SUMO modification of E1B-55K oncoprotein regulates isoform-specific binding to the tumour suppressor protein PML.
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.
Wimmer
P
P
Department of Molecular Virology, Heinrich-Pette-Institute for Experimental Virology and Immunology, Hamburg, Germany.
Schreiner
S
S
Everett
R D
RD
Sirma
H
H
Groitl
P
P
Dobner
T
T
D017501:Adenovirus E1B Proteins / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002472:Cell Transformation, Viral / Q000502:physiology*; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D009687:Nuclear Proteins / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D025842:SUMO-1 Protein / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D017501:Adenovirus E1B Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D000071156:Promyelocytic Leukemia Protein; D020033:Protein Isoforms; D025842:SUMO-1 Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human