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A pervasive role of ubiquitin conjugation in activation and termination of IkappaB kinase pathways

Item Type:Review
Title:A pervasive role of ubiquitin conjugation in activation and termination of IkappaB kinase pathways
Creators Name:Krappmann, D. and Scheidereit, C.
Abstract:The nuclear factor (NF)-κB pathway is a paradigm for gene expression control by ubiquitin-mediated protein degradation. In stimulated cells, phosphorylation by the IκB kinase (IKK) complex primes NF-κB-inhibiting IκB molecules for lysine (Lys)-48-linked polyubiquitination and subsequent destruction by the 26S proteasome. However, recent studies indicate that the ubiquitin (Ub) system controls NF-κB pathways at many levels. Ub ligases are activated by different upstream signalling pathways, and they function as central regulators of IKK and c-Jun amino-terminal kinase activation. The assembly of Lys 63 polyUb chains provides docking surfaces for the recruitment of IKK-activating complexes, a reaction that is counteracted by deubiquitinating enzymes. Furthermore, Ub conjugation targets upstream signalling mediators as well as nuclear NF-κB for post-inductive degradation to limit the duration of signalling.
Keywords:Cancer, Development, Differentiation, Immunity, Inflammation
Source:EMBO Reports
ISSN:1469-221X
Publisher:Nature Publishing Group (U.K.)
Volume:6
Number:4
Page Range:321-326
Date:1 January 2005
Official Publication:https://doi.org/10.1038/sj.embor.7400380
PubMed:View item in PubMed

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