Gene Symbol: Ikbkb
Description: inhibitor of kappaB kinase beta
Alias: AI132552, IKK-2, IKK-beta, IKK2, IKK[b], IKKbeta, inhibitor of nuclear factor kappa-B kinase subunit beta, I-kappa-B kinase 2, I-kappa-B-kinase beta, IKK-B, NFKBIKB, inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta, nuclear factor NF-kappa-B inhibitor kinase beta
Species: mouse
Products:     Ikbkb

Top Publications

  1. Ren H, Schmalstieg A, Yuan D, Gaynor R. I-kappa B kinase beta is critical for B cell proliferation and antibody response. J Immunol. 2002;168:577-87 pubmed
    ..Stimulation of the NF-kappaB pathway leads to increases in I-kappaB kinase beta (IKKbeta) kinase activity to result in the enhanced phosphorylation and degradation of I-kappaB and the translocation of ..
  2. Broide D, Lawrence T, Doherty T, Cho J, Miller M, McElwain K, et al. Allergen-induced peribronchial fibrosis and mucus production mediated by IkappaB kinase beta-dependent genes in airway epithelium. Proc Natl Acad Sci U S A. 2005;102:17723-8 pubmed
    ..the contribution of epithelial cell NF-kappaB activation to the remodeling response, we generated CC10-Cre(tg)/Ikkbeta(delta/delta) mice in which NF-kappaB signaling through IkappaB kinase beta (IKKbeta) is selectively ablated in ..
  3. Kenneth N, Mudie S, Rocha S. IKK and NF-kappaB-mediated regulation of Claspin impacts on ATR checkpoint function. EMBO J. 2010;29:2966-78 pubmed publisher
    ..These results uncover a novel function for IKK and NF-kappaB modulating the DNA-damage checkpoint response, allowing the cell to integrate different signalling pathways with the DNA-damage response. ..
  4. Chen F, Lu Y, Castranova V, Li Z, Karin M. Loss of Ikkbeta promotes migration and proliferation of mouse embryo fibroblast cells. J Biol Chem. 2006;281:37142-9 pubmed
    ..Mice with genetic disruptions of the Ikkbeta or Ikkgamma gene loci die during embryogenesis because of severe hepatic apoptosis...
  5. Pasparakis M, Courtois G, Hafner M, Schmidt Supprian M, Nenci A, Toksoy A, et al. TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2. Nature. 2002;417:861-6 pubmed
    The I kappa B kinase (IKK), consisting of the IKK1 and IKK2 catalytic subunits and the NEMO (also known as IKK gamma) regulatory subunit, phosphorylates I kappa B proteins, targeting them for degradation and thus inducing activation of NF-..
  6. Takahashi H, Ogata H, Nishigaki R, Broide D, Karin M. Tobacco smoke promotes lung tumorigenesis by triggering IKKbeta- and JNK1-dependent inflammation. Cancer Cell. 2010;17:89-97 pubmed publisher
    ..Tumor promotion is due to induction of inflammation that results in enhanced pneumocyte proliferation and is abrogated by IKKbeta ablation in myeloid cells or inactivation of JNK1.
  7. Maeda S, Chang L, Li Z, Luo J, Leffert H, Karin M. IKKbeta is required for prevention of apoptosis mediated by cell-bound but not by circulating TNFalpha. Immunity. 2003;19:725-37 pubmed
    IkappaB kinase beta (IKKbeta) is required for NF-kappaB activation and suppression of TNFalpha-mediated liver apoptosis...
  8. Acharyya S, Villalta S, Bakkar N, Bupha Intr T, Janssen P, Carathers M, et al. Interplay of IKK/NF-kappaB signaling in macrophages and myofibers promotes muscle degeneration in Duchenne muscular dystrophy. J Clin Invest. 2007;117:889-901 pubmed
    ..In addition, conditional deletion of IKKbeta in mdx mice elucidated that NF-kappaB functions in activated macrophages to promote inflammation and muscle ..
  9. Wu C, Conze D, Li T, Srinivasula S, Ashwell J. Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-kappaB activation [corrected]. Nat Cell Biol. 2006;8:398-406 pubmed
    ..IKK has two catalytic subunits, IKKalpha and IKKbeta, and a regulatory subunit, IKKgamma or NEMO...

