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Sp100 is important for the stimulatory effect of homeodomain-interacting protein kinase-2 on p53-dependent gene expression

Oncogene volume 22, pages 8731–8737 (2003)Cite this article

Abstract

HIPK2 shows overlapping localization with p53 in promyelocytic leukemia (PML) nuclear bodies (PML-NBs) and functionally interacts with p53 to increase gene expression. Here we demonstrate that HIPK2 and the PML-NB resident protein Sp100 synergize for the activation of p53-dependent gene expression. Sp100 and HIPK2 interact and partially colocalize in PML-NBs. The cooperation of HIPK2 and Sp100 for the induction of p21Waf1 is completely dependent on the presence of p53 and the kinase function of HIPK2. Downregulation of Sp100 levels by expression of siRNA does not interfere with p53-mediated transcription, but obviates the enhancing effect of HIPK2. In summary, these experiments reveal a novel function for Sp100 as a coactivator for HIPK2-mediated p53 activation.

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Acknowledgements

Our work was supported by grants from the Deutsche Forschungsgemeinschaft (Schm 1417/3-1), Fonds der chemischen Industrie, EU project (QLK3-CT-2000-00463) sponsored by the Schweizerisches Bundesamt für Bildung und Wissenschaft, Oncosuisse, Schweizerischer Nationalfonds, Association for International Cancer Research, ‘Stiftung zur Förderung der wissenschaftlichen Forschung an der Universität Bern' and a grant from the Roche Research Foundation awarded to AM and MLS. The work of HS, TGH, HS and HW was supported by grants from the ‘Stiftung zur Bekämpfung Neuroviraler Erkrankungen', the Deutsche Krebshilfe (Wi2-10-1624) and the Deutsche Forschungsgemeinschaft (HO 2438/2-1; WI664/6-2). The Heinrich-Pette-Institut is supported by the Freie und Hansestadt Hamburg and the Bundesministerium für Gesundheit.

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Authors and Affiliations

  1. Division of Immunochemistry (G0200), German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg, D-69120, Germany

    Andreas Möller, Elisabeth Klimczak & Wulf Dröge

  2. Department of Chemistry and Biochemistry, University of Bern, University of Bern, Freiestr. 3, Bern, 3012, Switzerland

    Andreas Möller, Ekaterina Gresko, Katharina Schmid Lüdi & M Lienhard Schmitz

  3. Department of General Virology, Heinrich-Pette-Institute for Experimental Virology and Immunology, Martinistrasse 52, D-20251, Hamburg, D-20251, Germany

    Hüseyin Sirma, Thomas G Hofmann, Hannah Staege & Hans Will

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  1. Andreas Möller
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  2. Hüseyin Sirma
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Correspondence to M Lienhard Schmitz.

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Möller, A., Sirma, H., Hofmann, T. et al. Sp100 is important for the stimulatory effect of homeodomain-interacting protein kinase-2 on p53-dependent gene expression. Oncogene 22, 8731–8737 (2003). https://doi.org/10.1038/sj.onc.1207079

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