Recognition of Client Proteins by the Proteasome.

The ubiquitin proteasome system controls the concentrations of regulatory proteins and removes damaged and misfolded proteins from cells. Proteins are targeted to the protease at the center of this system, the proteasome, by ubiquitin tags, but ubiquitin is also used as a signal in other cellular processes. Specificity is conferred by the size and structure of the ubiquitin tags, which are recognized by receptors associated with the different cellular processes. However, the ubiquitin code remains ambiguous, and the same ubiquitin tag can target different proteins to different fates. After binding substrate protein at the ubiquitin tag, the proteasome initiates degradation at a disordered region in the substrate. The proteasome has pronounced preferences for the initiation site, and its recognition represents a second component of the degradation signal.