Gene Symbol: IKBKE
Description: inhibitor of nuclear factor kappa B kinase subunit epsilon
Alias: IKK-E, IKK-i, IKKE, IKKI, inhibitor of nuclear factor kappa-B kinase subunit epsilon, I-kappa-B kinase epsilon, IKK-epsilon, IKK-related kinase epsilon, inducible I kappa-B kinase, inducible IkappaB kinase, inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon
Species: human
Products:     IKBKE

Top Publications

  1. Wang N, Ahmed S, Haqqi T. Genomic structure and functional characterization of the promoter region of human IkappaB kinase-related kinase IKKi/IKKvarepsilon gene. Gene. 2005;353:118-33 pubmed
    The inducible IkappaB kinase (IKKi/IKKepsilon) is a recently described serine-threonine kinase that activates the transcription factors NFkappaB, interferon regulatory factor-3 (IRF3) and CCAAA/enhancer-binding protein (C/EBPdelta)...
  2. Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, et al. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature. 2005;437:1167-72 pubmed
    ..Cardif thus functions as an adaptor, linking the cytoplasmic dsRNA receptor RIG-I to the initiation of antiviral programmes. ..
  3. Harris J, Oliere S, Sharma S, Sun Q, Lin R, Hiscott J, et al. Nuclear accumulation of cRel following C-terminal phosphorylation by TBK1/IKK epsilon. J Immunol. 2006;177:2527-35 pubmed
    ..These results illustrate a previously unrecognized aspect of cRel regulation, controlled by direct IKKepsilon/TBK1 phosphorylation. ..
  4. Guo B, Cheng G. Modulation of the interferon antiviral response by the TBK1/IKKi adaptor protein TANK. J Biol Chem. 2007;282:11817-26 pubmed
    ..adaptor inducing interferon-beta), and TRAF3 and downstream mediators TANK-binding kinase 1, inducible IkappaB kinase, and interferon regulatory factor 3...
  5. Peters R, Liao S, Maniatis T. IKKepsilon is part of a novel PMA-inducible IkappaB kinase complex. Mol Cell. 2000;5:513-22 pubmed
    Here we report the identification of a novel PMA-inducible IkappaB kinase complex, distinct from the well-characterized high-molecular weight IkappaB kinase complex containing IKKalpha, IKKbeta, and IKKgamma...
  6. Luron L, Saliba D, Blazek K, Lanfrancotti A, Udalova I. FOXO3 as a new IKK-?-controlled check-point of regulation of IFN-? expression. Eur J Immunol. 2012;42:1030-7 pubmed publisher
    ..Thus, we identify FOXO3 as a new IKK-?-controlled check-point of IRF activation and regulation of IFN-? expression, providing new insight into the role of FOXO3 in immune response control. ..
  7. Thurston T, Ryzhakov G, Bloor S, von Muhlinen N, Randow F. The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitin-coated bacteria. Nat Immunol. 2009;10:1215-21 pubmed publisher
    ..We conclude that human cells utilize the ubiquitin system and NDP52 to activate autophagy against bacteria attempting to colonize their cytosol. ..
  8. Ryzhakov G, Randow F. SINTBAD, a novel component of innate antiviral immunity, shares a TBK1-binding domain with NAP1 and TANK. EMBO J. 2007;26:3180-90 pubmed
    ..Activation of IRF3 requires its phosphorylation by TBK1 (TANK-binding kinase) or IKKi (inhibitor of nuclear factor kappaB kinase, inducible)...
  9. Ng M, Ho T, Kok K, Siu K, Li J, Jin D. MIP-T3 is a negative regulator of innate type I IFN response. J Immunol. 2011;187:6473-82 pubmed publisher
    ..Our findings suggest that MIP-T3 functions as a negative regulator of innate IFN response by preventing TRAF3 from forming protein complexes with critical downstream transducers and effectors. ..

More Information


  1. Fujita F, Taniguchi Y, Kato T, Narita Y, Furuya A, Ogawa T, et al. Identification of NAP1, a regulatory subunit of IkappaB kinase-related kinases that potentiates NF-kappaB signaling. Mol Cell Biol. 2003;23:7780-93 pubmed
    ..Here we identify NAP1 (for NAK-associated protein 1), a protein that interacts with NAK and its relative IKK epsilon (also known as IKKi). NAP1 activates NAK and facilitates its oligomerization...
  2. Gao L, Coope H, Grant S, Ma A, Ley S, Harhaj E. ABIN1 protein cooperates with TAX1BP1 and A20 proteins to inhibit antiviral signaling. J Biol Chem. 2011;286:36592-602 pubmed publisher
    ..molecule TAX1BP1 and was essential for the recruitment of TAX1BP1 and A20 to the noncanonical I?B kinases TBK1 and IKKi in response to poly(I:C) transfection...
  3. Shen R, Zhou A, Kim E, Lim E, Habelhah H, Hahn W. I?B kinase ? phosphorylates TRAF2 to promote mammary epithelial cell transformation. Mol Cell Biol. 2012;32:4756-68 pubmed publisher
    ..I?B kinase ? (IKK?; IKKi, encoded by IKBKE) is a breast oncogene that is amplified in 30% of breast cancers and drives transformation in an NF-?B-dependent ..