More Information


  1. Vacca A, Felli M, Palermo R, Di Mario G, Calce A, Di Giovine M, et al. Notch3 and pre-TCR interaction unveils distinct NF-kappaB pathways in T-cell development and leukemia. EMBO J. 2006;25:1000-8 pubmed
    ..A pre-TCR-dependent pathway preferentially activates NF-kappaB via IKKbeta/IKKalpha/NIK complex, resulting in p50/p65 heterodimer nuclear entry and recruitment onto promoters of Cyclin D1, ..
  2. Hsu L, Enzler T, Seita J, Timmer A, Lee C, Lai T, et al. IL-1?-driven neutrophilia preserves antibacterial defense in the absence of the kinase IKK?. Nat Immunol. 2011;12:144-50 pubmed publisher
  3. Senftleben U, Li Z, Baud V, Karin M. IKKbeta is essential for protecting T cells from TNFalpha-induced apoptosis. Immunity. 2001;14:217-30 pubmed
    Transcription factor NF-kappaB, whose activation depends on the IKKbeta catalytic subunit of the IkappaB kinase, was assigned with both anti- and proapoptotic functions in T lymphocytes...
  4. Shim J, Xiao C, Paschal A, Bailey S, Rao P, Hayden M, et al. TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo. Genes Dev. 2005;19:2668-81 pubmed
    ..Therefore, our studies suggests that TAK1 acts as an upstream activating kinase for IKKbeta and JNK, but not IKKalpha, revealing an unexpectedly specific role of TAK1 in inflammatory signaling pathways.
  5. Zaph C, Troy A, Taylor B, Berman Booty L, Guild K, Du Y, et al. Epithelial-cell-intrinsic IKK-beta expression regulates intestinal immune homeostasis. Nature. 2007;446:552-6 pubmed
    ..These results indicate that the balance of IKK-beta-dependent gene expression in the intestinal epithelium is crucial in intestinal immune homeostasis by promoting mucosal immunity and limiting chronic inflammation. ..
  6. Greten F, Eckmann L, Greten T, Park J, Li Z, Egan L, et al. IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell. 2004;118:285-96 pubmed
    ..Using a colitis-associated cancer model, we show that although deletion of IKKbeta in intestinal epithelial cells does not decrease inflammation, it leads to a dramatic decrease in tumor incidence ..
  7. Hu Y, Baud V, Delhase M, Zhang P, Deerinck T, Ellisman M, et al. Abnormal morphogenesis but intact IKK activation in mice lacking the IKKalpha subunit of IkappaB kinase. Science. 1999;284:316-20 pubmed
    The oligomeric IkappaB kinase (IKK) is composed of three polypeptides: IKKalpha and IKKbeta, the catalytic subunits, and IKKgamma, a regulatory subunit...
  8. Ghosh A, Roy A, Liu X, Kordower J, Mufson E, Hartley D, et al. Selective inhibition of NF-kappaB activation prevents dopaminergic neuronal loss in a mouse model of Parkinson's disease. Proc Natl Acad Sci U S A. 2007;104:18754-9 pubmed
    ..corresponding to the NF-kappaB essential modifier-binding domain (NBD) of IkappaB kinase alpha (IKKalpha) or IKKbeta to prevent nigrostriatal degeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of ..
  9. Mourkioti F, Kratsios P, Luedde T, Song Y, Delafontaine P, Adami R, et al. Targeted ablation of IKK2 improves skeletal muscle strength, maintains mass, and promotes regeneration. J Clin Invest. 2006;116:2945-54 pubmed
    ..NF-kappaB inhibition in mice, through targeted deletion of the activating kinase inhibitor of NF-kappaB kinase 2 (IKK2), shifted muscle fiber distribution and improved muscle force...
  10. Lattke M, Magnutzki A, Walther P, Wirth T, Baumann B. Nuclear factor ?B activation impairs ependymal ciliogenesis and links neuroinflammation to hydrocephalus formation. J Neurosci. 2012;32:11511-23 pubmed publisher
    ..Therefore, our study might open up new perspectives for the treatment of certain types of neonatal and childhood hydrocephalus associated with hemorrhages and infections. ..
