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Retinoblastoma protein acts as Pax 8 transcriptional coactivator

Oncogene volume 24, pages 6993–7001 (2005)Cite this article

Abstract

Control of cell proliferation and differentiation by the retinoblastoma protein (pRb) depends on its interactions with key cellular substrates. Available data indicate that pRb and the transcription factor Pax 8 play a crucial role in the differentiation of thyroid follicular cells. In this study, we show that pRb takes part in the complex assembled on the thyroperoxidase gene promoter acting as a transcriptional coactivator of Pax 8. Accordingly, pRb interacts with and potentiates Pax 8 transcriptional activity. In addition, we show that the downregulation of pRb gene expression, in thyrocytes, through RNA interference results in a reduction of the thyroperoxidase gene promoter activity mediated by the Pax 8-binding site. In agreement with these results and with the ability of the adenoviral protein E1A to bind pRb, we show that E1A downregulates Pax 8 activity and that such inhibition requires the E1A–Rb interaction. Furthermore, we show that the Pax 8/pRb synergy plays a role on the sodium/iodide symporter gene expression as well.

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Acknowledgements

We thank Thomas Wagner and Armando Felsani for critical reading of the manuscript. Various colleagues kindly provided many of the plasmids used in this study and we thank them for their kindness. The E1A- and E1A-Rb-encoding plasmids were a gift of B Moran (Moran, 1993). pCMV-Rb and pGST-RbLP, pCMV-107 and pCMV-130 were provided by A Felsani e M Caruso. pRbΔcdk was kindly provided by WJ Harbour. We thank MR Nicotra for immunohistochemistry. MM was supported by a fellowship of Marie Curie Training site program number HPMT-CT-2000-0010. This study was in part supported by MURST-FIRB n.RBAU19HHA-001 and by grant no. 210 Life Sciences 2002 from ASI to DC.

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Author notes

  1. Stefania Miccadei and Claudia Provenzano: These two authors contributed equally to this work

Authors and Affiliations

  1. Molecular Pathology Laboratory, Regina Elena Cancer Institute, Via delle Messi d'Oro 156, Rome, 00158, Italy

    Stefania Miccadei, Martin Mojzisek, Pier Giorgio Natali & Donato Civitareale

  2. Institute of Neurobiology and Molecular Medicine, National Council Research, Via del Fosso del Cavaliere 100, Rome, 00133, Italy

    Claudia Provenzano & Donato Civitareale

  3. Department of Medical Biology and Genetics, Charles University, Faculty of Medicine in Hradec Králové, Simkova 870, Hradec Kralove, 500 01, Czech Republic

    Martin Mojzisek

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  1. Stefania Miccadei
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Correspondence to Donato Civitareale.

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Miccadei, S., Provenzano, C., Mojzisek, M. et al. Retinoblastoma protein acts as Pax 8 transcriptional coactivator. Oncogene 24, 6993–7001 (2005). https://doi.org/10.1038/sj.onc.1208861

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