IKKbeta

Summary

Gene Symbol: IKKbeta
Description: inhibitor of nuclear factor kappa B kinase subunit beta
Alias: IKK-beta, IKK2, IKKB, IMD15, NFKBIKB, inhibitor of nuclear factor kappa-B kinase subunit beta, I-kappa-B kinase 2, I-kappa-B-kinase beta, IKK-B, inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta, nuclear factor NF-kappa-B inhibitor kinase beta
Species: human
Products:     IKKbeta

Top Publications

  1. 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...
  2. Ninomiya Tsuji J, Kajino T, Ono K, Ohtomo T, Matsumoto M, Shiina M, et al. A resorcylic acid lactone, 5Z-7-oxozeaenol, prevents inflammation by inhibiting the catalytic activity of TAK1 MAPK kinase kinase. J Biol Chem. 2003;278:18485-90 pubmed
    ..Furthermore, in vivo 5Z-7-oxozeaenol was able to inhibit picryl chloride-induced ear swelling. Thus, 5Z-7-oxozeaenol blocks proinflammatory signaling by selectively inhibiting TAK1 MAPKKK. ..
  3. May M, Larsen S, Shim J, Madge L, Ghosh S. A novel ubiquitin-like domain in IkappaB kinase beta is required for functional activity of the kinase. J Biol Chem. 2004;279:45528-39 pubmed
    Activation of NF-kappaB requires two highly related kinases named IKKalpha and IKKbeta that share identity in the nature and positioning of their structural domains...
  4. Arch R, Gedrich R, Thompson C. Tumor necrosis factor receptor-associated factors (TRAFs)--a family of adapter proteins that regulates life and death. Genes Dev. 1998;12:2821-30 pubmed
  5. Xia Y, Padre R, de Mendoza T, Bottero V, Tergaonkar V, Verma I. Phosphorylation of p53 by IkappaB kinase 2 promotes its degradation by beta-TrCP. Proc Natl Acad Sci U S A. 2009;106:2629-34 pubmed publisher
    ..In this study, we show that IkappaB kinase 2 (IKK2/IKKbeta), which is critical for NF-kappaB activation, also phosphorylates p53...
  6. Ducut Sigala J, Bottero V, Young D, Shevchenko A, Mercurio F, Verma I. Activation of transcription factor NF-kappaB requires ELKS, an IkappaB kinase regulatory subunit. Science. 2004;304:1963-7 pubmed
    ..These cells were also not protected from apoptosis in response to cytokines. ELKS likely functions by recruiting IkappaBalpha to the IKK complex and thus serves a regulatory function for IKK activation. ..
  7. Palkowitsch L, Leidner J, Ghosh S, Marienfeld R. Phosphorylation of serine 68 in the IkappaB kinase (IKK)-binding domain of NEMO interferes with the structure of the IKK complex and tumor necrosis factor-alpha-induced NF-kappaB activity. J Biol Chem. 2008;283:76-86 pubmed
    ..Besides the two kinases IKKalpha and IKKbeta, the IKK complex contains NEMO/IKKgamma, an additional subunit with regulatory and adaptor functions...
  8. Rothwarf D, Zandi E, Natoli G, Karin M. IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex. Nature. 1998;395:297-300 pubmed
    ..IKK-gamma interacts preferentially with IKK-beta and is required for the activation of the IKK complex. An IKK-gamma carboxy-terminal truncation mutant that still binds IKK-beta blocks the activation of IKK and NF-kappaB. ..
  9. Sun L, Deng L, Ea C, Xia Z, Chen Z. The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. Mol Cell. 2004;14:289-301 pubmed
    ..These results reveal an oligomerization --> ubiquitination --> phosphorylation cascade that culminates in NF-kappaB activation in T lymphocytes. ..

More Information

Publications83

  1. Mercurio F, Zhu H, Murray B, Shevchenko A, Bennett B, Li J, et al. IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF-kappaB activation. Science. 1997;278:860-6 pubmed
    ..Mutant versions of IKK-2 had pronounced effects on RelA nuclear translocation and NF-kappaB-dependent reporter activity, consistent with a critical role for the IKK kinases in the NF-kappaB signaling pathway. ..
  2. Chen G, Cao P, Goeddel D. TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90. Mol Cell. 2002;9:401-10 pubmed
    The IKK complex, containing two catalytic subunits IKKalpha and IKKbeta and a regulatory subunit NEMO, plays central roles in signal-dependent activation of NF-kappaB...
