Sumoylation at the Host-Pathogen Interface

Wilson, Van G.

As opposed to the global reduction in sumoylation by LLO and E6, the Epstein-Barr virus (EBV) LMP1 oncoprotein targets Ubc9 and causes enhanced global sumoylation [92] . LMP1 is the latent membrane protein and possesses six transmembrane domains and a 200-amino acid C-terminal cytoplasmic tail containing three CTAR motifs. Bentz et al. showed that LMP1 binds Ubc9 through CTAR3 and that the interaction requires enzymatically active Ubc9. The LMP1-Ubc9 interaction leads to an increase in total SUMO conjugates with SUMO1, SUMO2, or SUMO3, and this increase is eliminated by a CTAR3 deletion. Abrogating the increase in sumoylation with the CTAR3 deletion does not cause an effect on host cell growth, but does reduce the ability of LMP1 to stimulate cell migration in a scratch assay, indicating that LMP1's ability to increase sumoylation does have biological implications. Mechanistically, LMP1 did not cause any change in Ubc9 protein levels so the authors proposed that LMP1 may be acting as a SUMO ligase, though the critical targets for the migration effect remain to be determined. A similar global increase in sumoylation was also observed during influenza A virus infection of HEK293, A549, MDCK, and Vero cells [93] . The viral protein mediator was not identified, and there was no change in intracellular levels of Ubc9, SAE1, or SAE2, so the viral target that causes this increase in sumoylation is unknown. However, the increase in sumoylation could not be mimicked by interferon treatment alone and did not occur with UV inactivated virus, suggesting that one or more viral products produced during active infection were responsible. It will be interesting to see if this effect is somehow mediated through Ubc9 as for LMP1 or if it involves a different mechanism.