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.
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