  3. Chen R, Alvero A, Silasi D, Kelly M, Fest S, Visintin I, et al. Regulation of IKKbeta by miR-199a affects NF-kappaB activity in ovarian cancer cells. Oncogene. 2008;27:4712-23 pubmed publisher
    ..Cancer progression is an abnormal form of tissue repair characterized by chronic inflammation. IkappaB kinase-beta (IKKbeta) required for nuclear factor-kappaB (NF-kappaB) activation plays a critical role in this process...
  4. Zandi E, Rothwarf D, Delhase M, Hayakawa M, Karin M. The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation. Cell. 1997;91:243-52 pubmed
    ..We now describe the molecular cloning and characterization of IKKbeta, a second subunit of the IKK complex...
  5. Tokunaga F, Nakagawa T, Nakahara M, Saeki Y, Taniguchi M, Sakata S, et al. SHARPIN is a component of the NF-?B-activating linear ubiquitin chain assembly complex. Nature. 2011;471:633-6 pubmed publisher
  6. Devin A, Lin Y, Yamaoka S, Li Z, Karin M, Liu Zg -. The alpha and beta subunits of IkappaB kinase (IKK) mediate TRAF2-dependent IKK recruitment to tumor necrosis factor (TNF) receptor 1 in response to TNF. Mol Cell Biol. 2001;21:3986-94 pubmed
    ..IKK is a complex composed of three subunits: IKKalpha, IKKbeta, and IKKgamma (also called NEMO)...
  7. Delhase M, Hayakawa M, Chen Y, Karin M. Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation. Science. 1999;284:309-13 pubmed
    ..IKK is composed of three subunits-IKKalpha and IKKbeta, which are highly similar protein kinases, and IKKgamma, a regulatory subunit...
  8. Cummins E, Berra E, Comerford K, Ginouves A, Fitzgerald K, Seeballuck F, et al. Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving insight into hypoxia-induced NFkappaB activity. Proc Natl Acad Sci U S A. 2006;103:18154-9 pubmed
    ..we demonstrate that hypoxia activates NFkappaB through a pathway involving activation of IkappaB kinase-beta (IKKbeta) leading to phosphorylation-dependent degradation of IkappaBalpha and liberation of NFkappaB...
  9. Strnad J, McDonnell P, Riexinger D, Mapelli C, Cheng L, Gray H, et al. NEMO binding domain of IKK-2 encompasses amino acids 735-745. J Mol Recognit. 2006;19:227-33 pubmed
    ..These longer NBD-containing peptides may be required to give the NBD an appropriate conformation for recognition by NEMO and/or to provide for additional interactions with NEMO. ..
  10. Sakurai H, Suzuki S, Kawasaki N, Nakano H, Okazaki T, Chino A, et al. Tumor necrosis factor-alpha-induced IKK phosphorylation of NF-kappaB p65 on serine 536 is mediated through the TRAF2, TRAF5, and TAK1 signaling pathway. J Biol Chem. 2003;278:36916-23 pubmed
    ..In addition, overexpression of TGF-beta-activated kinase 1 (TAK1), IKKalpha and IKKbeta stimulated the phosphorylation, and their dominant negative mutants blocked the TNF-alpha-induced phosphorylation...
  11. DiDonato J, Hayakawa M, Rothwarf D, Zandi E, Karin M. A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB. Nature. 1997;388:548-54 pubmed
    ..A component of IKK was molecularly cloned and identified as a serine kinase. IKK turns out to be the long-sought-after protein kinase that mediates the critical regulatory step in NF-kappaB activation. ..
  12. Hai T, Yeung M, Wood T, Wei Y, Yamaoka S, Gatalica Z, et al. An alternative splice product of IkappaB kinase (IKKgamma), IKKgamma-delta, differentially mediates cytokine and human T-cell leukemia virus type 1 tax-induced NF-kappaB activation. J Virol. 2006;80:4227-41 pubmed
    ..The core IKK consists of two catalytic serine kinases, IKKalpha and IKKbeta, and a noncatalytic subunit, IKKgamma...
