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...
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Baeuerle PA, Baltimore D. I kappa B: a specific inhibitor of the NF-kappa B transcription factor. Science. 1988;242:540–6.
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.
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. https://doi.org/10.1038/329651a0.
Ferreiro DU, Komives EA. Molecular mechanisms of system control of NF-kappaB signaling by IkappaBalpha. Biochemistry. 2010;49:1560–7. https://doi.org/10.1021/bi901948j.
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.
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.
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.
Hayden MS, Ghosh S. Shared principles in NF-kappaB signaling. Cell. 2008;132:344–62. https://doi.org/10.1016/j.cell.2008.01.020.
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.
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. https://doi.org/10.1371/journal.pone.0051478.
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.
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. https://doi.org/10.1371/journal.pone.0110838.
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. https://doi.org/10.1182/blood-2003-04-1228.
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. https://doi.org/10.1016/j.cell.2006.03.041.
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.
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. https://doi.org/10.1016/j.immuni.2012.11.016.
Sen R, Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell. 1986;46:705–16.
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.
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. https://doi.org/10.1038/nature02738.
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.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this entry
Cite this entry
MaruYama, T. (2018). Inhibitor of KappaB. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101651
Download citation
DOI: https://doi.org/10.1007/978-3-319-67199-4_101651
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-67198-7
Online ISBN: 978-3-319-67199-4
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences