Bacterial usurpation of the OTU deubiquitinase fold

Abstract

The extensive cellular signalling events controlled by posttranslational ubiquitination are tightly regulated through the action of specialized proteases termed deubiquitinases. Among them, the OTU family of deubiquitinases can play very specialized roles in the regulation of discrete subtypes of ubiquitin signals that control specific cellular functions. To exert control over host cellular functions, some pathogenic bacteria have usurped the OTU deubiquitinase fold as a secreted virulence factor that interferes with ubiquitination inside infected cells. Herein, we provide a review of the function of bacterial OTU deubiquitinases during infection, the structural basis for their deubiquitinase activities and the bioinformatic approaches leading to their identification. Understanding bacterial OTU deubiquitinases holds the potential for discoveries not only in bacterial pathogenesis but in eukaryotic biology as well.

Ubiquitin‐targeted bacterial effectors: rule breakers of the ubiquitin system

“…A family of related Legionella OTU (LOT) DUBs has recently been identified by sequence homology (Pruneda et al , 2023). The first example, LotA (lpg2248), contains two active OTU‐like domains, the first of which is capable of hydrolyzing K6‐linked polyUb, while the second appears to prefer longer K48‐linked and K63‐linked polyUb chains (Kubori et al , 2018; Luo et al , 2022; Takekawa et al , 2022; Kang et al , 2023; Warren et al , 2023).…”

Targeting the Ubiquitin–Proteasome System and Recent Advances in Cancer Therapy

“…Similarly, deubiquitinases modulate diverse cellular events, including the cell cycle [ 25 ], apoptosis [ 26 ], receptor signaling [ 16 , 21 ], gene transcription [ 24 ] and DNA repair pathways [ 23 ]. The ubiquitination system is also conserved throughout evolution and modulates a wide range of biological functions in bacteria and viruses, where it is emerging as a major player in the bacterial pathogenic mechanisms of infectious diseases [ 27 , 28 , 29 , 30 , 31 , 32 ]. Ubiquitination-related enzymes have been found in Yersinia pseudotuberculosis [ 33 ], Salmonella typhimurium [ 34 , 35 ], Escherichia coli [ 36 ], Legionella pneumophila [ 37 , 38 , 39 , 40 ], Streptococcus pyogenes [ 41 ], Shigella flexneri [ 42 ], Chlamydia trachomatis [ 43 ], where they support the host–pathogen molecular interaction.…”