  13. Wu X, Sun S. Retroviral oncoprotein Tax deregulates NF-kappaB by activating Tak1 and mediating the physical association of Tak1-IKK. EMBO Rep. 2007;8:510-5 pubmed
    ..These findings show a pathological mechanism of IKK activation by Tax and provide an example for how IKK is persistently activated in cancer cells. ..
  14. Chan C, Yau T, Jin D, Wong C, Fan S, Ng I. Evaluation of nuclear factor-kappaB, urokinase-type plasminogen activator, and HBx and their clinicopathological significance in hepatocellular carcinoma. Clin Cancer Res. 2004;10:4140-9 pubmed
    ..activation was induced by HBx transfection in HepG2 cells through inhibitor of nuclear factor-kappaB kinase beta (IKKbeta). HBx also up-regulated uPA and enhanced cell invasion synergistically with IKKbeta...
  15. 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. ..
  16. Polley S, Huang D, Hauenstein A, Fusco A, Zhong X, Vu D, et al. A structural basis for I?B kinase 2 activation via oligomerization-dependent trans auto-phosphorylation. PLoS Biol. 2013;11:e1001581 pubmed publisher
    ..Here we report a 4 Å x-ray crystal structure of human IKK2 (hIKK2) in its catalytically active conformation...
  17. 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...
  18. Huang W, Chen J, Chen C. c-Src-dependent tyrosine phosphorylation of IKKbeta is involved in tumor necrosis factor-alpha-induced intercellular adhesion molecule-1 expression. J Biol Chem. 2003;278:9944-52 pubmed
    ..plasmids induced ICAM-1 promoter activity, this effect being inhibited by the dominant-negative c-Src (KM) or IKKbeta (KM) mutant but not by the nuclear factor-kappaB-inducing kinase (NIK) (KA) mutant...
  19. Ea C, Deng L, Xia Z, Pineda G, Chen Z. Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO. Mol Cell. 2006;22:245-57 pubmed
    ..These results reveal the biochemical mechanism underlying the essential signaling function of NEMO and provide direct evidence that signal-induced site-specific ubiquitination of RIP1 is required for IKK activation. ..
  20. Lamberti C, Lin K, Yamamoto Y, Verma U, Verma I, Byers S, et al. Regulation of beta-catenin function by the IkappaB kinases. J Biol Chem. 2001;276:42276-86 pubmed
    ..Two kinases, IKKalpha and IKKbeta, are critical activators of the NF-kappaB pathway...
  21. Deng L, Wang C, Spencer E, Yang L, Braun A, You J, et al. Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell. 2000;103:351-61 pubmed
    ..These results unveil a new regulatory function for ubiquitin, in which IKK is activated through the assembly of K63-linked polyubiquitin chains. ..
  22. Chen Z, Parent L, Maniatis T. Site-specific phosphorylation of IkappaBalpha by a novel ubiquitination-dependent protein kinase activity. Cell. 1996;84:853-62 pubmed
    ..We also show that a ubiquitination event in the kinase complex is a prerequisite for specific phosphorylation of IkappaBalpha. Thus, ubiquitination serves a novel regulatory function that does not involve proteolysis. ..
  23. Khan K, Abbas W, Varin A, Kumar A, Di Martino V, Dichamp I, et al. HIV-1 Nef interacts with HCV Core, recruits TRAF2, TRAF5 and TRAF6, and stimulates HIV-1 replication in macrophages. J Innate Immun. 2013;5:639-56 pubmed publisher
  24. Karim Z, Zhang J, Banerjee M, Chicka M, Al Hawas R, Hamilton T, et al. I?B kinase phosphorylation of SNAP-23 controls platelet secretion. Blood. 2013;121:4567-74 pubmed publisher
    ..In vivo studies with IKK inhibitors or platelet-specific IKK-? knockout mice showed that blocking IKK-? activity significantly prolonged tail bleeding times, suggesting that currently available IKK inhibitors may affect hemostasis. ..
  25. Song L, Huang Q, Chen K, Liu L, Lin C, Dai T, et al. miR-218 inhibits the invasive ability of glioma cells by direct downregulation of IKK-?. Biochem Biophys Res Commun. 2010;402:135-40 pubmed publisher
    ..Taken together, our results suggest that miR-218 plays an important role in preventing the invasiveness of glioma cells, and our results present a novel mechanism of miRNA-mediated direct suppression of IKK-?/NF-?B pathway in gliomas. ..
