Prokaryotic ubiquitin-like protein (Pup), proteasomes and pathogenesis

Abstract

Tagging eukaryotic proteins with ubiquitin can target them for proteasomal degradation. However, despite the presence of proteasomes in several bacterial and all archaeal species, prokaryotic homologues of ubiquitin were presumed to be absent. In this Progress article, Heran Darwin describes the characterization of a prokaryotic ubiquitin-like protein (Pup) that is covalently attached to proteins, resulting in their proteasome-mediated degradation. Proteasomes are ATP-dependent, multisubunit proteases that are found in all eukaryotes and archaea and some bacteria. In eukaryotes, the small protein ubiquitin is covalently attached in a post-translational manner to proteins that are targeted for proteasomal degradation. Despite the presence of proteasomes in many prokaryotes, ubiquitin or other post-translational protein modifiers were presumed to be absent from these organisms. Recently a prokaryotic ubiquitin-like protein, Pup, was found to target proteins for proteolysis by the Mycobacterium tuberculosis proteasome. The discovery of this ubiquitin-like modifier opens up the possibility that other bacteria may also have small post-translational protein tagging systems, with the ability to affect cellular processes.