Ubiquitination and degradation of the inhibitors of NF-kappaB.

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