Ubiquitination and Degradation of the Inhibitors of NF-κB

• Published in: Cold Spring Harbor perspectives in biology 2010-02, Vol.2 (2)
• Main Authors: Kanarek, Naama, London, Nir, Schueler-Furman, Ora, Ben-Neriah, Yinon
• Format: Article
• Language: English
• ISSN: 1943-0264
• DOI: 10.1101/cshperspect.a000166

The key step in NF-κB activation is the release of the NF-κB dimers from their inhibitory proteins, achieved via proteolysis of the IκBs. This irreversible signaling step constitutes a commitment to transcriptional activation. The signal is eventually terminated through nuclear expulsion of NF-κB, the outcome of a negative feedback loop based on IκBα transcription, synthesis, and IκBα-dependent nuclear export of NF-κB (Karin and Ben-Neriah 2000). Here, we review the process of signal-induced IκB ubiquitination and degradation by comparing the degradation of several IκBs and discussing the characteristics of IκBs’ ubiquitin machinery. Ubiquitin-dependent degradation of IκB activates NF-κB. A single E3 ubiquitin ligase, β-TrCP, targets several IκB proteins for degradation.