paranjpe A, Teruel A, Yang W, Behel A, et al. Increased lysis of stem cells but not their differentiated cells by natural killer cells; de-differentiation or reprogramming activates NK cells. PLoS ONE. 2010;5:e11590 pubmed publisher
    ..Therefore, patients with cancer may benefit from repeated allogeneic NK cell transplantation for specific elimination of cancer stem cells...
  20. Tashiro K, Pando M, Kanegae Y, Wamsley P, Inoue S, Verma I. Direct involvement of the ubiquitin-conjugating enzyme Ubc9/Hus5 in the degradation of IkappaBalpha. Proc Natl Acad Sci U S A. 1997;94:7862-7 pubmed
    The NF-kappaB/Rel proteins are sequestered in the cytoplasm in association with IkappaBalpha. In response to external signals, IkappaBalpha is phosphorylated, multi-ubiquitinated, and degraded by proteasomes, thereby releasing NF-kappaB/..
  21. Tergaonkar V, Bottero V, Ikawa M, Li Q, Verma I. IkappaB kinase-independent IkappaBalpha degradation pathway: functional NF-kappaB activity and implications for cancer therapy. Mol Cell Biol. 2003;23:8070-83 pubmed
    ..doxorubicin (DoxR), does not require the classical serine 32 and 36 phosphorylation or the PEST domain of IkappaBalpha. Degradation of IkappaBalpha is partially blocked by phosphatidylinositol 3-kinase inhibitor LY294002 and is ..
  22. Lee E, Boone D, Chai S, Libby S, Chien M, Lodolce J, et al. Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice. Science. 2000;289:2350-4 pubmed
    ..These cells are also more susceptible than control cells to undergo TNF-mediated PCD. Thus, A20 is critical for limiting inflammation by terminating TNF-induced NF-kappaB responses in vivo. ..
  23. Wyke S, Tisdale M. NF-kappaB mediates proteolysis-inducing factor induced protein degradation and expression of the ubiquitin-proteasome system in skeletal muscle. Br J Cancer. 2005;92:711-21 pubmed
    ..The ability of mutant I-kappaBalpha to inhibit PIF-induced protein degradation, as well as expression of the ubiquitin-proteasome pathway, confirms that both of these responses depend on initiation of transcription by NF-kappaB. ..
  24. Molotski N, Savion S, Gerchikov N, Fein A, Toder V, Torchinsky A. Teratogen-induced distortions in the classical NF-kappaB activation pathway: correlation with the ability of embryos to survive teratogenic stress. Toxicol Appl Pharmacol. 2008;229:197-205 pubmed publisher
    ..activity, expression of p65 and IKKbeta proteins, as well as NF-kappaB inhibitory proteins (IkappaBs) such as IkappaBalpha, IkappaBbeta, and IkappaBepsilon, and died within the next 24 h...
  25. Rupec R, Poujol D, Grosgeorge J, Carle G, Livolsi A, Peyron J, et al. Structural analysis, expression, and chromosomal localization of the mouse ikba gene. Immunogenetics. 1999;49:395-403 pubmed
    ..The cloning and determination of the structure are a prerequisite for the construction of vectors for conditional gene targeting experiments. ..
  26. Zhang Y, Liu J, Yao S, Li F, Xin L, Lai M, et al. Nuclear factor kappa B signaling initiates early differentiation of neural stem cells. Stem Cells. 2012;30:510-24 pubmed publisher
    ..Our data reveal a novel function of NF?B signaling in early neurogenesis and provide insight into the molecular mechanisms underlying neurodevelopmental disorders and neurodegenerative diseases. ..
  27. Szklarczyk K, Korostynski M, Golda S, Solecki W, Przewlocki R. Genotype-dependent consequences of traumatic stress in four inbred mouse strains. Genes Brain Behav. 2012;11:977-85 pubmed publisher
    ..C57BL/6J mice exhibited up-regulation in the expression of Tsc22d3, Nfkbia, Plat and Crhr1 genes in both brain regions...
  28. Mooster J, Le Bras S, Massaad M, Jabara H, Yoon J, Galand C, et al. Defective lymphoid organogenesis underlies the immune deficiency caused by a heterozygous S32I mutation in IκBα. J Exp Med. 2015;212:185-202 pubmed publisher
    ..Defective architectural cell function explains the immunodeficiency and poor outcome of HSCT in patients with IκBα deficiency and suggests that correction of this niche is critical for reconstituting their immune function. ..
