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. Sweeney S, Hammaker D, Boyle D, Firestein G. Regulation of c-Jun phosphorylation by the I kappa B kinase-epsilon complex in fibroblast-like synoviocytes. J Immunol. 2005;174:6424-30 pubmed
    ..The IkappaB kinase (IKK)-related kinase, IKKepsilon/IKKi, which plays a pivotal role in regulating antiviral gene transcription, is constitutively expressed by cultured ..
  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. 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...
  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. 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. ..

More Information

Publications130 found, 100 shown here

  1. 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...
  2. 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. ..
  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. 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. ..
  5. 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...
  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. 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. ..
  11. 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. ..
  12. 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. ..
  13. 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...
  14. 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. ..
  15. 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.
  16. 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'-..
  17. 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. ..
  18. 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. ..
  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. Wietek C, Cleaver C, Ludbrook V, Wilde J, White J, Bell D, et al. IkappaB kinase epsilon interacts with p52 and promotes transactivation via p65. J Biol Chem. 2006;281:34973-81 pubmed
    ..These novel interactions reveal a hitherto unknown function of IKKepsilon in the regulation of the alternative NF-kappaB activation pathway involving p52 and p65. ..
  21. Pythoud C, Rodrigo W, Pasqual G, Rothenberger S, Martinez Sobrido L, de la Torre J, et al. Arenavirus nucleoprotein targets interferon regulatory factor-activating kinase IKK?. J Virol. 2012;86:7728-38 pubmed publisher
    ..LCMV NP bound the kinase domain (KD) of IKK? (IKBKE) and blocked its autocatalytic activity and its ability to phosphorylate IRF3, without undergoing phosphorylation...
  22. Wu S, Teng M, Er L, Hsiao W, Hsu L, Yeh C, et al. Association between NF-?B Pathway Gene Variants and sICAM1 Levels in Taiwanese. PLoS ONE. 2017;12:e0169516 pubmed publisher
    ..three SNPs in the ICAM1 gene and eight SNPs in six of the NF-?B pathway genes (NFKB1, PDCD11, TNFAIP3, NKAPL, IKBKE, and PRKCB) were analyzed for their association with sICAM1 levels in 480 individuals...
  23. Paz S, Sun Q, Nakhaei P, Romieu Mourez R, Goubau D, Julkunen I, et al. Induction of IRF-3 and IRF-7 phosphorylation following activation of the RIG-I pathway. Cell Mol Biol (Noisy-le-grand). 2006;52:17-28 pubmed
    ..These studies link RIG-I sensing of viral RNA to downstream kinase signaling and phosphorylation of IRF-3 and IRF-7 via the MAVS/IPS/VISA/Cardif adaptor. ..
  24. Liu D, Sheng C, Gao S, Yao C, Li J, Jiang W, et al. SOCS3 Drives Proteasomal Degradation of TBK1 and Negatively Regulates Antiviral Innate Immunity. Mol Cell Biol. 2015;35:2400-13 pubmed publisher
  25. Grøndahl J, Fossdal Ø, Hauge Iversen T, Husebye E, Rosvold E, Kongshavn T. Admissions to the medical department - who admits and why. Tidsskr Nor Laegeforen. 2018;138: pubmed publisher
    ..Andelen innleggelser fra fastlege var høyere enn i tilsvarende studier. Én av 15 innleggelser (7 %) ble vurdert som aktuell for alternativ. Triagering skiller ikke ut pasientforløp som er egnet for alternativ til innleggelse.
  26. Tollånes M, Knudsen A, Vollset S, Kinge J, Skirbekk V, Øverland S. Disease burden in Norway in 2016. Tidsskr Nor Laegeforen. 2018;138: pubmed publisher
    ..hatt god oversikt over dødsårsaker, men vi vet mindre om byrden fra tilstander som medfører sykelighet, såkalt ikke-dødelig helsetap...
  27. Civas A, Genin P, Morin P, Lin R, Hiscott J. Promoter organization of the interferon-A genes differentially affects virus-induced expression and responsiveness to TBK1 and IKKepsilon. J Biol Chem. 2006;281:4856-66 pubmed
  28. Rajsbaum R, Versteeg G, Schmid S, Maestre A, Belicha Villanueva A, Martínez Romero C, et al. Unanchored K48-linked polyubiquitin synthesized by the E3-ubiquitin ligase TRIM6 stimulates the interferon-IKK? kinase-mediated antiviral response. Immunity. 2014;40:880-95 pubmed publisher
    ..Our work attributes a previously unrecognized activating role of K48-linked unanchored polyubiquitin chains in kinase activation and identifies the UbE2K-TRIM6-ubiquitin axis as critical for IFN signaling and antiviral response. ..