  11. Röhl M, Pasparakis M, Baudler S, Baumgartl J, Gautam D, Huth M, et al. Conditional disruption of IkappaB kinase 2 fails to prevent obesity-induced insulin resistance. J Clin Invest. 2004;113:474-81 pubmed
    The inhibitor of NF-kappaB (IkappaB) kinases (IKK1[alpha] and IKK2[beta]), the catalytic subunits of the IKK complex, phosphorylate IkappaB proteins on serine residues, targeting them for degradation and thus activating the transcription ..
  12. Purkayastha S, Zhang G, Cai D. Uncoupling the mechanisms of obesity and hypertension by targeting hypothalamic IKK-? and NF-?B. Nat Med. 2011;17:883-7 pubmed publisher
    ..the proinflammatory protein nuclear factor ?B (NF-?B) and its upstream activator I?B kinase-? (IKK-?, encoded by Ikbkb) in the mediobasal hypothalamus rapidly elevated blood pressure in mice independently of obesity...
  13. He G, Yu G, Temkin V, Ogata H, Kuntzen C, Sakurai T, et al. Hepatocyte IKKbeta/NF-kappaB inhibits tumor promotion and progression by preventing oxidative stress-driven STAT3 activation. Cancer Cell. 2010;17:286-97 pubmed publisher
    The NF-kappaB activating kinase IKKbeta suppresses early chemically induced liver tumorigenesis by inhibiting hepatocyte death and compensatory proliferation...
  14. Tanaka M, Fuentes M, Yamaguchi K, Durnin M, Dalrymple S, Hardy K, et al. Embryonic lethality, liver degeneration, and impaired NF-kappa B activation in IKK-beta-deficient mice. Immunity. 1999;10:421-9 pubmed
    ..These results indicate that IKK-beta is crucial for liver development and regulation of NF-kappaB activity and that IKK-alpha can only partially compensate for the loss of IKK-beta. ..
  15. Zhang X, Zhang G, Zhang H, Karin M, Bai H, Cai D. Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity. Cell. 2008;135:61-73 pubmed publisher
    ..Here we show that a mediator of metabolic inflammation, IKKbeta/NF-kappaB, normally remains inactive although enriched in hypothalamic neurons...
  16. Greten F, Arkan M, Bollrath J, Hsu L, Goode J, Miething C, et al. NF-kappaB is a negative regulator of IL-1beta secretion as revealed by genetic and pharmacological inhibition of IKKbeta. Cell. 2007;130:918-31 pubmed
    b>IKKbeta-dependent NF-kappaB activation plays a key role in innate immunity and inflammation, and inhibition of IKKbeta has been considered as a likely anti-inflammatory therapy...
  17. Kanters E, Pasparakis M, Gijbels M, Vergouwe M, Partouns Hendriks I, Fijneman R, et al. Inhibition of NF-kappaB activation in macrophages increases atherosclerosis in LDL receptor-deficient mice. J Clin Invest. 2003;112:1176-85 pubmed
    ..atherogenesis, we used LDL receptor-deficient mice with a macrophage-restricted deletion of IkappaB kinase 2 (IKK2), which is essential for NF-kappaB activation by proinflammatory signals...
  18. Meng Q, Cai D. Defective hypothalamic autophagy directs the central pathogenesis of obesity via the IkappaB kinase beta (IKKbeta)/NF-kappaB pathway. J Biol Chem. 2011;286:32324-32 pubmed publisher
  19. Chang J, Liu F, Lee M, Wu B, Ting K, Zara J, et al. NF-?B inhibits osteogenic differentiation of mesenchymal stem cells by promoting ?-catenin degradation. Proc Natl Acad Sci U S A. 2013;110:9469-74 pubmed publisher
  20. Baumann B, Wagner M, Aleksic T, von Wichert G, Weber C, Adler G, et al. Constitutive IKK2 activation in acinar cells is sufficient to induce pancreatitis in vivo. J Clin Invest. 2007;117:1502-13 pubmed
    ..gene under the control of the rat elastase promoter were generated to mediate acinar cell-specific expression of IKK2 alleles...