  26. May M, D Acquisto F, Madge L, Glockner J, Pober J, Ghosh S. Selective inhibition of NF-kappaB activation by a peptide that blocks the interaction of NEMO with the IkappaB kinase complex. Science. 2000;289:1550-4 pubmed
    ..the activity of an inhibitor of kappaB (IkappaB)-kinase (IKK) complex containing two kinases (IKKalpha and IKKbeta) and the regulatory protein NEMO (NF-kappaB essential modifier)...
  27. Tegethoff S, Behlke J, Scheidereit C. Tetrameric oligomerization of IkappaB kinase gamma (IKKgamma) is obligatory for IKK complex activity and NF-kappaB activation. Mol Cell Biol. 2003;23:2029-41 pubmed
    ..Its catalytic subunits, IKKalpha and IKKbeta, require association with the regulatory IKKgamma (NEMO) component to gain full basal and inducible kinase ..
  28. Yang J, Lin Y, Guo Z, Cheng J, Huang J, Deng L, et al. The essential role of MEKK3 in TNF-induced NF-kappaB activation. Nat Immunol. 2001;2:620-4 pubmed
    ..We have also shown that MEKK3 interacts with RIP and directly phosphorylates IKK. The kinase activity of MEKK3 is pivotal to its function and, therefore, MEKK3 links RIP and IKK in TNF-induced NF-kappaB activation. ..
  29. Wang C, Deng L, Hong M, Akkaraju G, Inoue J, Chen Z. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature. 2001;412:346-51 pubmed
    ..We also provide evidence that TRAF6 is conjugated by the K63 polyubiquitin chains. These results indicate that ubiquitination has an important regulatory role in stress response pathways, including those of IKK and JNK. ..
  30. Liu L, Eby M, Rathore N, Sinha S, Kumar A, Chaudhary P. The human herpes virus 8-encoded viral FLICE inhibitory protein physically associates with and persistently activates the Ikappa B kinase complex. J Biol Chem. 2002;277:13745-51 pubmed
    ..gets recruited to a approximately 700-kDa IkappaB kinase (IKK) complex and physically associates with IKKalpha, IKKbeta, NEMO/IKKgamma, and RIP...
  31. Khoshnan A, Ko J, Tescu S, Brundin P, Patterson P. IKKalpha and IKKbeta regulation of DNA damage-induced cleavage of huntingtin. PLoS ONE. 2009;4:e5768 pubmed publisher
    ..This event requires IKKbeta and is suppressed by IKKalpha...
  32. Jiang R, Xia Y, Li J, Deng L, Zhao L, Shi J, et al. High expression levels of IKKalpha and IKKbeta are necessary for the malignant properties of liver cancer. Int J Cancer. 2010;126:1263-74 pubmed publisher
    ..we analyzed the expression of mRNAs encoding components and targets of NF-kappaB signaling including IKKalpha, IKKbeta, RANK, RANKL, OPG, CyclinD3, mammary serine protease inhibitor (Maspin), CyclinD1, c-FLIP, Bcl-xl, Stat3, Cip1 ..
  33. Haas T, Emmerich C, Gerlach B, Schmukle A, Cordier S, Rieser E, et al. Recruitment of the linear ubiquitin chain assembly complex stabilizes the TNF-R1 signaling complex and is required for TNF-mediated gene induction. Mol Cell. 2009;36:831-44 pubmed publisher
    ..Finally, we demonstrate that sustained stability of the TNF-RSC requires LUBAC's enzymatic activity, thereby adding a third form of ubiquitin linkage to the triggering of TNF signaling by the TNF-RSC. ..
  34. Schneider F, Neugebauer J, Griese J, Liefold N, Kutz H, Briseño C, et al. The viral oncoprotein LMP1 exploits TRADD for signaling by masking its apoptotic activity. PLoS Biol. 2008;6:e8 pubmed publisher
    ..is a critical signaling mediator of LMP1 that is required for LMP1 to recruit and activate I-kappaB kinase beta (IKKbeta). However, in contrast to TNFR1, LMP1-induced TRADD signaling does not induce apoptosis...
  35. Pannicke U, Baumann B, Fuchs S, Henneke P, Rensing Ehl A, Rizzi M, et al. Deficiency of innate and acquired immunity caused by an IKBKB mutation. N Engl J Med. 2013;369:2504-14 pubmed publisher
    ..All patients carried a homozygous duplication--c.1292dupG in exon 13 of IKBKB, which encodes I?B kinase 2 (IKK2, also known as IKK?)--leading to loss of expression of IKK2, a component of the IKK-nuclear factor ?B (NF-?B) ..
