title: Ubiquitin Conjugation and Deconjugation in NF-κB Signaling.
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.
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Toxicology, Department Cellular Signal Integration, Ingolstädter Landstrasse. 1, 85764, Neuherberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Düwel
authors.forename: Kamyar
authors.initials: K
authors.lastname: Hadian
authors.forename: Daniel
authors.initials: D
authors.lastname: Krappmann
mesh_terms: D006801:Humans; D051550:I-kappa B Kinase; D016328:NF-kappa B; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D016328:NF-kappa B; D025801:Ubiquitin; D051550:I-kappa B Kinase