Papillomaviruses and the host SUMOylation system.

SUMOylation of viral proteins is widespread and serves to modify or regulate the properties of those proteins. Papillomaviruses are a large group of small DNA viruses that infect the skin, leading to benign lesions (warts) that in some cases can progress to malignancy. The papillomavirus life cycle is intimately connected with the differentiation process of stratified epithelium, and several viral early proteins function to modulate the host cell environment. One of the critical early proteins is the E2 protein, which functions in both viral replication and transcription. In the present paper, we demonstrate that E2 proteins are SUMOylated and that overexpression of SUMOylation results in a dramatic increase in intracellular levels of the E2 protein. We have shown previously that there is increased SUMOylation during keratinocyte differentiation, suggesting that the levels of E2 protein may be tied to changes in the cellular SUMOylation state during differentiation. In addition to itself being regulated by SUMOylation, E2 appears to influence the SUMOylation state of one of its binding partners, the cellular transcription factor, C/EBP (CCAAT/enhancer-binding protein). Overall, these observations indicate a complex interplay between this viral protein and the host SUMOylation system.