  29. Iwasaki H, Takeuchi O, Teraguchi S, Matsushita K, Uehata T, Kuniyoshi K, et al. The I?B kinase complex regulates the stability of cytokine-encoding mRNA induced by TLR-IL-1R by controlling degradation of regnase-1. Nat Immunol. 2011;12:1167-75 pubmed publisher
    ..Our data demonstrate that the IKK complex phosphorylates not only I?B?, thereby activating transcription, but also regnase-1, thereby releasing a 'brake' on IL-6 mRNA expression. ..
  30. Grossman B, Shanley T, Odoms K, Dunsmore K, Denenberg A, Wong H. Temporal and mechanistic effects of heat shock on LPS-mediated degradation of IkappaBalpha in macrophages. Inflammation. 2002;26:129-37 pubmed
    Previous studies demonstrated important interactions between the heat shock response and the IkappaBalpha/NF-kappaB pathway when these two pathways are induced sequentially...
  31. Judge A, Koncarevic A, Hunter R, Liou H, Jackman R, Kandarian S. Role for IkappaBalpha, but not c-Rel, in skeletal muscle atrophy. Am J Physiol Cell Physiol. 2007;292:C372-82 pubmed
    ..Because endogenous inhibitory factor kappaBalpha (IkappaBalpha) was activated (i.e., decreased) at 3 and 7 days of muscle disuse (i.e...
  32. Lin J, Lin S, Chen W, Yen Y, Lai C, Tao M, et al. Dengue viral protease interaction with NF-?B inhibitor ?/? results in endothelial cell apoptosis and hemorrhage development. J Immunol. 2014;193:1258-67 pubmed publisher
    ..In this study, we show that DENV protease participates in the pathogenesis of dengue hemorrhage and discover I?B? and I?B? to be the new cellular targets that are cleaved by DENV protease. ..
  33. Sanchez Ponce D, Tapia M, Munoz A, Garrido J. New role of IKK alpha/beta phosphorylated I kappa B alpha in axon outgrowth and axon initial segment development. Mol Cell Neurosci. 2008;37:832-44 pubmed publisher
    ..These results demonstrate a new role for proteins of the NFkappaB pathway in the acquisition of neuronal polarity and its involvement in the development of the axon initial segment. ..
  34. Berg A, Lin Y, Lisanti M, Scherer P. Adipocyte differentiation induces dynamic changes in NF-kappaB expression and activity. Am J Physiol Endocrinol Metab. 2004;287:E1178-88 pubmed
    ..These effects are mediated by a secretory product of adipocytes that is unlikely to be IL-6 or TNF-alpha. ..
  35. Watanabe M, Dewan M, Taira M, Shoda M, Honda M, Sata T, et al. IkappaBalpha independent induction of NF-kappaB and its inhibition by DHMEQ in Hodgkin/Reed-Sternberg cells. Lab Invest. 2007;87:372-82 pubmed
    ..enhance NF-kappaB activation through IkappaB kinase activation in not only H-RS cell lines with wild-type IkappaBalpha, but also in those with IkappaBalpha mutations and lacking wild-type IkappaBalpha...
  36. Weih F, Carrasco D, Bravo R. Constitutive and inducible Rel/NF-kappa B activities in mouse thymus and spleen. Oncogene. 1994;9:3289-97 pubmed
    ..The Rel/NF-kappa B proteins and I kappa B alpha in thymus and spleen were also analysed by Western blotting and electrophoretic mobility shift assays...
  37. Wu S, Xia Y, Liu X, Sun J. Vitamin D receptor deletion leads to reduced level of IkappaBalpha protein through protein translation, protein-protein interaction, and post-translational modification. Int J Biochem Cell Biol. 2010;42:329-36 pubmed publisher
    ..However, it is unknown how vitamin D receptor regulates IkappaBalpha, the endogenous inhibitor of NF-kappaB...
  38. Yeh J, Hsu J, Hong Y, Wu J, Liang J, Wu B, et al. Eugenolol and glyceryl-isoeugenol suppress LPS-induced iNOS expression by down-regulating NF-kappaB AND AP-1 through inhibition of MAPKS and AKT/IkappaBalpha signaling pathways in macrophages. Int J Immunopathol Pharmacol. 2011;24:345-56 pubmed
    ..Thus, this study implies that eugenolol and glyceryl-isoeugenol may provide therapeutic benefits for inflammatory diseases. ..