  29. Wu J, Zhao F, Fan K, Zhang J, Xu B, Wang Q, et al. Dihydromyricetin Inhibits Inflammation of Fibroblast-Like Synoviocytes through Regulation of Nuclear Factor-κB Signaling in Rats with Collagen-Induced Arthritis. J Pharmacol Exp Ther. 2019;368:218-228 pubmed publisher
  30. Yuan Y, Wang J, Chen Q, Wu Q, Deng W, Zhou H, et al. Long non-coding RNA cytoskeleton regulator RNA (CYTOR) modulates pathological cardiac hypertrophy through miR-155-mediated IKKi signaling. Biochim Biophys Acta Mol Basis Dis. 2019;: pubmed publisher
    ..16 and was positively correlated with IKBKE according to the data from The GTEx project...
  31. Guo J, Tian W, Shu S, Xin Y, Shou C, Cheng J. IKBKE phosphorylation and inhibition of FOXO3a: a mechanism of IKBKE oncogenic function. PLoS ONE. 2013;8:e63636 pubmed publisher
    ..Here we report that IKBKE regulates FOXO3a through phosphorylation of FOXO3a-Ser644...
  32. Wei B, Cui Y, Huang Y, Liu H, Li L, Li M, et al. Tom70 mediates Sendai virus-induced apoptosis on mitochondria. J Virol. 2015;89:3804-18 pubmed publisher
    ..Interestingly, IKK-i plays an essential role in this activation. This study uncovers a novel mechanism of SeV-induced apoptosis. ..
  33. Renner F, Saul V, Pagenstecher A, Wittwer T, Schmitz M. Inducible SUMO modification of TANK alleviates its repression of TLR7 signalling. EMBO Rep. 2011;12:129-35 pubmed publisher
    ..Reconstitution experiments show that an absence of TANK SUMOylation impairs inducible expression of distinct TLR7-dependent target genes, providing a molecular mechanism that allows the control of TANK function. ..
  34. Abeyrathna P, Su Y. The critical role of Akt in cardiovascular function. Vascul Pharmacol. 2015;74:38-48 pubmed publisher
    ..The serine site is phosphorylated by mTORC2. Ack1, Src, PTK6, TBK1, IKBKE and IKKε are some of the non-canonical pathways which affect the Akt activity...
  35. Liang J, Wu J, Liu Y, Zhang Z, Wu Q, Chen H, et al. Patchoulene Epoxide Isolated from Patchouli Oil Suppresses Acute Inflammation through Inhibition of NF-?B and Downregulation of COX-2/iNOS. Mediators Inflamm. 2017;2017:1089028 pubmed publisher
    ..In conclusion, PAO exhibited potent anti-inflammatory activity probably by suppressing the activation of iNOS, COX-2 and NF-?B signaling pathways. ..
  36. Xu G, Lo Y, Li Q, Napolitano G, Wu X, Jiang X, et al. Crystal structure of inhibitor of κB kinase β. Nature. 2011;472:325-30 pubmed publisher
    ..Other IKK family members, IKKα, TBK1 and IKK-i, may have a similar trimodular architecture and function. ..
  37. Masatani T, Ozawa M, Yamada K, Ito N, Horie M, Matsuu A, et al. Contribution of the interaction between the rabies virus P protein and I-kappa B kinase ϵ to the inhibition of type I IFN induction signalling. J Gen Virol. 2016;97:316-26 pubmed publisher
    ..These findings suggest that the P protein of RABV street strains may contribute to efficient evasion of host innate immunity. ..
  38. Zhang L, Chen W, Xu Y, Wang L, Iskandar R, Wang Y, et al. The expression of inhibitor of nuclear factor kappa-B kinase epsilon (IKKe) in human aortic aneurysm. Folia Morphol (Warsz). 2017;76:372-378 pubmed publisher
    ..In this study we will explore the expression of inhibitor of nuclear factor kappa-B kinase epsilon (IKKe) in AA and its potential underlying molecular mechanism in AA...
  39. Pedro de Magalhães J, Thompson L, de Lima I, Gaskill D, Li X, Thornton D, et al. A Reassessment of Genes Modulating Aging in Mice Using Demographic Measurements of the Rate of Aging. Genetics. 2018;208:1617-1630 pubmed publisher
  40. Ikeda F, Hecker C, Rozenknop A, Nordmeier R, Rogov V, Hofmann K, et al. Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes. EMBO J. 2007;26:3451-62 pubmed
    ..We propose that the ULD is a regulatory component of the TBK1/IKK-i kinases involved in the control of the kinase activation, substrate presentation and downstream signaling pathways. ..