  4. Boehm J, Zhao J, Yao J, Kim S, Firestein R, Dunn I, et al. Integrative genomic approaches identify IKBKE as a breast cancer oncogene. Cell. 2007;129:1065-79 pubmed
    ..Whole genome structural analyses reveal that one of these kinases, IKBKE (IKKepsilon), is amplified and overexpressed in breast cancer cell lines and patient-derived tumors...
  5. Zhao T, Yang L, Sun Q, Arguello M, Ballard D, Hiscott J, et al. The NEMO adaptor bridges the nuclear factor-kappaB and interferon regulatory factor signaling pathways. Nat Immunol. 2007;8:592-600 pubmed
    ..IRF3 phosphorylation and interferon production were restored by ectopic expression of NEMO. Thus, NEMO, like MAVS, acts as an adaptor protein that allows RIG-I to activate both the NF-kappaB and IRF signaling pathways. ..
  6. Chau T, Gioia R, Gatot J, Patrascu F, Carpentier I, Chapelle J, et al. Are the IKKs and IKK-related kinases TBK1 and IKK-epsilon similarly activated?. Trends Biochem Sci. 2008;33:171-80 pubmed publisher
    ..Moreover, increasing evidence indicates that distinct scaffold proteins assemble IKK, and potentially TBK1 and IKK-epsilon subcomplexes, in a stimulus-specific manner, which might be a mechanism to achieve specificity. ..
  7. Friedman C, O Donnell M, Legarda Addison D, Ng A, Cardenas W, Yount J, et al. The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response. EMBO Rep. 2008;9:930-6 pubmed publisher
    ..These findings show that CYLD is a negative regulator of RIG-I-mediated innate antiviral response. ..
  8. Schröder M, Baran M, Bowie A. Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKepsilon-mediated IRF activation. EMBO J. 2008;27:2147-57 pubmed publisher
    ..Therefore, this study shows for the first time the involvement of a DEAD box helicase in TBK1/IKKepsilon-mediated IRF activation and Ifnb promoter induction. ..
  9. Péant B, Forest V, Trudeau V, Latour M, Mes Masson A, Saad F. I?B-Kinase-? (IKK?/IKKi/I?BK?) expression and localization in prostate cancer tissues. Prostate. 2011;71:1131-8 pubmed publisher
    ..Finally, we found a strong link between an increase of IKK? cytoplasmic expression in PCa and metastatic progression. This study strongly suggests the role of IKK? as a PCa oncogene that may be involved in the emergence of a CR state. ..
  10. Huang J, Liu T, Xu L, Chen D, Zhai Z, Shu H. SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways. EMBO J. 2005;24:4018-28 pubmed
    ..These findings suggest that SIKE is a physiological suppressor of IKKepsilon and TBK1 and plays an inhibitory role in virus- and TLR3-triggered IRF-3 but not NF-kappaB activation pathways. ..
  11. Adli M, Baldwin A. IKK-i/IKKepsilon controls constitutive, cancer cell-associated NF-kappaB activity via regulation of Ser-536 p65/RelA phosphorylation. J Biol Chem. 2006;281:26976-84 pubmed
    ..The data indicate a role for IKK-i/IKKepsilon in controlling proliferation of certain cancer cells through regulation of constitutive NF-kappaB activity. ..
  12. Xie X, Zhang D, Zhao B, Lu M, You M, Condorelli G, et al. IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct phosphorylation. Proc Natl Acad Sci U S A. 2011;108:6474-9 pubmed publisher
    ..Our observations suggest a physiological function of IKK?/TBK1 in AKT regulation and a possible mechanism of IKK?/TBK1 in oncogenesis by activating AKT. ..
  13. Fitzgerald K, McWhirter S, Faia K, Rowe D, Latz E, Golenbock D, et al. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol. 2003;4:491-6 pubmed
    ..Thus, IKKepsilon and TBK1 have a pivotal role in coordinating the activation of IRF3 and NF-kappaB in the innate immune response. ..
  14. Guo J, Shu S, He L, Lee Y, Kruk P, Grenman S, et al. Deregulation of IKBKE is associated with tumor progression, poor prognosis, and cisplatin resistance in ovarian cancer. Am J Pathol. 2009;175:324-33 pubmed publisher
    I-kappa-B kinase e (IKBKE; IKKepsilon) has been recently identified as a breast cancer oncogene, and its alteration appears to be an early event in breast cancer development...
  15. Dieguez Gonzalez R, Akar S, Calaza M, Perez Pampin E, Costas J, Torres M, et al. Genetic variation in the nuclear factor kappaB pathway in relation to susceptibility to rheumatoid arthritis. Ann Rheum Dis. 2009;68:579-83 pubmed publisher
    ..of 17 core genes of the NFkappaB pathway (REL, RELA, RELB, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, IKBKA, IKBKB, IKBKE, IKBKAP, KBRAS1, KBRAS2, MAP3K1, MAP3K14, TAX1BP1) were studied by mass spectrometry analysis complemented with 5'-..
  16. Paz S, Vilasco M, Arguello M, Sun Q, Lacoste J, Nguyen T, et al. Ubiquitin-regulated recruitment of IkappaB kinase epsilon to the MAVS interferon signaling adapter. Mol Cell Biol. 2009;29:3401-12 pubmed publisher
    ..These results provide further support for the differential role of IKKepsilon and TBK-1 in the RIG-I/Mda5 pathway. ..
