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The retinoblastoma susceptibility gene product/Sp1 signalling pathway is modulated by Ca2+/calmodulin kinases II and IV activity

Oncogene volume 18, pages 2762–2769 (1999)Cite this article

Abstract

To investigate the possible link between Ca2+ signalling and cell cycle control we analysed Ca2+/calmodulin kinases (CamK) interaction with the retinoblastoma susceptibility gene product/SP1 pathway. CamK II and IV activate c-fos transcription through a short promoter region (−99 to −53) containing the retinoblastoma control element (RCE) and a cAMP response element (CRE) related sequences. Deletion analysis revealed that the RCE is a major CamK responsive element and is sufficient to confer CamK and Ca2+ regulation to a minimal promoter. Direct interactions between SP1 and RCE were confirmed by gel shift experiments. Using transient transfection experiments, we show that CamK-dependent transcription is regulated by the retinoblastoma (Rb) susceptibility gene product and the p107 Rb related protein. However, the stimulatory effects of CamKs and Rb on c-fos are blocked by overexpression of both proteins. These effects appear to be directly mediated by SP1 as shown by the use of a Gal4/SP1 fusion proteins. In conclusion, CamK II and IV, two major Ca2+-dependent intracellular effectors, may represent a molecular link between this second messenger transduction pathway and effectors that control cell cycle progression through Rb/SP1 signalling pathway.

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Acknowledgements

The authors thank Dr S Brooks for critical review of the manuscript, C Nelson, L Le Personnic and F Herzog for their efficient technical support. The authors are grateful to Dr G Roeder (New York, USA), Dr RC Mulligan (Boston, USA), Dr TD Gilmore (Boston, USA), Dr ME Ewen (Boston, USA), and Dr R Maurer (Portland, USA) for the generous gift of recombinant material. This work was supported by ARC (grants n° 6089 and 9821 to JP Loeffler).

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  1. Frédéric Sohm and Christian Gaiddon: F Sohm and C Gaiddon contributed equally to this study

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  1. IPCB, UMR 7519 CNRS, 21 rue René Descartes, Strasbourg, 67084, Cedex, France

    Frédéric Sohm, Christian Gaiddon, Muriel Antoine, Anne-Laurence Boutillier & Jean-Philippe Loeffler

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  1. Frédéric Sohm
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Sohm, F., Gaiddon, C., Antoine, M. et al. The retinoblastoma susceptibility gene product/Sp1 signalling pathway is modulated by Ca2+/calmodulin kinases II and IV activity. Oncogene 18, 2762–2769 (1999). https://doi.org/10.1038/sj.onc.1202634

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