  21. Shibata W, Takaishi S, Muthupalani S, Pritchard D, Whary M, Rogers A, et al. Conditional deletion of IkappaB-kinase-beta accelerates helicobacter-dependent gastric apoptosis, proliferation, and preneoplasia. Gastroenterology. 2010;138:1022-34.e1-10 pubmed publisher
    The nuclear factor kappaB (NF-kappaB)/IkappaB-kinase-beta (IKKbeta) pathway has been shown to represent a key link between inflammation and cancer, inducing pro-inflammatory cytokines in myeloid cells and anti-apoptotic pathways in ..
  22. Rius J, Guma M, Schachtrup C, Akassoglou K, Zinkernagel A, Nizet V, et al. NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Nature. 2008;453:807-11 pubmed publisher
    ..IKK-beta is also essential for HIF-1alpha accumulation in macrophages experiencing a bacterial infection. Hence, IKK-beta is an important physiological contributor to the hypoxic response, linking it to innate immunity and inflammation. ..
  23. Song L, Li J, Zhang D, Liu Z, Ye J, Zhan Q, et al. IKKbeta programs to turn on the GADD45alpha-MKK4-JNK apoptotic cascade specifically via p50 NF-kappaB in arsenite response. J Cell Biol. 2006;175:607-17 pubmed
    ..We provide a novel scenario of the proapoptotic role of IkappaB kinase beta (IKKbeta)-NF-kappaB, which can act as the activator of the JNK pathway through the induction of GADD45alpha for triggering ..
  24. Hou Y, Li F, Karin M, Ostrowski M. Analysis of the IKKbeta/NF-kappaB signaling pathway during embryonic angiogenesis. Dev Dyn. 2008;237:2926-35 pubmed publisher
    ..Conditional disruption of the Ikkbeta locus in endothelial cells using the well-characterized Tie2-Cre transgene resulted in embryonic lethality ..
  25. Oeckl P, Lattke M, Wirth T, Baumann B, Ferger B. Astrocyte-specific IKK2 activation in mice is sufficient to induce neuroinflammation but does not increase susceptibility to MPTP. Neurobiol Dis. 2012;48:481-7 pubmed publisher
    ..We used a transgenic mouse model expressing a constitutively active I?B-kinase-2 (IKK2-CA) in astrocytes under control of the human glial fibrillary acidic protein promotor (IKK2-mice) to investigate ..
  26. Stratis A, Pasparakis M, Markur D, Knaup R, Pofahl R, Metzger D, et al. Localized inflammatory skin disease following inducible ablation of I kappa B kinase 2 in murine epidermis. J Invest Dermatol. 2006;126:614-20 pubmed
    ..Using mice with conditionally targeted I kappa B kinase 2 (IKK2) alleles, we have previously shown that epidermal keratinocytes can play a dominant role in the ..
  27. Egan L, Eckmann L, Greten F, Chae S, Li Z, Myhre G, et al. IkappaB-kinasebeta-dependent NF-kappaB activation provides radioprotection to the intestinal epithelium. Proc Natl Acad Sci U S A. 2004;101:2452-7 pubmed
    ..Furthermore, bacterial lipopolysaccharide, which is normally a radioprotective agent, is radiosensitizing in IKKbeta-deficient intestinal epithelial cells...
  28. Schmeisser M, Baumann B, Johannsen S, Vindedal G, Jensen V, Hvalby Ø, et al. I?B kinase/nuclear factor ?B-dependent insulin-like growth factor 2 (Igf2) expression regulates synapse formation and spine maturation via Igf2 receptor signaling. J Neurosci. 2012;32:5688-703 pubmed publisher
    ..Using different models of conditional genetic inactivation of IKK2 function in mouse principal neurons, we show that IKK/NF-?B signaling is critically involved in synapse formation ..
  29. Luedde T, Beraza N, Kotsikoris V, Van Loo G, Nenci A, De Vos R, et al. Deletion of NEMO/IKKgamma in liver parenchymal cells causes steatohepatitis and hepatocellular carcinoma. Cancer Cell. 2007;11:119-32 pubmed
  30. Otero J, Dai S, Alhawagri M, Darwech I, Abu Amer Y. IKKbeta activation is sufficient for RANK-independent osteoclast differentiation and osteolysis. J Bone Miner Res. 2010;25:1282-94 pubmed publisher
    ..In this regard, introduction of constitutively activated IKKbeta (IKKbeta(SSEE)) but not wild-type IKKbeta into monocytes stimulates differentiation of bona fide osteoclasts in ..
