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PARP co-activates B-MYB through enhanced phosphorylation at cyclin/cdk2 sites

Oncogene volume 20, pages 8167–8174 (2001)Cite this article

Abstract

PARP is a multifunctional protein that can affect genome stability, transcription control, telomere length and cell death. Recently we have reported that PARP binds to and enhances B-MYB transactivating potential. B-MYB is a potentially oncogenic transcription factor involved in mammalian cell proliferation, survival and differentiation. B-MYB gene expression is growth regulated and B-MYB protein is phosphorylated during S phase by cyclin A or E/cdk2 kinase, resulting in augmented transactivating potential. Here we show that PARP induces phosphorylation of B-MYB protein at cdk2 phosphorylation sites, since a B-MYB protein with mutated cdk2 phosphorylation sites is refractory to PARP-induced phosphorylation and co-activation in mammalian cells. We propose that PARP functions as a B-MYB co-factor by promoting cyclin/cdk2-dependent B-MYB phosphorylation. These results highlight a novel role for PARP as a factor that integrates cyclin-dependent kinases signaling with gene transcription.

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Acknowledgements

Giorgia Santilli is a recipient of a fellowship from the Fondazione Italiana per la Ricerca sul Cancro (FIRC). This work was supported in part by a grant from the Italian Ministry of Health (Progetto finalizzato Ministero della Sanita'). Danilo Perrotti and Bruno Calabretta are gratefully acknowledged for support and critical reading of the manuscript.

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Authors and Affiliations

  1. Department of Oncology and Neurosciences, Section of Medical Oncology Universita' G., D'Annunzio, 66100, Chieti, Italy

    Giorgia Santilli, Maria Neve Cervellera, Stefano Iacobelli & Arturo Sala

  2. Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, Nebraska, USA

    Teresa K Johnson & Robert E Lewis

  3. Molecular Haematology and Cancer Biology Unit, Institute of Child Health, London, WC1N, UK

    Arturo Sala

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  1. Giorgia Santilli
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  2. Maria Neve Cervellera
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  3. Teresa K Johnson
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  4. Robert E Lewis
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  5. Stefano Iacobelli
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Correspondence to Arturo Sala.

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Santilli, G., Cervellera, M., Johnson, T. et al. PARP co-activates B-MYB through enhanced phosphorylation at cyclin/cdk2 sites. Oncogene 20, 8167–8174 (2001). https://doi.org/10.1038/sj.onc.1204943

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