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

D Krappmann, C Scheidereit - EMBO reports, 2005 - embopress.org
EMBO reports, 2005embopress.org
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 …
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.
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