  31. Luedde T, Assmus U, Wüstefeld T, Meyer zu Vilsendorf A, Roskams T, Schmidt Supprian M, et al. Deletion of IKK2 in hepatocytes does not sensitize these cells to TNF-induced apoptosis but protects from ischemia/reperfusion injury. J Clin Invest. 2005;115:849-59 pubmed
    The inhibitor of NF-kappaB (I-kappaB) kinase (IKK) complex consists of 3 subunits, IKK1, IKK2, and NF-kappaB essential modulator (NEMO), and is involved in the activation of NF-kappaB by various stimuli...
  32. Suzuki K, Verma I. Phosphorylation of SNAP-23 by IkappaB kinase 2 regulates mast cell degranulation. Cell. 2008;134:485-95 pubmed publisher
    ..Upon FcvarepsilonRI stimulation, IKK2 phosphorylates SNAP-23, the target membrane soluble N-ethylmaleimide-sensitive fusion factor attachment protein ..
  33. Malato Y, Sander L, Liedtke C, Al Masaoudi M, Tacke F, Trautwein C, et al. Hepatocyte-specific inhibitor-of-kappaB-kinase deletion triggers the innate immune response and promotes earlier cell proliferation during liver regeneration. Hepatology. 2008;47:2036-50 pubmed publisher
    ..by the IkappaB kinase (IKK) complex comprising inhibitor of kappaB kinase 1 (IKK1), inhibitor of kappaB kinase 2 (IKK2), and nuclear factor-B essential modifier (NEMO)...
  34. Zandi E, Karin M. Bridging the gap: composition, regulation, and physiological function of the IkappaB kinase complex. Mol Cell Biol. 1999;19:4547-51 pubmed
  35. Li Z, Omori S, Labuda T, Karin M, Rickert R. IKK beta is required for peripheral B cell survival and proliferation. J Immunol. 2003;170:4630-7 pubmed
    ..cells is regulated through the IkappaB kinase (IKK) complex, consisting of two catalytic subunits (IKKalpha and IKKbeta) and a regulatory subunit (IKKgamma)...
  36. 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. ..
  37. 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
    ..Here, we describe an adaptor function of nuclear IKKbeta in UV-induced IkappaBalpha degradation...
  38. Penzo M, Molteni R, Suda T, Samaniego S, Raucci A, Habiel D, et al. Inhibitor of NF-kappa B kinases alpha and beta are both essential for high mobility group box 1-mediated chemotaxis [corrected]. J Immunol. 2010;184:4497-509 pubmed publisher
    Inhibitor of NF-kappaB kinases beta (IKKbeta) and alpha (IKKalpha) activate distinct NF-kappaB signaling modules...
  39. Li Z, Chu W, Hu Y, Delhase M, Deerinck T, Ellisman M, et al. The IKKbeta subunit of IkappaB kinase (IKK) is essential for nuclear factor kappaB activation and prevention of apoptosis. J Exp Med. 1999;189:1839-45 pubmed
    The IkappaB kinase (IKK) complex is composed of three subunits, IKKalpha, IKKbeta, and IKKgamma (NEMO)...
  40. Tokunaga F, Sakata S, Saeki Y, Satomi Y, Kirisako T, Kamei K, et al. Involvement of linear polyubiquitylation of NEMO in NF-kappaB activation. Nat Cell Biol. 2009;11:123-32 pubmed publisher
    ..These results indicate that LUBAC is involved in the physiological regulation of the canonical NF-kappaB activation pathway through linear polyubiquitylation of NEMO. ..
