Sumoylation at the Host-Pathogen Interface

Wilson, Van G.

From modest beginnings as a possibly minor modification system, sumoylation has emerged as a major regulatory network that involves hundreds to thousands of proteins through direct SUMO conjugation and SIM motif-mediated interactions with sumoylated proteins. Sumoylation is now known to be involved in major cellular events including transcriptional regulation, cell cycle control, DNA repair, RNA processing, chromatin remodeling, and nucleocytoplasmic trafficking. Viruses and certain bacterial pathogens must utilize many of these cellular processes to facilitate their own gene expression and genome replication. Consequently, it is not surprising that many pathogens have evolved proteins that are regulated by sumoylation or can usurp certain aspects of the host sumoylation system to reprogram the cellular environment to be more permissive for pathogen persistence or reproduction. The recent finding that sumoylation is involved in regulating aspects of intrinsic and innate immunity, provides another rationale for why pathogens, particularly viruses, target the sumoylation system. The ability to avoid or reduce initial host defenses is obviously critical to establishing a productive infection, and dysregulating sumoylation generally or for specific targets appears to be a common mechanism for pathogens to thwart these defenses.