Fig. 1. Comparison of the ubiquitin and Pup proteasome pathways.

(a) Ubiquitin is adenylated at the C-terminal di-glycine, followed by a series of thioesterification reactions and finally conjugated to a doomed protein. In general, multiple ubiquitin molecules are conjugated to the protein and/or ubiquitin itself. Ubiquitin is removed by DUBs and the doomed protein is unfolded and delivered into the 20S CP by the RP. (b) Pup is first deamidated at the C-terminal glutamine and then conjugated to doomed proteins (conjugation shown at the γ-COOH for simplicity). Pup targets proteins to Mpa and the proteasome, however, it is unknown whether Pup is recycled and whether additional proteins are needed to complete the process.