  39. Nakayama K, Hatakeyama S, Maruyama S, Kikuchi A, Onoe K, Good R, et al. Impaired degradation of inhibitory subunit of NF-kappa B (I kappa B) and beta-catenin as a result of targeted disruption of the beta-TrCP1 gene. Proc Natl Acad Sci U S A. 2003;100:8752-7 pubmed
    ..We have now generated mice deficient in beta-TrCP1 and shown that the degradation of I kappa B alpha and I kappa B beta is reproducibly, but not completely, impaired in the cells of these animals...
  40. Shembade N, Pujari R, Harhaj N, Abbott D, Harhaj E. The kinase IKK? inhibits activation of the transcription factor NF-?B by phosphorylating the regulatory molecule TAX1BP1. Nat Immunol. 2011;12:834-43 pubmed publisher
    ..IKK? therefore serves a key role in the negative feedback of NF-?B canonical signaling by orchestrating assembly of the A20 ubiquitin-editing complex to limit inflammatory gene activation. ..
  41. Zhou J, Fan L, Li X, Calvet J, Li X. TNFα signaling regulates cystic epithelial cell proliferation through Akt/mTOR and ERK/MAPK/Cdk2 mediated Id2 signaling. PLoS ONE. 2015;10:e0131043 pubmed publisher
    ..As such, this study elucidates a novel mechanism for TNFα signaling in regulating cystic renal epithelial cell proliferation in ADPKD. ..
  42. Zmijewski J, Zhao X, Xu Z, Abraham E. Exposure to hydrogen peroxide diminishes NF-kappaB activation, IkappaB-alpha degradation, and proteasome activity in neutrophils. Am J Physiol Cell Physiol. 2007;293:C255-66 pubmed
    ..These results demonstrate that the effects of H(2)O(2) on NF-kappaB and proteasomal activity are cell population specific. ..
  43. Mulero M, Ferres Marco D, Islam A, Margalef P, Pecoraro M, Toll A, et al. Chromatin-bound I?B? regulates a subset of polycomb target genes in differentiation and cancer. Cancer Cell. 2013;24:151-66 pubmed publisher
    ..Accumulation of cytoplasmic I?B? was found in squamous cell carcinoma (SCC) associated with IKK activation and HOX upregulation. ..
  44. Okaya T, Lentsch A. Hepatic expression of S32A/S36A IkappaBalpha does not reduce postischemic liver injury. J Surg Res. 2005;124:244-9 pubmed, we sought to determine whether in vivo adenoviral transfection of a mutant inhibitor of kappaB-alpha (IkappaBalpha), which cannot be serine phosphorylated or degraded (IkappaBalphaSR), would inhibit NF-kappaB and ameliorate ..
  45. Schmidt Ullrich R, Tobin D, Lenhard D, Schneider P, Paus R, Scheidereit C. NF-kappaB transmits Eda A1/EdaR signalling to activate Shh and cyclin D1 expression, and controls post-initiation hair placode down growth. Development. 2006;133:1045-57 pubmed
    ..The strongly decreased number of hair follicles observed in c(IkappaBalphaDeltaN) mice compared with tabby mice, indicates that additional signals, such as TROY, must regulate NF-kappaB activity in specific hair follicle subtypes. ..
  46. Lian H, Yang L, Cole A, Sun L, Chiang A, Fowler S, et al. NFκB-activated astroglial release of complement C3 compromises neuronal morphology and function associated with Alzheimer's disease. Neuron. 2015;85:101-15 pubmed publisher
    ..Therefore, dysregulation of neuron-glia interaction through NFκB/C3/C3aR signaling may contribute to synaptic dysfunction in AD, and C3aR antagonists may be therapeutically beneficial. ..
  47. Hirano M, Osada S, Aoki T, Hirai S, Hosaka M, Inoue J, et al. MEK kinase is involved in tumor necrosis factor alpha-induced NF-kappaB activation and degradation of IkappaB-alpha. J Biol Chem. 1996;271:13234-8 pubmed
    ..These results suggest that MEK kinase is a signal mediator involved in TNFalpha-induced NF-kappaB activation and that the activation of NF-kappaB by MEK kinase is regulated through the degradation of IkappaB-alpha. ..
  48. Haudek S, Spencer E, Bryant D, White D, Maass D, Horton J, et al. Overexpression of cardiac I-kappaBalpha prevents endotoxin-induced myocardial dysfunction. Am J Physiol Heart Circ Physiol. 2001;280:H962-8 pubmed
    ..Inhibition of myocyte NF-kappaB activation by overexpression of myocyte I-kappaBalpha is sufficient to block cardiac TNF-alpha production and prevent cardiac dysfunction after LPS challenge...