  36. Hacker H, Karin M. Regulation and function of IKK and IKK-related kinases. Sci STKE. 2006;2006:re13 pubmed
    ..Two protein kinases with a high degree of sequence similarity, IKKalpha and IKKbeta, mediate phosphorylation of IkappaB proteins and represent a convergence point for most signal transduction ..
  37. Emmerich C, Ordureau A, Strickson S, Arthur J, Pedrioli P, Komander D, et al. Activation of the canonical IKK complex by K63/M1-linked hybrid ubiquitin chains. Proc Natl Acad Sci U S A. 2013;110:15247-52 pubmed publisher
    ..Our study may help to resolve the debate about the relative importance of K63-pUb and M1-pUb chains in activating the canonical IKK complex. ..
  38. Rushe M, Silvian L, Bixler S, Chen L, Cheung A, Bowes S, et al. Structure of a NEMO/IKK-associating domain reveals architecture of the interaction site. Structure. 2008;16:798-808 pubmed publisher
    ..We demonstrate that the NEMO core domain is a dimer that binds two IKK fragments and identify energetic hot spots that can be exploited to inhibit IKK complex formation with a therapeutic agent. ..
  39. 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...
  40. Salmeron A, Janzen J, Soneji Y, Bump N, Kamens J, Allen H, et al. Direct phosphorylation of NF-kappaB1 p105 by the IkappaB kinase complex on serine 927 is essential for signal-induced p105 proteolysis. J Biol Chem. 2001;276:22215-22 pubmed
    ..individually changed to alanine established that only serine 927 is essential for p105 proteolysis triggered by IKK2 overexpression. This residue is also required for TNFalpha and IL-1alpha to stimulate p105 degradation...
  41. Carter R, Pennington K, Ungurait B, Ballard D. In vivo identification of inducible phosphoacceptors in the IKKgamma/NEMO subunit of human IkappaB kinase. J Biol Chem. 2003;278:19642-8 pubmed
    ..IKK contains two structurally related catalytic subunits termed IKKalpha and IKKbeta as well as a noncatalytic subunit called IKKgamma/NEMO...
  42. Poyet J, Srinivasula S, Lin J, Fernandes Alnemri T, Yamaoka S, Tsichlis P, et al. Activation of the Ikappa B kinases by RIP via IKKgamma /NEMO-mediated oligomerization. J Biol Chem. 2000;275:37966-77 pubmed
    ..Enforced oligomerization of the N terminus of IKKgamma or truncated IKKalpha or IKKbeta lacking their serine-cluster domains can also induce IKK and NF-kappaB activation...
  43. Zhang S, Kovalenko A, Cantarella G, Wallach D. Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation. Immunity. 2000;12:301-11 pubmed
    ..as well as recruitment of RIP to the receptor together with the three major signalosome components, NEMO, IKK1 and IKK2, and some kind of covalent modification of the recruited RIP molecules...
  44. Henkler F, Baumann B, Fotin Mleczek M, Weingärtner M, Schwenzer R, Peters N, et al. Caspase-mediated cleavage converts the tumor necrosis factor (TNF) receptor-associated factor (TRAF)-1 from a selective modulator of TNF receptor signaling to a general inhibitor of NF-kappaB activation. J Biol Chem. 2003;278:29216-30 pubmed
  45. Woronicz J, Gao X, Cao Z, Rothe M, Goeddel D. IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK. Science. 1997;278:866-9 pubmed
    ..Overexpression of a catalytically inactive form of IKK-beta blocked cytokine-induced NF-kappaB activation. Thus, an active IkappaB kinase complex may require three distinct protein kinases. ..
  46. Zhou H, Wertz I, O Rourke K, Ultsch M, Seshagiri S, Eby M, et al. Bcl10 activates the NF-kappaB pathway through ubiquitination of NEMO. Nature. 2004;427:167-71 pubmed
    ..Thus, the adaptor protein Bcl10 promotes activation of NF-kappaB transcription factors through paracaspase- and UBC13-dependent ubiquitination of NEMO. ..
