Although modulation of the cellular tumor-suppressor p53 is considered to have 
the major role in E1A/E1B-55K-mediated tumorigenesis, other promyelocytic 
leukemia nuclear body (PML-NB)/PML oncogenic domain (POD)-associated factors 
including SUMO, Mre11, Daxx, as well as the integrity of these nuclear bodies 
contribute to the transformation process. However, the biochemical consequences 
and oncogenic alterations of PML-associated E1B-55K by SUMO-dependent PML-IV and 
PML-V interaction have so far remained elusive. We performed mutational analysis 
to define a PML interaction motif within the E1B-55K polypeptide. Our results 
showed that E1B-55K/PML binding is not required for p53, Mre11 and Daxx 
interaction. We also observed that E1B-55K lacking subnuclear PML localization 
because of either PML-IV or PML-V-binding deficiency was no longer capable of 
mediating E1B-55K-dependent SUMOylation of p53, inhibition of p53-mediated 
transactivation or efficiently transforming primary rodent cells. These results 
together with the observation that E1B-55K-dependent SUMOylation of p53 is 
required for efficient cell transformation, provides evidence for the idea that 
the SUMO ligase activity of the E1B-55K viral oncoprotein is intimately linked 
to its growth-promoting oncogenic activities.