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.

Oncogene
|July 20, 2010
PubMed

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.

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