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Ubiquitin Conjugation and Deconjugation in NF-κB Signaling

  • Chapter
Conjugation and Deconjugation of Ubiquitin Family Modifiers

Part of the book series: Subcellular Biochemistry ((SCBI,volume 54))

Abstract

Transcription factor NF-κB regulates the physiological response to a variety of stimuli. The NF-κB pathway has served as a paradigm for analyzing the impact of the covalent protein modifier ubiquitin on signal transduction. The discovery in the early 1990s that degradation of cytosolic NF-κB inhibitors (IκBs) is mediated by the ubiquitin proteasome system (UPS) was the first example for a direct involvement of ubiquitination in cellular signaling. By now it has become clear that the role of the ubiquitin system in the NF-κB pathway extends far beyond triggering IκB destruction. The IκB kinase (IKK) complex is the key regulator of NF-κB. Attachment of ubiquitin chains to the IKK complex and to further upstream components drives NF-κB signaling pathways by promoting the clustering of the signaling network. Whereas ubiquitin conjugation serves a positive function in the NF-κB pathway, ubiquitin deconjugation acts as a negative regulatory feedback mechanism that is critically involved in balancing the strength and the duration of the NF-κB response. Moreover, inactivation of deconjugating enzymes can cause sustained NF-κB activity under pathological conditions like chronic inflammation or cancer. Here we review the impact of the ubiquitin system on the NF-κB signaling network by putting a focus on the enzymes that help to shape the plasticity of the NF-κB response.

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Authors and Affiliations

  1. Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Toxicology, Department Cellular Signal Integration, Ingolstädter Landstrasse. 1, 85764, Neuherberg, Germany

    Michael Düwel, Kamyar Hadian & Daniel Krappmann

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  1. Michael Düwel
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  2. Kamyar Hadian
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  3. Daniel Krappmann
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Correspondence to Daniel Krappmann .

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  1. Department of Biology, Division of Immunology, University of Konstanz, Konstanz, Germany

    Marcus Groettrup PhD

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Düwel, M., Hadian, K., Krappmann, D. (2010). Ubiquitin Conjugation and Deconjugation in NF-κB Signaling. In: Groettrup, M. (eds) Conjugation and Deconjugation of Ubiquitin Family Modifiers. Subcellular Biochemistry, vol 54. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6676-6_7

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