  49. Werner S, Kearns J, Zadorozhnaya V, Lynch C, O Dea E, Boldin M, et al. Encoding NF-kappaB temporal control in response to TNF: distinct roles for the negative regulators IkappaBalpha and A20. Genes Dev. 2008;22:2093-101 pubmed publisher
    ..we identify two temporal amplification steps-one determined by the obligate negative feedback regulator IkappaBalpha-that define the duration of the first phase of NF-kappaB activity...
  50. Tazaki T, Miyazaki K, Hiyama E, Nakamoto T, Sakai R, Yamasaki N, et al. Functional analysis of Src homology 3-encoding exon (exon 2) of p130Cas in primary fibroblasts derived from exon 2-specific knockout mice. Genes Cells. 2008;13:145-57 pubmed publisher
    ..2 up-regulated expression of CXC Chemokine Receptor-4 and CC Chemokine Receptor-5, which may be regulated by IkappaBalpha phosphorylation...
  51. Chang N. The non-ankyrin C terminus of Ikappa Balpha physically interacts with p53 in vivo and dissociates in response to apoptotic stress, hypoxia, DNA damage, and transforming growth factor-beta 1-mediated growth suppression. J Biol Chem. 2002;277:10323-31 pubmed
    ..Exposure of Mv1Lu cells to TGF-beta1 rapidly resulted in down-regulation of cytosolic IkappaBalpha and hyaluronidase prevented this effect, suggesting a possible role of IkappaBalpha in the growth regulation...
  52. Guha M, Tang W, Sondheimer N, Avadhani N. Role of calcineurin, hnRNPA2 and Akt in mitochondrial respiratory stress-mediated transcription activation of nuclear gene targets. Biochim Biophys Acta. 2010;1797:1055-65 pubmed publisher
    ..We propose that mitochondrial stress plays an important role in tumor progression and emergence of invasive phenotypes. ..
  53. Lian H, Litvinchuk A, Chiang A, Aithmitti N, Jankowsky J, Zheng H. Astrocyte-Microglia Cross Talk through Complement Activation Modulates Amyloid Pathology in Mouse Models of Alzheimer's Disease. J Neurosci. 2016;36:577-89 pubmed publisher
    ..Our study provides support for targeting C3aR as a potential therapy for Alzheimer's disease. ..
  54. Tsuchiya Y, Asano T, Nakayama K, Kato T, Karin M, Kamata H. Nuclear IKKbeta is an adaptor protein for IkappaBalpha ubiquitination and degradation in UV-induced NF-kappaB activation. Mol Cell. 2010;39:570-82 pubmed publisher
    ..UV) irradiation does not lead to IKK activity, it activates NF-kappaB by an unknown mechanism through IkappaBalpha degradation without N-terminal phosphorylation...
  55. Bhattacharyya S, Pal P, Sil P. A 35 kD Phyllanthus niruri protein modulates iron mediated oxidative impairment to hepatocytes via the inhibition of ERKs, p38 MAPKs and activation of PI3k/Akt pathway. Food Chem Toxicol. 2013;56:119-30 pubmed publisher
    ..Moreover, this protein has strong free radical scavenging activity and thereby scavenged ROS extensively. Combining all, results suggest that simultaneous treatment with PNP might suppress the iron-induced cytotoxicity in hepatocytes...
  56. Ellinghaus U, Rupec R, Pabst O, Ignatius R, Forster R, Dorken B, et al. IkappaBalpha is required for marginal zone B cell lineage development. Eur J Immunol. 2008;38:2096-105 pubmed publisher
    ..Here, we show that mice with B cell-specific inactivation of the main NF-kappaB inhibitor IkappaBalpha have a marked decrease of MZB cells and their presumed precursors...
  57. Kizaki T, Izawa T, Sakurai T, Haga S, Taniguchi N, Tajiri H, et al. Beta2-adrenergic receptor regulates Toll-like receptor-4-induced nuclear factor-kappaB activation through beta-arrestin 2. Immunology. 2008;124:348-56 pubmed publisher
    ..The activation of nuclear factor-kappaB (NF-kappaB) and degradation of the inhibitor of NF-kappaB (IkappaBalpha) in response to LPS were markedly decreased in these cells...
  58. Neuhöfer P, Liang S, Einwächter H, Schwerdtfeger C, Wartmann T, Treiber M, et al. Deletion of I?B? activates RelA to reduce acute pancreatitis in mice through up-regulation of Spi2A. Gastroenterology. 2013;144:192-201 pubmed publisher
    ..Constitutive activation of RelA up-regulates Spi2A, which protects mice against the development of AP. ..