  41. Sandling J, Garnier S, Sigurdsson S, Wang C, Nordmark G, Gunnarsson I, et al. A candidate gene study of the type I interferon pathway implicates IKBKE and IL8 as risk loci for SLE. Eur J Hum Genet. 2011;19:479-84 pubmed publisher
    ..01 in the initial screen were then followed up in 344 additional Swedish patients and 1299 controls. SNPs in the IKBKE, TANK, STAT1, IL8 and TRAF6 genes gave nominal signals of association with SLE in this extended Swedish cohort...
  42. Barbie T, Alexe G, Aref A, Li S, Zhu Z, Zhang X, et al. Targeting an IKBKE cytokine network impairs triple-negative breast cancer growth. J Clin Invest. 2014;124:5411-23 pubmed publisher
    ..Here, we found that inducible IκB kinase-related (IKK-related) kinase IKBKE expression and JAK/STAT pathway activation compose a cytokine signaling network in the immune-activated subset of ..
  43. Bharaj P, Wang Y, Dawes B, Yun T, Park A, Yen B, et al. The Matrix Protein of Nipah Virus Targets the E3-Ubiquitin Ligase TRIM6 to Inhibit the IKK? Kinase-Mediated Type-I IFN Antiviral Response. PLoS Pathog. 2016;12:e1005880 pubmed publisher
    ..These findings expand the universe of viral IFN antagonism strategies and provide a new potential target for development of therapeutic interventions against NiV infections. ..
  44. Ma C, Lv Q, Teng S, Yu Y, Niu K, Yi C. Identifying key genes in rheumatoid arthritis by weighted gene co-expression network analysis. Int J Rheum Dis. 2017;20:971-979 pubmed publisher
    ..were enriched in totally enriched in 17 Gene Ontology terms, mainly related to immune response (CD97, FYB, CXCL1, IKBKE, CCR1, etc.), inflammatory response (CD97, CXCL1, C3AR1, CCR1, LYZ, etc...
  45. Zhang Z, Wang Z, Huang K, Liu Y, Wei C, Zhou J, et al. PLK4 is a determinant of temozolomide sensitivity through phosphorylation of IKBKE in glioblastoma. Cancer Lett. 2018;443:91-107 pubmed publisher
    ..Here, we show that PLK4 affects TMZ sensitivity by regulating the IKBKE/NF-κB axis...
  46. Ganesan S, Volodina O, Pearce S, Gabler N, Baumgard L, Rhoads R, et al. Acute heat stress activated inflammatory signaling in porcine oxidative skeletal muscle. Physiol Rep. 2017;5: pubmed publisher
    ..These data indicate that heat stress activated inflammatory signaling in the porcine STR muscle via the AP-1 pathway and early activation of the NF-κB pathway. ..
  47. Beyett T, Gan X, Reilly S, Chang L, Gomez A, Saltiel A, et al. Carboxylic Acid Derivatives of Amlexanox Display Enhanced Potency toward TBK1 and IKKε and Reveal Mechanisms for Selective Inhibition. Mol Pharmacol. 2018;94:1210-1219 pubmed publisher
    ..The structure-activity relationships and cocrystal structures described herein will aid in future structure-guided inhibitor development using the amlexanox pharmacophore for the treatment of obesity and type 2 diabetes. ..
  48. Useche Y, Ribeiro Alves M, Restrepo B, Salgado D, Narváez C, Campo O, et al. Single-Nucleotide Polymorphisms in NOD1, RIPK2, MICB, PLCE1, TNF, and IKBKE Genes Associated with Symptomatic Dengue in Children from Colombia. Viral Immunol. 2018;31:613-623 pubmed publisher
    ..Conversely, we found one SNP in TNF gene and two haplotypes in the IKBKE gene associated with resistance to develop dengue...
  49. 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
  50. 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...
  51. 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 ..
  52. 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. ..
  53. 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. ..
  54. 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. ..
  55. 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...
  56. 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. ..
  57. 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...
  58. 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...
  59. 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. ..
  60. 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. ..
  61. 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...
  62. 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 ..
  63. 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...
  64. 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...
  65. 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...
  66. 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. ..
  67. 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 ..
  68. 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. ..
  69. 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 IKKε family kinase, as another critical regulator of allophagy...
  70. 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 ..
  71. 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. ..
  72. 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. ..
  73. 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. ..
  74. 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. ..
  75. 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...
  76. 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. ..
  77. 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. ..
  78. 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. ..
  79. 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...
  80. 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. ..
  81. 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...
  82. 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...
  83. 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. ..
  84. 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...
  85. 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...
  86. 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 ..
  87. 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. ..
  88. 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. ..
  89. 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. ..
  90. 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. ..
  91. 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 ..