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Polyomavirus small T antigen transactivates genes by its ability to provoke the synthesis and the stabilization of MYC

Oncogene volume 26, pages 6356–6360 (2007)Cite this article

Abstract

DNA tumor viruses are capable of driving quiescent cells into the cell cycle. In case of polyomaviridae, two viral proteins, the large and the small (ST) T antigens are responsible for this outcome. ST interacts with the protein phosphatase PP2A and with chaperons of the dnaK type and leads to the transactivation of several genes, which play a role in S-phase induction. One of these is the transcription factor myelocytomatosis (MYC), which by itself is an important regulator of growth. Microarray analysis has revealed several ST-induced genes, which are also targets of MYC; hence, ST may induce these genes via MYC. Experiments shown here are in line with this assumption. MYC-regulated genes are induced by ST at later times than MYC and a MYC responsive promoter is stimulated by ST. Regulation of MYC occurs through signal transduction pathways, which are co-ordinated by PP2A suggesting that they may be targets of ST. Here, we show that this is the case as important kinases involved in these pathways appear in the active phosphorylated form in the presence of ST. Inhibition of these kinases interferes with MYC induction and inhibition of MYC activity blocks ST-mediated transactivation.

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Acknowledgements

We are grateful to Peter Angel (DKFZ) and to Roland Foisner and Ernst Müllner from our department for kindly providing reagents. This work was supported by FWF and the Herzfelder Foundation.

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  1. B Klucky

    Present address: 2Current address: DKFZ, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg D-69221, Germany.,

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  1. Division of Molecular Biology, Department of Medical Biochemistry, MFPL, Medical University of Vienna, Vienna, Austria

    B Klucky & E Wintersberger

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  1. B Klucky
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  2. E Wintersberger
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Correspondence to E Wintersberger.

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Klucky, B., Wintersberger, E. Polyomavirus small T antigen transactivates genes by its ability to provoke the synthesis and the stabilization of MYC. Oncogene 26, 6356–6360 (2007). https://doi.org/10.1038/sj.onc.1210458

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  • DOI: https://doi.org/10.1038/sj.onc.1210458

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