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Ikbke  -  inhibitor of kappaB kinase epsilon

Mus musculus

Synonyms: AW558201, I-kappa-B kinase epsilon, IKK-E, IKK-epsilon, IKK-i, ...
 
 
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Disease relevance of Ikbke

 

High impact information on Ikbke

  • Furthermore, the IFN response in TBK1(-/-) embryonic fibroblasts can be restored by reconstitution with wild-type IKK-i but not a mutant IKK-i lacking kinase activity [4].
  • Here, we show that purified recombinant IKK-epsilon and TBK1 directly phosphorylate the critical serine residues in IRF3 [5].
  • Kinase assay confirmed that IKKepsilon was activated in RA synovium, and immunostaining showed localization of pIKKepsilon to the intimal lining [6].
  • Antiviral gene expression in rheumatoid arthritis: role of IKKepsilon and interferon regulatory factor 3 [6].
  • Because NF-kappaB activation is similar in wild-type and IKKepsilon knockout murine FLS, studies were performed to identify an alternative substrate for IKKepsilon [1].
 

Biological context of Ikbke

  • Functional studies in cultured FLS showed that IKKepsilon kinase activity is rapidly induced by cytokines, although IkappaB phosphorylation is significantly less compared with IKK2 [1].
  • Antiviral gene expression was also reduced in FLS from IKKepsilon(-/-) mice compared with IKKepsilon(+/+) mice [6].
  • Disruption of the NF-kappaB pathway results in the blockade of the inducible up-regulation of C/EBPbeta, C/EBPdelta, and IKKi genes [7].
  • Subsequently, overexpression of IKKepsilon resulted in 80% inhibition of both the positive and negative replicative strands of the HCV replicon [3].
 

Anatomical context of Ikbke

  • Using the suppression subtractive hybridization technique, we isolated a novel kinase, IKK-i, whose message is drastically induced by lipopolysaccharide (LPS) in the mouse macrophage cell line RAW264 [8].
 

Associations of Ikbke with chemical compounds

  • We report that the product of the inducible gene encoding the kinase known as IKKi/IKKepsilon (IKKi) is required for expression of a group of genes up-regulated by pro-inflammatory stimuli such as bacterial endotoxin (lipopolysaccharide (LPS)) [7].
  • Recent studies demonstrated that serine/threonine kinases IKK-i/TBK1 are critical for the regulation of IFN-beta as well as IFN-inducible genes [9].
 

Analytical, diagnostic and therapeutic context of Ikbke

  • Dominant-negative (DN) IKKepsilon adenoviral infection of human fibroblast-like synoviocytes (FLS) was followed by poly(I-C) stimulation and Western blotting [6].

References

  1. Regulation of c-Jun phosphorylation by the I kappa B kinase-epsilon complex in fibroblast-like synoviocytes. Sweeney, S.E., Hammaker, D., Boyle, D.L., Firestein, G.S. J. Immunol. (2005) [Pubmed]
  2. Inducible IkappaB kinase/IkappaB kinase epsilon expression is induced by CK2 and promotes aberrant nuclear factor-kappaB activation in breast cancer cells. Eddy, S.F., Guo, S., Demicco, E.G., Romieu-Mourez, R., Landesman-Bollag, E., Seldin, D.C., Sonenshein, G.E. Cancer Res. (2005) [Pubmed]
  3. Inhibition of RIG-I-dependent signaling to the interferon pathway during hepatitis C virus expression and restoration of signaling by IKKepsilon. Breiman, A., Grandvaux, N., Lin, R., Ottone, C., Akira, S., Yoneyama, M., Fujita, T., Hiscott, J., Meurs, E.F. J. Virol. (2005) [Pubmed]
  4. Differential requirement for TANK-binding kinase-1 in type I interferon responses to toll-like receptor activation and viral infection. Perry, A.K., Chow, E.K., Goodnough, J.B., Yeh, W.C., Cheng, G. J. Exp. Med. (2004) [Pubmed]
  5. IFN-regulatory factor 3-dependent gene expression is defective in Tbk1-deficient mouse embryonic fibroblasts. McWhirter, S.M., Fitzgerald, K.A., Rosains, J., Rowe, D.C., Golenbock, D.T., Maniatis, T. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  6. Antiviral gene expression in rheumatoid arthritis: role of IKKepsilon and interferon regulatory factor 3. Sweeney, S.E., Mo, L., Firestein, G.S. Arthritis Rheum. (2007) [Pubmed]
  7. IKKi/IKKepsilon plays a key role in integrating signals induced by pro-inflammatory stimuli. Kravchenko, V.V., Mathison, J.C., Schwamborn, K., Mercurio, F., Ulevitch, R.J. J. Biol. Chem. (2003) [Pubmed]
  8. IKK-i, a novel lipopolysaccharide-inducible kinase that is related to IkappaB kinases. Shimada, T., Kawai, T., Takeda, K., Matsumoto, M., Inoue, J., Tatsumi, Y., Kanamaru, A., Akira, S. Int. Immunol. (1999) [Pubmed]
  9. Interferon response induced by Toll-like receptor signaling. Takeuchi, O., Hemmi, H., Akira, S. J. Endotoxin Res. (2004) [Pubmed]
 
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