  59. Han W, Joo M, Everhart M, Christman J, Yull F, Blackwell T. Myeloid cells control termination of lung inflammation through the NF-kappaB pathway. Am J Physiol Lung Cell Mol Physiol. 2009;296:L320-7 pubmed publisher
    ..We generated bone marrow chimeras by fetal liver transplantation of cells deficient in IkappaBalpha or p50 into lethally irradiated NF-kappaB reporter transgenic mice...
  60. Baeza Raja B, Munoz Canoves P. p38 MAPK-induced nuclear factor-kappaB activity is required for skeletal muscle differentiation: role of interleukin-6. Mol Biol Cell. 2004;15:2013-26 pubmed
    ..Activation of p38 in C2C12 cells induced the activity of NF-kappaB, in a dual way: first, by reducing IkappaBalpha levels and inducing NF-kappaB-DNA binding activity and, second, by potentiating the transactivating activity of ..
  61. Claud E, Zhang X, Petrof E, Sun J. Developmentally regulated tumor necrosis factor-alpha induced nuclear factor-kappaB activation in intestinal epithelium. Am J Physiol Gastrointest Liver Physiol. 2007;292:G1411-9 pubmed
    ..Thus we demonstrate a potential mechanism for the heightened inflammatory response of immature intestinal epithelial cells. ..
  62. Elsawa S, Almada L, Ziesmer S, Novak A, Witzig T, Ansell S, et al. GLI2 transcription factor mediates cytokine cross-talk in the tumor microenvironment. J Biol Chem. 2011;286:21524-34 pubmed publisher
    ..Together, these results identify a novel signaling pathway mediating the stromal-cancer cell interactions, leading to increased Ig production by malignant cells. ..
  63. Ki S, Choi M, Lee C, Kim S. Galpha12 specifically regulates COX-2 induction by sphingosine 1-phosphate. Role for JNK-dependent ubiquitination and degradation of IkappaBalpha. J Biol Chem. 2007;282:1938-47 pubmed
    ..Galpha(12) deficiency did not affect S1P-mediated IkappaBalpha phosphorylation but abrogated IkappaBalpha ubiquitination and degradation...
  64. Inoue J, Kerr L, Kakizuka A, Verma I. I kappa B gamma, a 70 kd protein identical to the C-terminal half of p110 NF-kappa B: a new member of the I kappa B family. Cell. 1992;68:1109-20 pubmed
    ..The 70 kd protein, predominantly found in lymphoid cells, is a new member of the I kappa B family of proteins and is referred to as I kappa B gamma. ..
  65. O Connor S, Shumway S, Miyamoto S. Inhibition of IkappaBalpha nuclear export as an approach to abrogate nuclear factor-kappaB-dependent cancer cell survival. Mol Cancer Res. 2005;3:42-9 pubmed
    ..Here, we provide evidence that inhibition of IkappaBalpha nuclear export is a viable target to generally abrogate constitutive NF-kappaB activity in different cancer ..
  66. Gleason C, Ordureau A, Gourlay R, Arthur J, Cohen P. Polyubiquitin binding to optineurin is required for optimal activation of TANK-binding kinase 1 and production of interferon ?. J Biol Chem. 2011;286:35663-74 pubmed publisher
    ..In conclusion, our results suggest that OPTN binds to polyubiquitylated species formed in response to LPS and poly(I:C), enhancing the activation of TBK1 that is required for optimal phosphorylation of IRF3 and production of IFN?. ..
  67. Liu S, Chen J, Cai X, Wu J, Chen X, Wu Y, et al. MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling cascades. elife. 2013;2:e00785 pubmed publisher
    ..DOI: ..
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    ..The results indicate that following heat shock treatment, HuR translocates from the nucleus to the cytoplasm, forming stress granules and regulating the translation of I?B?? mRNA without affecting the half-life. ..
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    ..We further found that both isoforms are able to interact with CBP, suggesting a competition between Hoxa9 and Hoxa9T with this protein. ..
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    ..Moreover, PLCgamma2 was necessary for the full production of TNF-alpha and IL-6. These data indicate that the PLCgamma2 pathway plays an important role in bacterial ligands-induced activation of macrophages and dendritic cells. ..
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    ..of NF-kappaB is achieved by stimulus-induced ubiquitination and subsequent proteasome-mediated degradation of IkappaBalpha. Once released from the inhibitor, NF-kappaB/p65 enters the nucleus...