Sumoylation at the Host-Pathogen Interface

Wilson, Van G.

As presented in this review, there are now a multitude of examples of how pathogens impact the sumoylation system. These range from increasing or decreasing sumoylation of single proteins, usually via direct binding of a pathogen protein, to global increases or decreases in sumoylation. Single protein targets typically are key cellular growth regulatory factors or are critical for host immune response. Global changes in sumoylation induced by pathogens are more dramatic, but also more difficult to understand functionally as identifying the critical targets versus irrelevant proteins is challenging. Mechanistically, some pathogen proteins act by mimicking sumoylation enzymes whereas others function by binding to and altering the activity of the endogenous host sumoylation enzymes. An emerging theme is that many of these interactions are mediated or enhanced through SIM-SUMO binding, and in some cases each binding partner has one or more SIM motifs and can also be sumoylated. This raises the possibility of combinatorial interactions that may subtly influence complex affinity, stability, or composition and thus have functional consequences. The next few years are likely to reveal additional important nuances about how pathogens utilize sumoylation to their own benefit as well as identifying many exciting new targets.