  17. Hutti J, Shen R, Abbott D, Zhou A, Sprott K, Asara J, et al. Phosphorylation of the tumor suppressor CYLD by the breast cancer oncogene IKKepsilon promotes cell transformation. Mol Cell. 2009;34:461-72 pubmed publisher
    ..Together, these observations define IKKepsilon and CYLD as an oncogene-tumor suppressor network that participates in tumorigenesis. ..
  18. Shimada T, Kawai T, Takeda K, Matsumoto M, Inoue J, Tatsumi Y, et al. IKK-i, a novel lipopolysaccharide-inducible kinase that is related to IkappaB kinases. Int Immunol. 1999;11:1357-62 pubmed
    ..These results suggest that IKK-i is an inducible IkappaB kinase which may play a special role in the immune response.
  19. Kishore N, Huynh Q, Mathialagan S, Hall T, Rouw S, Creely D, et al. IKK-i and TBK-1 are enzymatically distinct from the homologous enzyme IKK-2: comparative analysis of recombinant human IKK-i, TBK-1, and IKK-2. J Biol Chem. 2002;277:13840-7 pubmed
    ..Thus, although these IKKs are structurally similar, their enzymatic properties may provide insights into their unique functions. ..
  20. Martin B, Wang C, Willette Brown J, Herjan T, Gulen M, Zhou H, et al. IKK? negatively regulates ASC-dependent inflammasome activation. Nat Commun. 2014;5:4977 pubmed publisher
    ..Mechanistically, the downstream nuclear effector IKK-related kinase (IKKi) facilitates translocation of ASC from the nucleus to the perinuclear area during inflammasome activation...
  21. Buss H, Dörrie A, Schmitz M, Hoffmann E, Resch K, Kracht M. Constitutive and interleukin-1-inducible phosphorylation of p65 NF-{kappa}B at serine 536 is mediated by multiple protein kinases including I{kappa}B kinase (IKK)-{alpha}, IKK{beta}, IKK{epsilon}, TRAF family member-associated (TANK)-binding kinase 1. J Biol Chem. 2004;279:55633-43 pubmed
  22. Hiscott J, Lacoste J, Lin R. Recruitment of an interferon molecular signaling complex to the mitochondrial membrane: disruption by hepatitis C virus NS3-4A protease. Biochem Pharmacol. 2006;72:1477-84 pubmed
    ..Cys508Ala) is not cleaved from the mitochondria by active protease; and (4) the virus-induced IKK epsilon kinase, but not TBK1, co-localizes strongly with MAVS at the mitochondrial membrane and the localization of ..
  23. Hsu S, Kim M, Hernandez L, Grajales V, NOONAN A, Anver M, et al. IKK-ε coordinates invasion and metastasis of ovarian cancer. Cancer Res. 2012;72:5494-504 pubmed publisher
    ..Inhibition of IKK-ε signaling thus emerges as a viable therapeutic strategy in women whose ovarian cancer shows aberrant activation of this pathway. ..
  24. Nan J, Du Y, Chen X, Bai Q, Wang Y, Zhang X, et al. TPCA-1 is a direct dual inhibitor of STAT3 and NF-?B and regresses mutant EGFR-associated human non-small cell lung cancers. Mol Cancer Ther. 2014;13:617-29 pubmed publisher
    ..Therefore, synergistic treatment of TPCA-1 with TKIs has potential to be a more effective strategy for cancers. ..
  25. Fernandez G, Zaikos T, Khan S, Jacobi A, Behlke M, Zeichner S. Targeting I?B proteins for HIV latency activation: the role of individual I?B and NF-?B proteins. J Virol. 2013;87:3966-78 pubmed publisher
    ..I?B? knockdown may offer attractive therapeutic advantages for HIV activation because it is not essential for mammalian growth and development and because new siRNA delivery strategies may target siRNAs to HIV latently infected cells. ..
  26. Péant B, Gilbert S, Le Page C, Poisson A, L Ecuyer E, Boudhraa Z, et al. I?B-Kinase-epsilon (IKK?) over-expression promotes the growth of prostate cancer through the C/EBP-? dependent activation of IL-6 gene expression. Oncotarget. 2017;8:14487-14501 pubmed publisher
    ..We have previously established that over-expression of I-kappa-B-kinase-epsilon (IKK? also named IKKi or I?BK?) in hormone-sensitive prostate cancer cell lines induces IL-6 secretion...
  27. Chau T, Göktuna S, Rammal A, Casanova T, Duong H, Gatot J, et al. A role for APPL1 in TLR3/4-dependent TBK1 and IKKε activation in macrophages. J Immunol. 2015;194:3970-83 pubmed publisher
    ..Those signaling pathways involve the signal-induced degradation of APPL1 to prevent aberrant IRF3-dependent gene expression linked to immune diseases. ..
  28. Hommers L, Raab A, Bohl A, Weber H, Scholz C, Erhardt A, et al. MicroRNA hsa-miR-4717-5p regulates RGS2 and may be a risk factor for anxiety-related traits. Am J Med Genet B Neuropsychiatr Genet. 2015;168B:296-306 pubmed publisher
    ..showed the most robust effect on RGS2 and regulated two other candidate genes of anxiety disorders (CNR1 and IKBKE) as well...
