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Self-association of adenovirus type 5 E1B-55 kDa as well as p53 is essential for their mutual interaction

Oncogene volume 29, pages 1773–1786 (2010)Cite this article

Abstract

The adenovirus type 5 E1B-55 kDa oncoprotein forms a complex with the tumor suppressor p53 and inactivates it. E1B-55 kDa and p53 are each capable of forming oligomers. We mapped the oligomerization domain of E1B-55 kDa to the central portion of the protein. Disturbing E1B-55 kDa self-association by point mutations at residues 285/286 or 307 not only impairs its intracellular localization to the cytoplasmic clusters, but in addition, its association with p53. Strikingly, tetramerization of p53 is also required for efficient association with E1B-55 kDa. Moreover, two different E1B-55 kDa mutants defective for p53 binding but proficient for oligomerization can trans-complement each other for p53 relocalization. We propose that the homo-oligomerization of each component enables efficient interaction between E1B-55 kDa and p53 through increased avidity.

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Acknowledgements

We thank C Hippel and A Dickmanns for excellent technical assistance. We thank M Oren (Rehovot) and K Vousden (Glasgow) for plasmids and cells. Our work was supported by the German Cancer Aid/Dr Mildred Scheel Stiftung, the EU 6th Framework Program (Integrated Project Active p53), the German Research Foundation (DFG), the Wilhelm Sander Stiftung, the Statens Sundhedsvidenskabelige Forskningsråd of Denmark, the Danish Cancer Society, the Fonden til Lægevidenskabens Fremme, the Novonordisk fonden, the MSc/PhD Molecular Biology Program at the University of Göttingen, and The Göttingen Graduate School for Neurosciences and Molecular Biosciences (GGNB).

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  1. Department of Molecular Oncology, Göttingen Center of Molecular Bioscience, Ernst Caspari Haus, University of Göttingen, Göttingen, Germany

    M Morawska-Onyszczuk & M Dobbelstein

  2. Department of Molecular Virology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland

    M Morawska-Onyszczuk & K Bieńkowska-Szewczyk

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  1. M Morawska-Onyszczuk
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Correspondence to M Dobbelstein.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Morawska-Onyszczuk, M., Bieńkowska-Szewczyk, K. & Dobbelstein, M. Self-association of adenovirus type 5 E1B-55 kDa as well as p53 is essential for their mutual interaction. Oncogene 29, 1773–1786 (2010). https://doi.org/10.1038/onc.2009.461

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