title: Sp100A is a tumor suppressor that activates p53-dependent transcription and counteracts E1A/E1B-55K-mediated transformation.
abstract: Human adenoviruses (HAdV) are used as a model system to investigate tumorigenic processes in mammalian cells where the viral oncoproteins E1A and E1B-55K are absolutely required for oncogenic transformation, because they simultaneously accelerate cell cycle progression and inhibit tumor suppressor proteins such as p53, although the underlying mechanism is still not understood in detail. In our present study, we provide evidence that E1B-55K binding to the PML-NB component Sp100A apparently has an essential role in regulating adenovirus-mediated transformation processes. Specifically, when this E1B-55K/Sp100A complex recruits p53, Sp100A-induced activation of p53 transcriptional activity is effectively abolished. Hence, Sp100A exhibits tumor-suppressive activity, not only by stabilizing p53 transactivation but also by depressing E1A/E1B-55K-mediated transformation. E1B-55K counteracts this suppressive activity, inducing Sp100A SUMOylation and sequestering the modified cellular factor into the insoluble matrix of the nucleus or into cytoplasmic inclusions. These observations provide novel insights into how E1B-55K modulates cellular determinants to maintain growth-promoting activity during oncogenic processes and lytic infection.
authors.affiliation: Department of Viral Transformation, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Berscheminski
authors.affiliation: Department of Viral Transformation, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Brun
authors.affiliation: Department of Viral Transformation, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Speiseder
authors.affiliation: Department of Viral Transformation, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Wimmer
authors.affiliation: Department of Viral Transformation, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: W H
authors.initials: WH
authors.lastname: Ip
authors.affiliation: Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Terzic
authors.affiliation: Department of Viral Transformation, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Dobner
authors.affiliation: Department of Viral Transformation, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.|Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Schreiner
mesh_terms: D017501:Adenovirus E1B Proteins / Q000235:genetics / Q000502:physiology*; D034961:Antigens, Nuclear / Q000378:metabolism*; D001324:Autoantigens / Q000378:metabolism*; D002472:Cell Transformation, Viral / Q000235:genetics / Q000502:physiology*; D006801:Humans; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D017501:Adenovirus E1B Proteins; D034961:Antigens, Nuclear; D001324:Autoantigens; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C066642:SP100 protein, human