  29. Harquail J, Leblanc N, Landry C, Crapoulet N, Robichaud G. Pax-5 Inhibits NF-?B Activity in Breast Cancer Cells Through IKK? and miRNA-155 Effectors. J Mammary Gland Biol Neoplasia. 2018;23:177-187 pubmed publisher
    ..Through the conditional expression of microRNA-155 in breast cancer models, we identify and validate IKK? (IKBKE) as a downstream target and an essential effector of Pax-5-mediated suppression of NF-?B signaling...
  30. Sgarbanti M, Marsili G, Remoli A, Stellacci E, Mai A, Rotili D, et al. I?B kinase ? targets interferon regulatory factor 1 in activated T lymphocytes. Mol Cell Biol. 2014;34:1054-65 pubmed publisher
    ..These results demonstrate that TCR/CD28 stimulation of primary T cells stimulates IKK-? activation, which in turn contributes to suppression of IFN-? production. ..
  31. Breiman A, Grandvaux N, Lin R, Ottone C, Akira S, Yoneyama M, et al. Inhibition of RIG-I-dependent signaling to the interferon pathway during hepatitis C virus expression and restoration of signaling by IKKepsilon. J Virol. 2005;79:3969-78 pubmed
    ..The partial restoration of the capacity of the host cell to transcribe IFN-beta indicates that IKKepsilon expression is able to bypass the HCV-mediated inhibition and restore the innate antiviral response. ..
  32. Challa S, Guo J, Ding X, Xu C, Li Y, Kim D, et al. IKBKE Is a Substrate of EGFR and a Therapeutic Target in Non-Small Cell Lung Cancer with Activating Mutations of EGFR. Cancer Res. 2016;76:4418-29 pubmed publisher
    ..Here we report support for a rationale to target IKBKE, an I?B kinase family member that activates the AKT and NF-?B pathways, as one strategy to address NSCLC resistant ..
  33. Charoenthongtrakul S, Gao L, Parvatiyar K, Lee D, Harhaj E. RING finger protein 11 targets TBK1/IKKi kinases to inhibit antiviral signaling. PLoS ONE. 2013;8:e53717 pubmed publisher
    ..RNF11 interacted with the noncanonical IKK kinases TBK1/IKKi and attenuated their Lys63-linked polyubiquitination by blocking interactions with the E3 ligase TRAF3...
  34. Sarmiento Salinas F, Santillán Benítez J, Hernández Navarro M, Mendieta Zerón H. NF-κB1/IKKε Gene Expression and Clinical Activity in Patients With Rheumatoid Arthritis. Lab Med. 2017;49:11-17 pubmed publisher
    ..The objective of this study was to evaluate whether there was an association between nuclear factor kappa beta1/IKK epsilon (NF-κB1/IKKε) gene expression and clinical activity in RA...
  35. Sato M, Sato K, Tomura K, Kosako H, Sato K. The autophagy receptor ALLO-1 and the IKKE-1 kinase control clearance of paternal mitochondria in Caenorhabditis elegans. Nat Cell Biol. 2018;20:81-91 pubmed publisher
    ..We also identified IKKE-1, a worm homologue of the TBK1 and IKK? family kinase, as another critical regulator of allophagy...
  36. Tian Y, Hao S, YE M, Zhang A, Nan Y, Wang G, et al. MicroRNAs let-7b/i suppress human glioma cell invasion and migration by targeting IKBKE directly. Biochem Biophys Res Commun. 2015;458:307-12 pubmed publisher
    We demonstrated that IKBKE is overexpressed in human gliomas and that the downregulation of IKBKE markedly inhibits the proliferative and invasive abilities of glioma cells, which is consistent with the results reported by several ..
  37. Wang C, Huang Y, Sheng J, Huang H, Zhou J. Estrogen receptor alpha inhibits RLR-mediated immune response via ubiquitinating TRAF3. Cell Signal. 2015;27:1977-83 pubmed publisher
    ..Thus, ERα functions as a negative feedback regulator of RLR-triggered antiviral immune responses. These findings also provide the insights that separate the immune effects of ERα from its ligand-induced hormonal effects. ..
  38. Niederberger E, Moser C, Kynast K, Geisslinger G. The non-canonical I?B kinases IKK? and TBK1 as potential targets for the development of novel therapeutic drugs. Curr Mol Med. 2013;13:1089-97 pubmed
    ..In this review, we summarize the roles of IKK? and TBK1 in different diseases and outline therapeutic options for modulation of these kinases. ..
  39. Lin R, Lacoste J, Nakhaei P, Sun Q, Yang L, Paz S, et al. Dissociation of a MAVS/IPS-1/VISA/Cardif-IKKepsilon molecular complex from the mitochondrial outer membrane by hepatitis C virus NS3-4A proteolytic cleavage. J Virol. 2006;80:6072-83 pubmed publisher
    ..These observations provide an outline of the mechanism by which hepatitis C virus evades the interferon antiviral response...
  40. Wang H, Ryu W. Hepatitis B virus polymerase blocks pattern recognition receptor signaling via interaction with DDX3: implications for immune evasion. PLoS Pathog. 2010;6:e1000986 pubmed publisher
    ..A therapeutic implication of this work is that a strategy to interfere with the HBV Pol-DDX3 interaction might lead to the resolution of life-long persistent infection...
