Figure 8. Model for UBA-mediated protection from proteasomal degradation.

(a) The schematic drawing shows an ubiquitin receptor (Rad23/Dsk2) that delivers a ubiquitylated substrate to the 26S proteasome. The ubiquitin receptor binds the proteasome through its N-terminal UbL domain that directly interacts with the Rpn1 subunit of the proteasome, thereby delivering the polyubiquitylated substrate bound to the UBA domain. Wild-type Rad23/Dsk2 contains a C-terminal UBA domain that resists initiation of protein degradation, resulting in release of the ubiquitin receptor from the proteasome. (b) In case the ubiquitin receptor has a mutant UBA domain or is provided with a polypeptide that can function as an unstructured initiation site, the ubiquitin receptor itself is translocated into the proteasome and hydrolyzed in the proteolytic chamber.