Mucosal human papillomaviruses (HPVs) are the causative agents of a number of 
human pathologies, including benign condylomas, as well as of the majority of 
cervical cancers and their high-grade precursor lesions. Although the viral E6 
protein is known to be essential for driving malignant progression of 
HPV-infected cells, there are still many uncertainties about its mode of action. 
In this study, we have analysed the intracellular distribution of the E6 
oncoproteins from the high-risk HPV-18 and the low-risk HPV-11. We show that 
both E6 proteins localize within the nucleus in nuclear bodies that are confocal 
with the promyelocytic leukaemia (PML) protein. Using a panel of different PML 
isoforms, we demonstrate specific co-localization between the E6 proteins and 
PML isoforms I-IV, but not with PML isoforms V and VI. We also demonstrate the 
interaction between E6 and a subset of PML isoforms in vivo. As a consequence of 
this interaction, the insoluble form of PML IV is destabilized by HPV-18 E6 
through a proteasome-dependent pathway. Interestingly, both HPV-11 E6 and HPV-18 
E6 can readily overcome PML IV-induced cellular senescence in primary cells. 
These results show separable functions for different PML isoforms that are 
specifically targeted by the HPV E6 oncoproteins.