  41. Fang R, Jiang Q, Zhou X, Wang C, Guan Y, Tao J, et al. MAVS activates TBK1 and IKK? through TRAFs in NEMO dependent and independent manner. PLoS Pathog. 2017;13:e1006720 pubmed publisher
    ..Moreover, individual TRAFs differently mediated TBK1/IKK? activation and thus fine-tuned antiviral immunity under physiological conditions. ..
  42. Angleró Rodríguez Y, Pantoja P, Sariol C. Dengue virus subverts the interferon induction pathway via NS2B/3 protease-IκB kinase epsilon interaction. Clin Vaccine Immunol. 2014;21:29-38 pubmed publisher
    ..This observation is supported by the DENV-associated inhibition of the kinase activity of IKKε. Our data identify IKKε as a novel target of DENV NS2B/3 protease. ..
  43. Liang Q, Fu B, Wu F, Li X, Yuan Y, ZHU F. ORF45 of Kaposi's sarcoma-associated herpesvirus inhibits phosphorylation of interferon regulatory factor 7 by IKK? and TBK1 as an alternative substrate. J Virol. 2012;86:10162-72 pubmed publisher
    ..We demonstrated that ORF45 competes with the associated IRF7 and inhibits its phosphorylation by IKK? or TBK1 by acting as an alternative substrate. ..
  44. Aupperle K, Yamanishi Y, Bennett B, Mercurio F, Boyle D, Firestein G. Expression and regulation of inducible IkappaB kinase (IKK-i) in human fibroblast-like synoviocytes. Cell Immunol. 2001;214:54-9 pubmed
    ..Recently, a novel inducible IkappaB kinase has been described, namely, IKK-i or IKK-epsilon, which is functionally and structurally distinct from ..
  45. He Z, Zhao J, Zhang J, Jung J, Feng P. NF-?B activation coordinated by IKK? and IKK? enables latent infection of Kaposi's sarcoma-associated herpesvirus. J Virol. 2014;88:444-55 pubmed publisher
    ..Our findings uncover a scheme wherein NF-?B activation is coordinated by IKK? and IKK?, which sequentially phosphorylate RelA in a site-specific manner to enable latent infection after KSHV de novo infection. ..
  46. Unterholzner L, Sumner R, Baran M, Ren H, Mansur D, Bourke N, et al. Vaccinia virus protein C6 is a virulence factor that binds TBK-1 adaptor proteins and inhibits activation of IRF3 and IRF7. PLoS Pathog. 2011;7:e1002247 pubmed publisher
    ..Thus C6 contributes to VACV virulence and might do so via the inhibition of PRR-induced activation of IRF3 and IRF7. ..
  47. Guo J, Kim D, Gao J, Kurtyka C, Chen H, Yu C, et al. IKBKE is induced by STAT3 and tobacco carcinogen and determines chemosensitivity in non-small cell lung cancer. Oncogene. 2013;32:151-9 pubmed publisher
    Serine/threonine kinase IKBKE is a newly identified oncogene; however, its regulation remains elusive...
  48. Ryzhakov G, Blazek K, Lai C, Udalova I. IL-17 receptor adaptor protein Act1/CIKS plays an evolutionarily conserved role in antiviral signaling. J Immunol. 2012;189:4852-8 pubmed publisher
    ..On the whole, our study demonstrates that Act1 is a component of antiviral signaling. ..
  49. Zhou A, Shen R, Kim E, Lock Y, Xu M, Chen Z, et al. IKK?-mediated tumorigenesis requires K63-linked polyubiquitination by a cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex. Cell Rep. 2013;3:724-33 pubmed publisher
    I?B kinase ? (IKK?, IKBKE) is a key regulator of innate immunity and a breast cancer oncogene, amplified in ~30% of breast cancers, that promotes malignant transformation through NF-?B activation...
  50. Panagodage S, Yong H, da Silva Costa F, Borg A, Kalionis B, Brennecke S, et al. Low-Dose Acetylsalicylic Acid Treatment Modulates the Production of Cytokines and Improves Trophoblast Function in an in Vitro Model of Early-Onset Preeclampsia. Am J Pathol. 2016;186:3217-3224 pubmed publisher
    ..PE serum-induced increases in the apoptotic markers P53 mRNA expression, IKBKE mRNA expression, caspase 3 activity, and decreased BIRC8 mRNA expression, were attenuated by LDA treatment...
  51. Sweeney S, Mo L, Firestein G. Antiviral gene expression in rheumatoid arthritis: role of IKKepsilon and interferon regulatory factor 3. Arthritis Rheum. 2007;56:743-52 pubmed
    ..These findings indicate that the IKKepsilon pathway may have potential as a therapeutic target in RA. ..
  52. Diani E, Avesani F, Bergamo E, Cremonese G, Bertazzoni U, Romanelli M. HTLV-1 Tax protein recruitment into IKKε and TBK1 kinase complexes enhances IFN-I expression. Virology. 2015;476:92-99 pubmed publisher
    ..We propose that Tax may be recruited into the TBK1/IKKÉ› complexes as a scaffolding-adaptor protein that enhances IFN-I gene expression. ..
