The human papillomavirus oncogenic protein, E6, interacts with a number of 
cellular proteins, and for some targets, E6 directs their degradation through 
the ubiquitin-proteasome pathway. Post-translational modification with 
ubiquitin-like modifiers, such as SUMO, also influences protein activities, 
protein-protein interactions, and protein stability. We report that the high 
risk HPVE6 proteins reduce the intracellular quantity of the sole SUMO 
conjugation enzyme, Ubc9, concomitant with decreased host sumoylation. E6 did 
not significantly influence transcription of Ubc9, indicating that the effects 
were likely at the protein level. Consistent with typical E6-mediated 
proteasomal degradation, E6 bound to Ubc9 in vitro, and required E6AP for 
reduction of Ubc9 levels. Under stable E6 expression conditions in 
differentiating keratinocytes there was a decrease in Ubc9 and a loss of 
numerous sumoylated targets indicating a significant perturbation of the normal 
sumoylation profile. While E6 is known to inhibit PIASy, a SUMO ligase, our 
results suggest that HPV E6 also targets the Ubc9 protein to modulate host cell 
sumoylation, suggesting that the sumoylation system may be an important target 
during viral reproduction and possibly the subsequent development of cervical 
cancer.