Related Experiment Video
Updated: Jun 10, 2026

SUMO-Binding Entities (SUBEs) as Tools for the Enrichment, Isolation, Identification, and Characterization of the SUMO Proteome in Liver Cancer
Published on: November 1, 2019
SUMO modification of E1B-55K oncoprotein regulates isoform-specific binding to the tumour suppressor protein PML
P Wimmer1, S Schreiner, R D Everett
1Department of Molecular Virology, Heinrich-Pette-Institute for Experimental Virology and Immunology, Hamburg, Germany.
Abstract:
The E1B-55K product from human adenovirus is a substrate of the small ubiquitin-related modifier (SUMO)-conjugation system. SUMOylation of E1B-55K is required to transform primary mammalian cells in cooperation with adenovirus E1A and to repress p53 tumour suppressor functions. The biochemical consequences of SUMO1 conjugation of 55K have so far remained elusive. Here, we report that E1B-55K physically interacts with different isoforms of the tumour suppressor protein promyelocytic leukaemia (PML). We show that E1B-55K binds to PML isoforms IV and V in a SUMO1-dependent and -independent manner. Interaction with PML-IV promotes the localization of 55K to PML-containing subnuclear structures (PML-NBs). In virus-infected cells, this process is negatively regulated by other viral proteins, indicating that binding to PML is controlled through reversible SUMOylation in a timely coordinated manner. These results together with earlier work are consistent with the idea that SUMOylation regulates targeting of E1B-55K to PML-NBs, known to control transcriptional regulation, tumour suppression, DNA repair and apoptosis. Furthermore, they suggest that SUMO1-dependent modulation of p53-dependent growth suppression through E1B-55K PML-IV interaction has a key role in adenovirus-mediated cell transformation.
Insights
Human adenovirus E1B-55K protein interacts with the promyelocytic leukaemia (PML) protein, influencing cell transformation. SUMOylation regulates E1B-55K targeting to PML nuclear bodies, impacting p53 tumor suppressor functions.
Area of Science:
- Molecular biology
- Virology
- Cancer research
Background:
- Human adenovirus E1B-55K is crucial for cell transformation and p53 repression.
- E1B-55K is modified by the small ubiquitin-related modifier (SUMO)-conjugation system.
- The precise role of SUMOylation in E1B-55K function remained unclear.
Purpose of the Study:
- To investigate the biochemical consequences of SUMO1 conjugation on E1B-55K.
- To determine the interaction between E1B-55K and promyelocytic leukaemia (PML) protein isoforms.
- To elucidate the role of SUMOylation in regulating E1B-55K localization and function.
Main Methods:
- Co-immunoprecipitation assays to detect protein interactions.
- Immunofluorescence microscopy to visualize protein localization.
- Analysis of viral protein regulation in infected cells.
Main Results:
- E1B-55K interacts with PML isoforms IV and V, independent of SUMO1.
- SUMOylation-independent binding to PML-IV directs E1B-55K to PML nuclear bodies (PML-NBs).
- Viral proteins regulate this interaction in infected cells, suggesting SUMOylation controls E1B-55K targeting to PML-NBs.
Conclusions:
- SUMOylation regulates E1B-55K targeting to PML-NBs, which are involved in transcriptional regulation, DNA repair, and apoptosis.
- SUMO1-dependent modulation of E1B-55K and PML-IV interaction plays a role in adenovirus-mediated cell transformation by affecting p53 function.
Related Concept Videos
Abnormal Proliferation
Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein.
Regulation of Nuclear Protein Sorting
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Regulation of Expression at Multiple Steps
Induced Pluripotent Stem Cells
Somatic cells are...