  53. Liu Y, Lu J, Zhang Z, Zhu L, Dong S, Guo G, et al. Amlexanox, a selective inhibitor of IKBKE, generates anti-tumoral effects by disrupting the Hippo pathway in human glioblastoma cell lines. Cell Death Dis. 2017;8:e3022 pubmed publisher
    ..Furthermore, we found that amlexanox altered the protein expression of the Hippo pathway by downregulating IKBKE. Our data indicates that IKBKE directly targets LATS1/2 and induces degradation of LATS1/2, thereby inhibiting the ..
  54. Zhang W, Zhang X, Wu X, He L, Zeng X, Crammer A, et al. Competition between TRAF2 and TRAF6 regulates NF-kappaB activation in human B lymphocytes. Chin Med Sci J. 2010;25:1-12 pubmed
    ..TRAF2 induced activity of IkappaB-kinases (IKKalpha, IKKi/epsilon), phosphorylation of IkappaBalpha, as well as nuclear translocation and phosphorylation of p65/RelA...
  55. Lu J, Yang Y, Guo G, Liu Y, Zhang Z, Dong S, et al. IKBKE regulates cell proliferation and epithelial-mesenchymal transition of human malignant glioma via the Hippo pathway. Oncotarget. 2017;8:49502-49514 pubmed publisher
    b>IKBKE is increased in several types of cancers and is associated with tumour malignancy. In this study, we confirmed that IKBKE promoted glioma proliferation, migration and invasion in vitro...
  56. Doyle S, Shirey K, McGettrick A, Kenny E, Carpenter S, Caffrey B, et al. Nuclear factor ?B2 p52 protein has a role in antiviral immunity through I?B kinase epsilon-dependent induction of Sp1 protein and interleukin 15. J Biol Chem. 2013;288:25066-75 pubmed publisher
    ..Our study identifies NF?B2 as a target for IKK? in antiviral immunity and describes, for the first time, a role for NF?B2 in the regulation of gene expression in response to viral infection. ..
  57. Huang W, Liang Y, Dong J, Zhou L, Gao C, Jiang C, et al. SUMO E3 Ligase PIASy Mediates High Glucose-Induced Activation of NF-?B Inflammatory Signaling in Rat Mesangial Cells. Mediators Inflamm. 2017;2017:1685194 pubmed publisher
    ..However, the association of PIASy and NF-?B signaling in the pathogenesis of diabetic nephropathy (DN) has not been defined...
  58. Zhang Z, Lu J, Guo G, Yang Y, Dong S, Liu Y, et al. IKBKE promotes glioblastoma progression by establishing the regulatory feedback loop of IKBKE/YAP1/miR-Let-7b/i. Tumour Biol. 2017;39:1010428317705575 pubmed publisher
    Recently, we have demonstrated that IKBKE (inhibitor of nuclear factor kappa-B kinase subunit epsilon) is overexpressed in human glioblastoma and that inhibition of IKBKE remarkably suppresses the proliferative and invasive behaviour of ..
  59. Saitoh T, Yamamoto M, Miyagishi M, Taira K, Nakanishi M, Fujita T, et al. A20 is a negative regulator of IFN regulatory factor 3 signaling. J Immunol. 2005;174:1507-12 pubmed
    ..Our study thus demonstrates that A20 is a candidate negative regulator of the signaling cascade to IRF-3 activation in the innate antiviral response. ..
  60. Kim H, Seed B. The transcription factor MafB antagonizes antiviral responses by blocking recruitment of coactivators to the transcription factor IRF3. Nat Immunol. 2010;11:743-50 pubmed publisher
    ..Higher expression of MafB in human pancreatic islet beta cells might increase cellular vulnerability to viral infections associated with the etiology of type 1 diabetes. ..
  61. Williams V, Grosset A, Zamorano Cuervo N, St Pierre Y, Sylvestre M, Gaboury L, et al. Detection of IKKε by immunohistochemistry in primary breast cancer: association with EGFR expression and absence of lymph node metastasis. BMC Cancer. 2017;17:356 pubmed publisher
    ..This study suggests that breast cancer tumors expressing EGFR and IKKε may be potential targets for drugs aiming at inhibiting IKKε activity or expression. ..
  62. Grandvaux N. [The IKK? kinase in breast cancer: from oncogenesis to treatment resistance]. Med Sci (Paris). 2011;27:619-25 pubmed publisher
    ..Interestingly, IKK? is involved in the development of resistance to Tamoxifène. Thus, IKK? is a promising therapeutic target for newly developed breast cancer treatment. ..
  63. Li Q, Sun H, Zou J, Ge C, Yu K, Cao Y, et al. Increased expression of estrogen receptor ?-36 by breast cancer oncogene IKK? promotes growth of ER-negative breast cancer cells. Cell Physiol Biochem. 2013;31:833-41 pubmed publisher
    ..Moreover, IKK? enhanced the growth of MDA-MB-231 and MDA-MB-436 cells. These results suggest that IKK? increases ER?-36 expression and is involved in ER?-36 mediated non-genomic estrogen signaling. ..
  64. Gu L, Fullam A, BRENNAN R, Schröder M. Human DEAD box helicase 3 couples I?B kinase ? to interferon regulatory factor 3 activation. Mol Cell Biol. 2013;33:2004-15 pubmed publisher
    ..Our data implicates DDX3 as a scaffolding adaptor that directly facilitates phosphorylation of IRF3 by IKK?. DDX3 might thus be involved in pathway-specific activation of IRF3. ..
