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Inhibitor of KappaB

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Synonyms

ANK, ankyrin; ELAM1, endothelial-leukocyte adhesion molecule 1; IκB, inhibitor of kappaB; LPS, lipopolysaccharide; MALT, molecule possessing ankyrin repeats induced by lipopolysaccharide; NF-κB, nuclear factor kappaB

Historical Background

The transcriptional factor NF-κB – a key regulator of cellular events such as cell growth, immune response, and cell survival – was first identified by Dr. David Baltimore’s group (Sen and Baltimore 1986). Inhibitor of kappaB (IκB) can form a complex with NF-κB and control these events. IκB family proteins harbor an ankyrin (ANK) repeat domain, a core motif of NF-κB binding, which was first identified in the cell-cycle gene sequences of yeast and Drosophila in 1987 (Breeden and Nasmyth 1987). IκB family members have been found to have conserved ANK repeat domains, including β-strand and α-helix repeat sequences. On the basis of extensive studies, nine IκB family proteins harboring ANK repeats have been identified, and these IκB proteins are...

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References

  • Baeuerle PA, Baltimore D. I kappa B: a specific inhibitor of the NF-kappa B transcription factor. Science. 1988;242:540–6.

    Article  CAS  PubMed  Google Scholar 

  • Beg AA, Sha WC, Bronson RT, Baltimore D. Constitutive NF-kappa B activation, enhanced granulopoiesis, and neonatal lethality in I kappa B alpha-deficient mice. Genes Dev. 1995;9:2736–46.

    Article  CAS  PubMed  Google Scholar 

  • Breeden L, Nasmyth K. Similarity between cell-cycle genes of budding yeast and fission yeast and the Notch gene of Drosophila. Nature. 1987;329:651–4. doi:10.1038/329651a0.

    Article  CAS  PubMed  Google Scholar 

  • Ferreiro DU, Komives EA. Molecular mechanisms of system control of NF-kappaB signaling by IkappaBalpha. Biochemistry. 2010;49:1560–7. doi:10.1021/bi901948j.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fiorini E, Schmitz I, Marissen WE, Osborn SL, Touma M, Sasada T, et al. Peptide-induced negative selection of thymocytes activates transcription of an NF-kappa B inhibitor. Mol Cell. 2002;9:637–48.

    Article  CAS  PubMed  Google Scholar 

  • Franzoso G, Bours V, Azarenko V, Park S, Tomita-Yamaguchi M, Kanno T, et al. The oncoprotein Bcl-3 can facilitate NF-kappa B-mediated transactivation by removing inhibiting p50 homodimers from select kappa B sites. EMBO J. 1993;12:3893–901.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Franzoso G, Carlson L, Scharton-Kersten T, Shores EW, Epstein S, Grinberg A, et al. Critical roles for the Bcl-3 oncoprotein in T cell-mediated immunity, splenic microarchitecture, and germinal center reactions. Immunity. 1997;6:479–90.

    Article  CAS  PubMed  Google Scholar 

  • Hayden MS, Ghosh S. Shared principles in NF-kappaB signaling. Cell. 2008;132:344–62. doi:10.1016/j.cell.2008.01.020.

    Article  CAS  PubMed  Google Scholar 

  • Huxford T, Huang DB, Malek S, Ghosh G. The crystal structure of the IkappaBalpha/NF-kappaB complex reveals mechanisms of NF-kappaB inactivation. Cell. 1998;95:759–70.

    Article  CAS  PubMed  Google Scholar 

  • Jackman RW, Wu CL, Kandarian SC. The ChIP-seq-defined networks of Bcl-3 gene binding support its required role in skeletal muscle atrophy. PLoS One. 2012;7:e51478. doi:10.1371/journal.pone.0051478.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kitamura H, Kanehira K, Okita K, Morimatsu M, Saito M. MAIL: a novel nuclear I kappa B protein that potentiates LPS-induced IL-6 production. FEBS Lett. 2000;485:53–6.

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi S, Hara A, Isagawa T, Manabe I, Takeda K, MaruYama T. The nuclear IkappaB family protein IkappaBNS influences the susceptibility to experimental autoimmune encephalomyelitis in a murine model. PLoS One. 2014;9:e110838. doi:10.1371/journal.pone.0110838.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kuwata H, Watanabe Y, Miyoshi H, Yamamoto M, Kaisho T, Takeda K, et al. IL-10-inducible Bcl-3 negatively regulates LPS-induced TNF-alpha production in macrophages. Blood. 2003;102:4123–9. doi:10.1182/blood-2003-04-1228.

    Article  CAS  PubMed  Google Scholar 

  • Massoumi R, Chmielarska K, Hennecke K, Pfeifer A, Fassler R. Cyld inhibits tumor cell proliferation by blocking Bcl-3-dependent NF-kappaB signaling. Cell. 2006;125:665–77. doi:10.1016/j.cell.2006.03.041.

    Article  CAS  PubMed  Google Scholar 

  • Ohno H, Takimoto G, McKeithan TW. The candidate proto-oncogene bcl-3 is related to genes implicated in cell lineage determination and cell cycle control. Cell. 1990;60:991–7.

    Article  CAS  PubMed  Google Scholar 

  • Okuma A, Hoshino K, Ohba T, Fukushi S, Aiba S, Akira S, et al. Enhanced apoptosis by disruption of the STAT3-IkappaB-zeta signaling pathway in epithelial cells induces Sjogren’s syndrome-like autoimmune disease. Immunity. 2013;38:450–60. doi:10.1016/j.immuni.2012.11.016.

    Article  CAS  PubMed  Google Scholar 

  • Sen R, Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell. 1986;46:705–16.

    Article  CAS  PubMed  Google Scholar 

  • Thompson JE, Phillips RJ, Erdjument-Bromage H, Tempst P, Ghosh S. I kappa B-beta regulates the persistent response in a biphasic activation of NF-kappa B. Cell. 1995;80:573–82.

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto M, Yamazaki S, Uematsu S, Sato S, Hemmi H, Hoshino K, et al. Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IkappaBzeta. Nature. 2004;430:218–22. doi:10.1038/nature02738.

    Article  CAS  PubMed  Google Scholar 

  • Zabel U, Baeuerle PA. Purified human I kappa B can rapidly dissociate the complex of the NF-kappa B transcription factor with its cognate DNA. Cell. 1990;61:255–65.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Takashi MaruYama .

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MaruYama, T. (2016). Inhibitor of KappaB. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_101651-1

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  • DOI: https://doi.org/10.1007/978-1-4614-6438-9_101651-1

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  • Publisher Name: Springer, New York, NY

  • Online ISBN: 978-1-4614-6438-9

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