Pupylation versus ubiquitylation: tagging for proteasome-dependent degradation

Abstract

Prokaryotic ubiquitin-like protein (Pup) is the first identified prokaryotic protein that is functionally analogous to ubiquitin. Despite using the proteasome as the end-point for proteolysis, Pup differs from ubiquitin both biochemically and structurally. We will discuss these differences that have been highlighted by several recent studies. Finally, we will speculate on the possible interactions between the two analogous pathways in pathogen and host.

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.