Abstract
Eukaryotic cells utilize the ubiquitin (Ub) system for maintaining a balanced functioning of cellular pathways. Although the Ub system is exclusive to eukaryotes, prokaryotic bacteria have developed an armory of Ub ligase enzymes that are capable of employing the Ub systems of various hosts, ranging from plant to animal cells. These enzymes have been acquired through the evolution and can be classified into three main classes, RING (really interesting new gene), HECT (homologous to the E6-AP carboxyl terminus) and NEL (novel E3 ligases). In this review we describe the roles played by different classes of bacterial Ub ligases in infection and pathogenicity. We also provide an overview of the different mechanisms by which bacteria mimic specific components of the host Ub system and outline the gaps in our current understanding of their functions. Additionally, we discuss approaches and experimental tools for validating this class of enzymes as potential novel antibacterial therapy targets.
Highlights
Throughout evolution, prokaryotes have acquired an intricate array of molecular armory that facilitates the hijacking of host cells
The power of Y2H technology in allowing the fast interrogation of binary interactions between bacterial Ub ligase-like effectors and host substrates on a proteome-wide scale was instrumental for the identification of numerous host-pathogen interactions [97, 98]
Of utmost importance is the development of methodology enabling the identification of proteins that are ubiquitylated upon infection of host cells by various pathogens, which should significantly improve the identification of high-confidence targets that are relevant for bacterial infection
Summary
Eukaryotic cells utilize the ubiquitin (Ub) system for maintaining a balanced functioning of cellular pathways. The Ub system is exclusive to eukaryotes, prokaryotic bacteria have developed an armory of Ub ligase enzymes that are capable of employing the Ub systems of various hosts, ranging from plant to animal cells. These enzymes have been acquired through the evolution and can be classified into three main classes, RING (really interesting new gene), HECT (homologous to the E6-AP carboxyl terminus) and NEL (novel E3 ligases).
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