  47. Wu L, Nakano H, Wu Z. The C-terminal activating region 2 of the Epstein-Barr virus-encoded latent membrane protein 1 activates NF-kappaB through TRAF6 and TAK1. J Biol Chem. 2006;281:2162-9 pubmed
    ..Thus, LMP1 utilizes two distinct pathways to activate NF-kappaB: a major one through CTAR2/TRAF6/TAK1/IKKbeta (canonical pathway) and a minor one through CTAR1/TRAF3/NIK/IKKalpha (noncanonical pathway).
  48. Ling L, Cao Z, Goeddel D. NF-kappaB-inducing kinase activates IKK-alpha by phosphorylation of Ser-176. Proc Natl Acad Sci U S A. 1998;95:3792-7 pubmed
    ..Conversely, a mutant form of IKK-alpha containing glutamic acid at residue 176 is constitutively active. Thus, the phosphorylation of IKK-alpha on Ser-176 by NIK may be required for cytokine-mediated NF-kappaB activation. ..
  49. Nemoto S, DiDonato J, Lin A. Coordinate regulation of IkappaB kinases by mitogen-activated protein kinase kinase kinase 1 and NF-kappaB-inducing kinase. Mol Cell Biol. 1998;18:7336-43 pubmed
    IkappaB kinases (IKKalpha and IKKbeta) are key components of the IKK complex that mediates activation of the transcription factor NF-kappaB in response to extracellular stimuli such as inflammatory cytokines, viral and bacterial ..
  50. Mercurio F, Murray B, Shevchenko A, Bennett B, Young D, Li J, et al. IkappaB kinase (IKK)-associated protein 1, a common component of the heterogeneous IKK complex. Mol Cell Biol. 1999;19:1526-38 pubmed
    ..multiprotein complex, the IkappaB kinase (IKK) signalsome, which contains two regulated IkappaB kinases, IKK1 and IKK2, that can each phosphorylate IkappaBalpha and IkappaBbeta...
  51. Sanz L, Sanchez P, Lallena M, Diaz Meco M, Moscat J. The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation. EMBO J. 1999;18:3044-53 pubmed
    ..of isozymes (zetaPKC and lambda/iotaPKC) are involved in the control of nuclear factor kappaB (NF-kappaB) through IKKbeta activation...
  52. Didonato J, Mercurio F, Rosette C, Wu Li J, SuYang H, Ghosh S, et al. Mapping of the inducible IkappaB phosphorylation sites that signal its ubiquitination and degradation. Mol Cell Biol. 1996;16:1295-304 pubmed
    ..As substitution of a conserved lysine residue slows down the ubiquitination and degradation of IkappaBalpha without affecting its phosphorylation, polyubiquitination is required for inducible IkappaB degradation. ..
  53. Criollo A, Senovilla L, Authier H, Maiuri M, Morselli E, Vitale I, et al. The IKK complex contributes to the induction of autophagy. EMBO J. 2010;29:619-31 pubmed publisher
    ..Altogether, these results indicate that IKK has a cardinal role in the stimulation of autophagy by physiological and pharmacological stimuli. ..
  54. Li X, Fang X, Gaynor R. Role of IKKgamma/nemo in assembly of the Ikappa B kinase complex. J Biol Chem. 2001;276:4494-500 pubmed
    ..When expressed alone following transfection, IKKalpha and IKKbeta were present in low molecular weight complexes migrating between 200 and 400 kDa...
  55. Wu Z, Shi Y, Tibbetts R, Miyamoto S. Molecular linkage between the kinase ATM and NF-kappaB signaling in response to genotoxic stimuli. Science. 2006;311:1141-6 pubmed
    ..Thus, regulated nuclear shuttling of NEMO links two signaling kinases, ATM and IKK, to activate NF-kappaB by genotoxic signals. ..
  56. Marienfeld R, Palkowitsch L, Ghosh S. Dimerization of the I kappa B kinase-binding domain of NEMO is required for tumor necrosis factor alpha-induced NF-kappa B activity. Mol Cell Biol. 2006;26:9209-19 pubmed
    ..corresponding to a six-amino-acid NEMO-binding domain from the C terminus of IkappaB kinase alpha (IKKalpha) and IKKbeta can disrupt the IKK complex and block NF-kappaB activation...
