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  • Original Paper
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Neoplastic transformation by Notch is independent of transcriptional activation by RBP-J signalling

Oncogene volume 19, pages 556–561 (2000)Cite this article

Abstract

Signalling through the transmembrane receptor Notch is triggered by ligand binding, which induces the proteolytic cleavage of the Notch protein. This cleavage generates an intracellular fragment of the Notch protein (Notch-IC), which translocates into the nucleus and modifies transcription of target genes through its association with the RBP-J protein. Thus, the isolated Notch-IC protein represents the constitutively activated receptor. We have performed a deletion analysis of Notch IC in order to identify the transferable transactivation domain of Notch-IC and the minimal domain of Notch-IC required for RBP-J dependent transactivational activation. Functionally, Notch-IC has been linked to cell fate decision in development and oncogenesis in vivo. In vitro, Notch-IC can cooperate in neoplastic transformation of baby rat kidney cells with the adenoviral E1A protein. We have defined the minimal domain of Notch-IC required for E1A cotransformation. This domain, consisting of the ankyrin repeats of Notch-IC only, can neither activate RBP-J dependent transcription nor does it carry a transactivation domain. Therefore, the ankyrin repeat domain of Notch-IC might trigger novel pathways relevant for transformation but unrelated to RBP-J signalling.

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Acknowledgements

We thank R Kageyama for the generous gift of the Hes-1 and Hes-5 promoter constructs, C Sardet for the pHACS1 expression plasmid and A Kieser for the rasv12 expression construct. MTE1A cells were kindly provided by J Cook. We also thank GW Bornkamm and D Eick for critical reading and discussions of the manuscript. This work was supported by grants from the Deutsche Forschungsgemeinschaft (SFB455), the Stipendium für Infektionsforschung des Deutschen Krebsforschungszentrums and the Strategy Fonds of the Helmholtz Gemeinschaft.

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  1. Institut für Klinische Molekularbiologie und Tumorgenetik, GSF-Forschungszentrum für Umwelt und Gesundheit, Marchioninistr. 25, München, 81377, Germany

    Elisabeth Dumont, Klaus Peter Fuchs, Guido Bommer, Barbara Christoph & Bettina Kempkes

  2. Institut für Molekulare Immunologie, GSF-Forschungszentrum für Umwelt und Gesundheit, Marchioninistr. 25, München, 81377, Germany

    Elisabeth Kremmer

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  1. Elisabeth Dumont
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Dumont, E., Fuchs, K., Bommer, G. et al. Neoplastic transformation by Notch is independent of transcriptional activation by RBP-J signalling. Oncogene 19, 556–561 (2000). https://doi.org/10.1038/sj.onc.1203352

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