Ubiquitination and Degradation of the Inhibitors of NF-κB

The key step in NF-kappa B activation is the release of the NF-kappa B dimers from their inhibitory proteins, achieved via proteolysis of the I kappa Bs. This irreversible signaling step constitutes a commitment to transcriptional activation. The signal is eventually terminated through nuclear expulsion of NF-kappa B, the outcome of a negative feedback loop based on I kappa B alpha transcription, synthesis, and I kappa B alpha-dependent nuclear export of NF-kappa B (Karin and Ben-Neriah 2000). Here, we review the process of signal-induced I kappa B ubiquitination and degradation by comparing the degradation of several I kappa Bs and discussing the characteristics of I kappa Bs' ubiquitin machinery.