  57. Mangino G, Percario Z, Fiorucci G, Vaccari G, Manrique S, Romeo G, et al. In vitro treatment of human monocytes/macrophages with myristoylated recombinant Nef of human immunodeficiency virus type 1 leads to the activation of mitogen-activated protein kinases, IkappaB kinases, and interferon regulatory factor 3 and to the r. J Virol. 2007;81:2777-91 pubmed
    ..In addition, we have observed the activation of interferon regulatory factor 3, leading to the synthesis of beta interferon mRNA and protein, which in turn induces STAT2 phosphorylation. All of these effects require Nef myristoylation. ..
  58. Dan H, Cooper M, Cogswell P, Duncan J, Ting J, Baldwin A. Akt-dependent regulation of NF-{kappa}B is controlled by mTOR and Raptor in association with IKK. Genes Dev. 2008;22:1490-500 pubmed publisher
    ..The results provide insight into the effects of Akt/mTOR-dependent signaling on gene expression and into the therapeutic action of rapamycin. ..
  59. Takaesu G, Surabhi R, Park K, Ninomiya Tsuji J, Matsumoto K, Gaynor R. TAK1 is critical for IkappaB kinase-mediated activation of the NF-kappaB pathway. J Mol Biol. 2003;326:105-15 pubmed
    Cytokine treatment stimulates the IkappaB kinases, IKKalpha and IKKbeta, which phosphorylate the IkappaB proteins, leading to their degradation and activation of NF-kappaB regulated genes...
  60. Ebner K, Bandion A, Binder B, de Martin R, Schmid J. GMCSF activates NF-kappaB via direct interaction of the GMCSF receptor with IkappaB kinase beta. Blood. 2003;102:192-9 pubmed
    ..Fluorescence resonance energy transfer (FRET) microscopy confirmed the direct interaction of CFP-IKKbeta and YFPGMRalpha in living cells...
  61. Chen R, Ryzhakov G, Cooray S, Randow F, Smith G. Inhibition of IkappaB kinase by vaccinia virus virulence factor B14. PLoS Pathog. 2008;4:e22 pubmed publisher
    ..Notably, the interaction between B14 and the IKK complex required IKKbeta but not IKKalpha, suggesting the interaction occurs via IKKbeta...
  62. Lo Y, Maddineni U, Chung J, Rich R, Myszka D, Wu H. High-affinity interaction between IKKbeta and NEMO. Biochemistry. 2008;47:3109-16 pubmed publisher
    The Ser/Thr-specific IkappaB kinase (IKK), which comprises IKKalpha or IKKbeta and the regulatory protein NEMO, is at the bottleneck for NF-kappaB activation. IKK activity relies on interaction between NEMO and IKKalpha or IKKbeta...
  63. Tang E, Inohara N, Wang C, Nunez G, Guan K. Roles for homotypic interactions and transautophosphorylation in IkappaB kinase beta IKKbeta) activation [corrected]. J Biol Chem. 2003;278:38566-70 pubmed
    ..The IKK complex contains two catalytic subunits, IKKalpha and IKKbeta, and a noncatalytic subunit, NF-kappaB essential modifier/IKKgamma...
  64. Lee D, Kuo H, Chen C, Hsu J, Chou C, Wei Y, et al. IKK beta suppression of TSC1 links inflammation and tumor angiogenesis via the mTOR pathway. Cell. 2007;130:440-55 pubmed
    ..Here we show that IKKbeta, a major downstream kinase in the TNFalpha signaling pathway, physically interacts with and phosphorylates TSC1 ..
  65. Solt L, Madge L, Orange J, May M. Interleukin-1-induced NF-kappaB activation is NEMO-dependent but does not require IKKbeta. J Biol Chem. 2007;282:8724-33 pubmed
    ..and interleukin-1 (IL-1) requires the IkappaB kinase (IKK) complex, which contains two kinases named IKKalpha and IKKbeta and a critical regulatory subunit named NEMO...
  66. Xu G, Lo Y, Li Q, Napolitano G, Wu X, Jiang X, et al. Crystal structure of inhibitor of ?B kinase ?. Nature. 2011;472:325-30 pubmed publisher
    ..Other IKK family members, IKK?, TBK1 and IKK-i, may have a similar trimodular architecture and function...
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    The I kappa B kinase (IKK) complex, which is composed of the two kinases IKK alpha and IKK beta and the regulatory subunit IKK gamma/nuclear factor-kappa B (NF-kappa B) essential modulator (NEMO), is important in the cytokine-induced ..
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