Plays a major role to prevent cellular inhibition of viral genome replication. Assembles an SCF-like E3 ubiquitin ligase complex based on the cellular proteins ELOB, ELOC, CUL5 and RBX1, in cooperation with viral E4orf6. This viral RING-type ligase ubiquitinates cellular substrates and targets them to proteasomal degradation: TP53/p53, LIG4, MRE11-RAD50-NBS1 (MRN) complex, ITGA3, DAXX and BLM. Degradation of host TP53/p53 activity is essential for preventing E1A-induced TP53 accumulation that would otherwise lead to cell apoptosis and growth arrest. E1B-55K also inactivates TP53 transcription-factor activity by binding its transactivation domain. E1B-55K also functions as a SUMO1 E3 ligase for TP53 which causes the latter to be sequestered in promyelocytic leukemia (PML) nuclear bodies thereby contributing to maximal inhibition of TP53 function. Interacts with the transactivation domain of TP53 (via N-terminus); this interaction leads to the inhibition of TP53 function and/or its degradation. Interacts with host PML-4 and PML-5; this interaction promotes efficient subnuclear targeting of E1B-55K to PML nuclear bodies. Interacts with E4-ORF3 protein. Interacts with E4-ORF6 protein. Interacts with host DAXX protein; this interaction might alterate the normal interactions of DAXX, PML, and p53, which may contribute to cell transformation. Colocalizes with host TP53 to host PML nuclear bodies. PML localization of E1B-55K is necessary for E1B-55K-dependent SUMOylation of TP53. Contains a PML interaction motif that allows the subnuclear PML localization. Belongs to the adenoviridae E1B 55 kDa protein family.