Sumoylation at the Host-Pathogen Interface

Wilson, Van G.

PML NBs include a variety of other cellular proteins, many of which are also sumoylated such as Sp100 [122] and DAXX [123] . An early report indicated that HSV ICP0 reduced the sumoylation of Sp100 as well as PML [108] , and a subsequent study found that ICP0 also induced proteasomal degradation of Sp100 [124] . While the mechanistic basis for the reduction in Sp100 sumoylation has not been explored, it is tempting to speculate that it could be through the same STUbL activity that promotes PML degradation. Likewise, early proteins from other herpesvirus family members that can modulate the sumoylation PML may have similar effects on other sumoylated proteins in the NBs. In addition to early proteins, there is now one well documented study indicating that a cytomegalovirus tegument protein, pp71, enhances sumoylation of Daxx [125] . Sumoylation of Daxx requires direct binding of pp71 but does not require Daxx to be in PML NBs. Furthermore, pp71 does not lead to a general increase in cellular sumoylation so this effect appears restricted to Daxx or a very limited number of substrates. Pp71 did not interact with Ubc9 so it is unclear if pp71 is acting as a SUMO ligase for Daxx or stimulating Daxx sumoylation through some less direct mechanism. Functionally, pp71 could still induce degradation of a Daxx SUMO site mutant so sumoylation is not required for that activity. Additionally, no effect of sumoylation on Daxx transcriptional repression was observed so the biological significance of this pp71 mediated enhancement in sumoylation remains obscure.