Sumoylation at the Host-Pathogen Interface

Wilson, Van G.

Another interesting and so far unique example of a viral protein influencing the sumoylation of a specific host protein is that of the Kaposi's sarcoma-associated herpesvirus (KSHV) viral protein kinase (vPK/ORF36) and the host KAP-1 protein [99] . KAP-1 is a transcriptional repressor that recruits chromatin remodeling proteins, such as HDACs, to inactivate cellular promoters [100] . KAP-1 is sumoylated at three lysines, and the conjugated SUMO moieties contribute to binding of the chromatin remodeling proteins and hence the repressive function of KAP-1 [101] . KAP-1 is also phosphorylated, and phosphorylation of serine 824 reduces sumoylation at all three lysines and thus decreases the repressive activity of KAP-1 [102] . Chang et al. subsequently presented evidence that KAP-1 is involved in the switch between latent and lytic growth for KSHV [99] . Importantly, they showed that the viral kinase could phosphorylate KAP-1 leading to decreased KAP-1 sumoylation and decreased occupancy of KAP-1 on viral promoters. These results point to a model where KSHV uses phosphorylation of KAP-1 by the vPK as a mechanism to antagonize KAP-1 sumoylation and overcome KAP-1 repression, thus favoring lytic replication over latency.