PUPylation: something old, something new, something borrowed, something Glu

Most eukaryotic proteins are degraded by the 26S proteasome as a consequence of their covalent modification with ubiquitin. Although the proteasome is found in some prokaryotes, ubiquitin is not, which indicates that substrates are targeted to prokaryotic proteasomes by a fundamentally different mechanism. A recent study has identified Pup (prokaryotic ubiquitin-like protein) as a mycobacterial protein that functions in a manner analogous to ubiquitin for proteasome-dependent proteolysis in prokaryotes.