  65. Prins K, C rdenas W, Basler C. Ebola virus protein VP35 impairs the function of interferon regulatory factor-activating kinases IKKepsilon and TBK-1. J Virol. 2009;83:3069-77 pubmed publisher
  66. Vijayan M, Xia C, Song Y, Ngo H, Studstill C, Drews K, et al. Sphingosine 1-Phosphate Lyase Enhances the Activation of IKK? To Promote Type I IFN-Mediated Innate Immune Responses to Influenza A Virus Infection. J Immunol. 2017;199:677-687 pubmed publisher
    ..This indicates that IKK? is crucial for SPL-mediated inhibition of influenza virus replication. Thus, the results illustrate the functional significance of the SPL-IKK?-IFN axis during host innate immunity against viral infection. ..
  67. Renner F, Moreno R, Schmitz M. SUMOylation-dependent localization of IKKepsilon in PML nuclear bodies is essential for protection against DNA-damage-triggered cell death. Mol Cell. 2010;37:503-15 pubmed publisher
    ..SUMO modification of IKKepsilon is required to trigger phosphorylation of nuclear substrates including NF-kappaB p65, thereby contributing to the antiapoptotic function of NF-kappaB in response to DNA damage. ..
  68. Cheng A, Guo J, Henderson Jackson E, Kim D, Malafa M, Coppola D. I?B Kinase ? expression in pancreatic ductal adenocarcinoma. Am J Clin Pathol. 2011;136:60-6 pubmed publisher
    ..In addition, IKK? could serve as a prognostic marker and potential therapeutic target for PDA intervention. ..
  69. Gatot J, Gioia R, Chau T, Patrascu F, Warnier M, Close P, et al. Lipopolysaccharide-mediated interferon regulatory factor activation involves TBK1-IKKepsilon-dependent Lys(63)-linked polyubiquitination and phosphorylation of TANK/I-TRAF. J Biol Chem. 2007;282:31131-46 pubmed
  70. Liu X, Chen W, Wei B, Shan Y, Wang C. IFN-induced TPR protein IFIT3 potentiates antiviral signaling by bridging MAVS and TBK1. J Immunol. 2011;187:2559-68 pubmed publisher
    ..Collectively, our study characterizes IFIT3 as an important modulator in innate immunity, revealing a new function of the IFIT family proteins (IFN-induced protein with tetratricopeptide repeats). ..
  71. Wang S, Xie F, Chu F, Zhang Z, Yang B, Dai T, et al. YAP antagonizes innate antiviral immunity and is targeted for lysosomal degradation through IKK?-mediated phosphorylation. Nat Immunol. 2017;18:733-743 pubmed publisher
  72. Kaukinen P, Sillanpää M, Nousiainen L, Melen K, Julkunen I. Hepatitis C virus NS2 protease inhibits host cell antiviral response by inhibiting IKK? and TBK1 functions. J Med Virol. 2013;85:71-82 pubmed publisher
    ..The present study identified HCV NS2 as a potent interferon antagonist, and describes an explanation of how NS2 downregulates the major signaling pathways involved in the development of host innate antiviral responses. ..
  73. Ku X, Heinzlmeir S, Liu X, Médard G, Kuster B. A new chemical probe for quantitative proteomic profiling of fibroblast growth factor receptor and its inhibitors. J Proteomics. 2014;96:44-55 pubmed publisher
    ..of the two inhibitors confirming many of the previously identified (off-) targets such as AURKA, FLT4-VEGFR3, IKBKE and PDGFR?...
  74. Lee S, Hong M, Cho J, Lee J, Kim K. IKK? and TBK1 expression in gastric cancer. Oncotarget. 2017;8:16233-16242 pubmed publisher
    ..The role of IKK? and TBK1 in intestinal-type gastric cancer pathogenesis should be elucidated by further investigation. ..
  75. Minami S, Ito K, Honma M, Ikebuchi Y, Anzai N, Kanai Y, et al. Posttranslational regulation of Abcc2 expression by SUMOylation system. Am J Physiol Gastrointest Liver Physiol. 2009;296:G406-13 pubmed publisher
    ..all of these interactions were abolished by substituting the putative SUMO consensus site in the linker region (IKKE) in Abcc2 to IRKE...
  76. Gringhuis S, Kaptein T, Wevers B, Mesman A, Geijtenbeek T. Fucose-specific DC-SIGN signalling directs T helper cell type-2 responses via IKK?- and CYLD-dependent Bcl3 activation. Nat Commun. 2014;5:3898 pubmed publisher
  77. Qu F, Gao H, Zhu S, Shi P, Zhang Y, Liu Y, et al. TRAF6-dependent Act1 phosphorylation by the I?B kinase-related kinases suppresses interleukin-17-induced NF-?B activation. Mol Cell Biol. 2012;32:3925-37 pubmed publisher
    ..Recently, inducible I?B kinase (IKKi) has been shown to phosphorylate Act1 on Ser 311 to mediate IL-17-induced mRNA stability...
  78. Schoenemeyer A, Barnes B, Mancl M, Latz E, Goutagny N, Pitha P, et al. The interferon regulatory factor, IRF5, is a central mediator of toll-like receptor 7 signaling. J Biol Chem. 2005;280:17005-12 pubmed
    ..IRF5 and IRF7, therefore, emerge from these studies as critical mediators of TLR7 signaling. ..