  41. Hacker H, Redecke V, Blagoev B, Kratchmarova I, Hsu L, Wang G, et al. Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6. Nature. 2006;439:204-7 pubmed
  42. Jeong S, Pise Masison C, Radonovich M, Park H, Brady J. A novel NF-kappaB pathway involving IKKbeta and p65/RelA Ser-536 phosphorylation results in p53 Inhibition in the absence of NF-kappaB transcriptional activity. J Biol Chem. 2005;280:10326-32 pubmed
    ..We now present evidence that suggests that the upstream kinase IKKbeta plays an important role in Tax-induced p53 inhibition through phosphorylation of p65/RelA at Ser-536...
  43. Bockhart V, Constantin C, Häussler A, Wijnvoord N, Kanngiesser M, Myrczek T, et al. Inhibitor kappaB Kinase beta deficiency in primary nociceptive neurons increases TRP channel sensitivity. J Neurosci. 2009;29:12919-29 pubmed publisher
    ..We used mice with a Cre-loxP-mediated specific deletion of IKKbeta in sensory neurons of the dorsal root ganglion (SNS-IKKbeta(-/-)) to evaluate whether IKK plays a role in sensory ..
  44. Maier H, Schips T, Wietelmann A, Kruger M, Brunner C, Sauter M, et al. Cardiomyocyte-specific I?B kinase (IKK)/NF-?B activation induces reversible inflammatory cardiomyopathy and heart failure. Proc Natl Acad Sci U S A. 2012;109:11794-9 pubmed publisher
    ..generating an inducible transgenic mouse model with cardiomyocyte-specific expression of constitutively active IKK2. In adult animals, IKK2 activation led to inflammatory dilated cardiomyopathy and heart failure...
  45. Koch K, Maeda S, He G, Karin M, Leffert H. Targeted deletion of hepatocyte Ikkbeta confers growth advantages. Biochem Biophys Res Commun. 2009;380:349-54 pubmed publisher
    Mice lacking hepatocyte IKKbeta (Ikkbeta(Delta hep)) are defective in TNFalpha-activation of hepatocellular transcription factor NF-kappaB, and highly susceptible to hepatotoxicity...
  46. Nakano H, Shindo M, Sakon S, Nishinaka S, Mihara M, Yagita H, et al. Differential regulation of IkappaB kinase alpha and beta by two upstream kinases, NF-kappaB-inducing kinase and mitogen-activated protein kinase/ERK kinase kinase-1. Proc Natl Acad Sci U S A. 1998;95:3537-42 pubmed
    ..Recently, two closely related kinases, designated IKKalpha and IKKbeta, have been identified to be the components of the IKK complex that phosphorylate critical serine residues of ..
  47. Luedde T, Heinrichsdorff J, De Lorenzi R, De Vos R, Roskams T, Pasparakis M. IKK1 and IKK2 cooperate to maintain bile duct integrity in the liver. Proc Natl Acad Sci U S A. 2008;105:9733-8 pubmed publisher
    ..Here, we show that the two IkappaB kinases, IKK1/IKKalpha and IKK2/IKKbeta, display distinct collaborative and specific functions that are essential to protect the liver from cytokine ..
  48. Verma I, Stevenson J, Schwarz E, Van Antwerp D, Miyamoto S. Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation. Genes Dev. 1995;9:2723-35 pubmed
  49. Maniati E, Bossard M, Cook N, Candido J, Emami Shahri N, Nedospasov S, et al. Crosstalk between the canonical NF-?B and Notch signaling pathways inhibits Ppar? expression and promotes pancreatic cancer progression in mice. J Clin Invest. 2011;121:4685-99 pubmed publisher
    ..Here, we show that inhibitor of ?B kinase 2 (Ikk2), a component of the canonical NF-?B signaling pathway, synergizes with basal Notch signaling to upregulate ..
  50. Dai S, Hirayama T, Abbas S, Abu Amer Y. The IkappaB kinase (IKK) inhibitor, NEMO-binding domain peptide, blocks osteoclastogenesis and bone erosion in inflammatory arthritis. J Biol Chem. 2004;279:37219-22 pubmed
    ..The IKK complex contains primarily IKKalpha, IKKbeta, and the regulatory kinase IKKgamma, also known as NEMO...
  51. Mankan A, Canli O, Schwitalla S, Ziegler P, Tschopp J, Korn T, et al. TNF-alpha-dependent loss of IKKbeta-deficient myeloid progenitors triggers a cytokine loop culminating in granulocytosis. Proc Natl Acad Sci U S A. 2011;108:6567-72 pubmed publisher
    ..These results unravel so far unanticipated direct and indirect functions for IKK? in myeloid progenitor survival and maintenance of innate and Th17 immunity and raise concerns about long-term IKK? inhibition in IL-17-mediated diseases. ..
  52. Arkan M, Hevener A, Greten F, Maeda S, Li Z, Long J, et al. IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med. 2005;11:191-8 pubmed
    ..IkappaB kinase beta (IKK-beta, encoded by Ikbkb) is a central coordinator of inflammatory responses through activation of NF-kappaB...
  53. Takeda K, Takeuchi O, Tsujimura T, Itami S, Adachi O, Kawai T, et al. Limb and skin abnormalities in mice lacking IKKalpha. Science. 1999;284:313-6 pubmed
  54. Fong C, Bebien M, Didierlaurent A, Nebauer R, Hussell T, Broide D, et al. An antiinflammatory role for IKKbeta through the inhibition of "classical" macrophage activation. J Exp Med. 2008;205:1269-76 pubmed publisher
    ..Using Cre/lox-mediated gene targeting of IKKbeta, we have uncovered a tissue-specific role for IKKbeta during infection with group B streptococcus...
  55. Rasoulpour R, Boekelheide K. NF-kappaB activation elicited by ionizing radiation is proapoptotic in testis. Biol Reprod. 2007;76:279-85 pubmed
    ..Inhibiting activity of one of the catalytic subunits of the IKK complex, IKKbeta (also known as IKBKB and IKK2) severely inhibits NF-kappaB nuclear translocation in response to most stimuli, ..
  56. Ruocco M, Maeda S, Park J, Lawrence T, Hsu L, Cao Y, et al. 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. J Exp Med. 2005;201:1677-87 pubmed
    ..of the two catalytic subunits of the IkappaB kinase (IKK) complex that mediate NF-kappaB activation, IKKalpha and IKKbeta, in osteoclast formation and inflammation-induced bone loss...
  57. Hu M, Lee D, Xia W, Golfman L, Ou Yang F, Yang J, et al. IkappaB kinase promotes tumorigenesis through inhibition of forkhead FOXO3a. Cell. 2004;117:225-37 pubmed
    ..Cytoplasmic FOXO3a correlates with expression of IKKbeta or Akt-p in many tumors and associates with poor survival in breast cancer...
  58. Cai D, Yuan M, Frantz D, Melendez P, Hansen L, Lee J, et al. Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med. 2005;11:183-90 pubmed
    ..This causes insulin resistance both locally in liver and systemically. ..
  59. Zhang G, Li J, Purkayastha S, Tang Y, Zhang H, Yin Y, et al. Hypothalamic programming of systemic ageing involving IKK-?, NF-?B and GnRH. Nature. 2013;497:211-6 pubmed publisher
  60. Li Q, Estepa G, Memet S, Israel A, Verma I. Complete lack of NF-kappaB activity in IKK1 and IKK2 double-deficient mice: additional defect in neurulation. Genes Dev. 2000;14:1729-33 pubmed
    NF-kappaB activity is induced by cytokines, stress, and pathogens. IKK1 and IKK2 are critical IkappaB kinases in NF-kappaB activation. In this study mice lacking IKK1 and IKK2 died at E12...
  61. Schmid J, Birbach A. IkappaB kinase beta (IKKbeta/IKK2/IKBKB)--a key molecule in signaling to the transcription factor NF-kappaB. Cytokine Growth Factor Rev. 2008;19:157-65 pubmed publisher
    b>IKKbeta/IKBKB (IkappaB kinase beta), also designated as IKK2, was named after its function of phosphorylating IkappaB molecules, the inhibitors of NF-kappaB transcription factors...
  62. Tang G, Minemoto Y, Dibling B, Purcell N, Li Z, Karin M, et al. Inhibition of JNK activation through NF-kappaB target genes. Nature. 2001;414:313-7 pubmed
    ..We investigated this using murine embryonic fibroblasts that are deficient in either the IKKbeta catalytic subunit of the IKK complex or the RelA/p65 subunit of NF-kappaB...