  79. Lee S, Jhun J, Byun J, Kim E, Jung K, Lee J, et al. IL-17 axis accelerates the inflammatory progression of obese in mice via TBK1 and IKBKE pathway. Immunol Lett. 2017;184:67-75 pubmed publisher
    ..The inhibition of TBK1 and the inhibition of I IKBKE reduces inflammatory response and improves obesity...
  80. Oshiumi H, Miyashita M, Matsumoto M, Seya T. A distinct role of Riplet-mediated K63-Linked polyubiquitination of the RIG-I repressor domain in human antiviral innate immune responses. PLoS Pathog. 2013;9:e1003533 pubmed publisher
    ..In conclusion, our results establish that Riplet-mediated K63-linked polyubiquitination released RIG-I RD autorepression, which allowed the access of positive factors to the RIG-I protein. ..
  81. Mukawera E, Chartier S, Williams V, Pagano P, Lapointe R, Grandvaux N. Redox-modulating agents target NOX2-dependent IKKε oncogenic kinase expression and proliferation in human breast cancer cell lines. Redox Biol. 2015;6:9-18 pubmed publisher
    ..Taken together, our results suggest that redox-modulating compounds targeting NOX2 could present a particular therapeutic interest in combination therapy against breast carcinomas exhibiting IKKε amplification. ..
  82. Peng Y, Xu R, Zheng X. HSCARG negatively regulates the cellular antiviral RIG-I like receptor signaling pathway by inhibiting TRAF3 ubiquitination via recruiting OTUB1. PLoS Pathog. 2014;10:e1004041 pubmed publisher
    ..This study demonstrated that HSCARG is a negative regulator that enables balanced antiviral innate immunity. ..
  83. Guan H, Zhang H, Cai J, Wu J, Yuan J, Li J, et al. IKBKE is over-expressed in glioma and contributes to resistance of glioma cells to apoptosis via activating NF-?B. J Pathol. 2011;223:436-45 pubmed publisher
    I?B kinase-? (IKBKE), a member of the I?B kinase (IKK) family, has been identified as an oncogenic protein and found to be up-regulated in breast cancer, ovarian cancer and prostate cancer...
  84. Heilker R, Freuler F, Pulfer R, Di Padova F, Eder J. All three IkappaB isoforms and most Rel family members are stably associated with the IkappaB kinase 1/2 complex. Eur J Biochem. 1999;259:253-61 pubmed
    ..Therefore, both p90rsk1 and CK II have the same preference for phosphorylating only one of the two serines which are relevant for inducible degradation. ..
  85. Thomas R, Sos M, Zander T, Mani O, Popov A, Berenbrinker D, et al. Inhibition of nuclear translocation of nuclear factor-kappaB despite lack of functional IkappaBalpha protein overcomes multiple defects in apoptosis signaling in human B-cell malignancies. Clin Cancer Res. 2005;11:8186-94 pubmed
    ..Thus, targeting IkappaB kinases may represent an attractive therapeutic approach against these malignancies regardless of the mutational status of IkappaBalpha. ..
  86. Nakhaei P, Sun Q, Solis M, Mesplede T, Bonneil E, Paz S, et al. I?B kinase ?-dependent phosphorylation and degradation of X-linked inhibitor of apoptosis sensitizes cells to virus-induced apoptosis. J Virol. 2012;86:726-37 pubmed publisher
    ..Our findings reveal a novel function of IKK? as a regulator of the virus-induced triggering of apoptosis via the phosphorylation-dependent turnover of XIAP. ..
  87. Chariot A, Leonardi A, Muller J, Bonif M, Brown K, Siebenlist U. Association of the adaptor TANK with the I kappa B kinase (IKK) regulator NEMO connects IKK complexes with IKK epsilon and TBK1 kinases. J Biol Chem. 2002;277:37029-36 pubmed
    ..TANK was previously shown to assist NF-kappa B activation in a complex with TANK-binding kinase 1 (TBK1) or IKK epsilon, two kinases distantly related to IKK alpha/beta, but the underlying mechanisms remained unknown...
  88. Belova S, Shenkman B, Kostrominova T, Nemirovskaya T. Paradoxical effect of IKKβ inhibition on the expression of E3 ubiquitin ligases and unloading-induced skeletal muscle atrophy. Physiol Rep. 2017;5: pubmed publisher
    ..Our study for the first time showed that inhibiting IKKβ in vivo during 3-day unloading failed to diminish expression of ubiquitin ligases and prevent muscle atrophy. ..
  89. Wu X, Qi X, Qu B, Zhang Z, Liang M, Li C, et al. Evasion of antiviral immunity through sequestering of TBK1/IKK?/IRF3 into viral inclusion bodies. J Virol. 2014;88:3067-76 pubmed publisher
    ..Sequestration of the IKK complex and active IRF3 into viral IBs through the interaction of NSs and TBK1 is a novel mechanism for viral evasion of innate immunity. ..
  90. Koido K, Eller T, Kingo K, Koks S, Traks T, Shlik J, et al. Interleukin 10 family gene polymorphisms are not associated with major depressive disorder and panic disorder phenotypes. J Psychiatr Res. 2010;44:275-7 pubmed publisher
    ..Significant associations were detected for SNP rs1539243 in IKBKE (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon) gene showing different allelic and ..