  63. Hikoso S, Yamaguchi O, Nakano Y, Takeda T, Omiya S, Mizote I, et al. The I{kappa}B kinase {beta}/nuclear factor {kappa}B signaling pathway protects the heart from hemodynamic stress mediated by the regulation of manganese superoxide dismutase expression. Circ Res. 2009;105:70-9 pubmed publisher
    ..Then, we investigated the role of the activation using cardiac-specific IKKbeta-deficient mice (CKO)...
  64. Otero J, Dai S, Foglia D, Alhawagri M, Vacher J, Pasparakis M, et al. Defective osteoclastogenesis by IKKbeta-null precursors is a result of receptor activator of NF-kappaB ligand (RANKL)-induced JNK-dependent apoptosis and impaired differentiation. J Biol Chem. 2008;283:24546-53 pubmed publisher
    ..the master osteoclastogenic cytokine, induces apoptosis of osteoclast precursors (OCPs) in the absence of IKKbeta/NF-kappaB competency...
  65. Schmidt Supprian M, Courtois G, Tian J, Coyle A, Israel A, Rajewsky K, et al. Mature T cells depend on signaling through the IKK complex. Immunity. 2003;19:377-89 pubmed
    ..The IkappaB kinase (IKK) complex, consisting of two kinases, IKK1/alpha and IKK2/beta, and the NEMO/IKKgamma regulatory subunit, mediates NF-kappaB activation by most known stimuli...
  66. Van Loo G, De Lorenzi R, Schmidt H, Huth M, Mildner A, Schmidt Supprian M, et al. Inhibition of transcription factor NF-kappaB in the central nervous system ameliorates autoimmune encephalomyelitis in mice. Nat Immunol. 2006;7:954-61 pubmed
    ..Here we show that CNS-restricted ablation of 'upstream' NF-kappaB activators NEMO or IKK2 but not IKK1 ameliorated disease pathology in a mouse model of multiple sclerosis, suggesting that 'canonical' NF-..
  67. Li Q, Van Antwerp D, Mercurio F, Lee K, Verma I. Severe liver degeneration in mice lacking the IkappaB kinase 2 gene. Science. 1999;284:321-5 pubmed
    ..the transcription nuclear factor kappa B (NF-kappaB) and requires two IkappaB kinases, IKK1 (IKKalpha) and IKK2 (IKKbeta)...
  68. Park J, Greten F, Li Z, Karin M. Macrophage apoptosis by anthrax lethal factor through p38 MAP kinase inhibition. Science. 2002;297:2048-51 pubmed
    ..This dismantling of the p38 MAPK module represents a strategy used by B. anthracis to paralyze host innate immunity. ..
  69. Herrmann O, Baumann B, De Lorenzi R, Muhammad S, Zhang W, Kleesiek J, et al. IKK mediates ischemia-induced neuronal death. Nat Med. 2005;11:1322-9 pubmed
    ..To investigate the function of IKK in brain ischemia we generated mice that contain a targeted deletion of Ikbkb (which encodes IKK2) in mouse neurons and mice that express a dominant inhibitor of IKK in neurons...
  70. Pauls E, Shpiro N, Peggie M, Young E, Sorcek R, Tan L, et al. Essential role for IKK? in production of type 1 interferons by plasmacytoid dendritic cells. J Biol Chem. 2012;287:19216-28 pubmed publisher
  71. Chen L, Egan L, Li Z, Greten F, Kagnoff M, Karin M. The two faces of IKK and NF-kappaB inhibition: prevention of systemic inflammation but increased local injury following intestinal ischemia-reperfusion. Nat Med. 2003;9:575-81 pubmed
    ..These results show the dual function of the NF-kappaB system, which is responsible for both tissue protection and systemic inflammation, and underscore the caution that should be exerted in using NF-kappaB and IKK inhibitors. ..
  72. Matsuzawa A, Tseng P, Vallabhapurapu S, Luo J, Zhang W, Wang H, et al. Essential cytoplasmic translocation of a cytokine receptor-assembled signaling complex. Science. 2008;321:663-8 pubmed publisher
    ..This two-stage signaling mechanism may apply to other innate immune receptors, accounting for spatial and temporal separation of MAPK and IKK signaling. ..