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Notch3: from subtle structural differences to functional diversity

Oncogene volume 27, pages 5092–5098 (2008)Cite this article

Abstract

The Notch3 gene was identified, at the beginning of 90s, as the third mammalian Notch and was initially reported as being expressed in proliferating neuroepithelium. Since then, increasing evidence has demonstrated a number of structural and functional differences between Notch3 and both Notch1 and Notch2, which exhibit the highest structural similarity among the four mammalian Notch receptors. Possibly due to its more restricted tissue distribution, targeted deletion of murine Notch3 does not lead to embryonic lethality as is observed with targeted deletion of Notch1 and Notch2. However, genetic mutation, amplification and deregulated expression of Notch3 have been correlated with the disruption of cell differentiation in transgenic mice and to development of diseases in mice and humans. This review discusses the possible relationships between the structural differences and the nonredundant roles that Notch3 plays in the pathogenesis of the human disease cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy and in the regulation of murine T-cell differentiation and leukemogenesis.

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Acknowledgements

We thank members of Screpanti's laboratory, whose comments and work have contributed to the realization of this review. Work in the authors' laboratory is supported by Grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC) and the Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR).

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  1. Department of Experimental Medicine, Laboratory of Molecular Pathology, Sapienza University of Rome, Rome, Italy

    D Bellavia, S Checquolo, A F Campese, M P Felli, A Gulino & I Screpanti

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  1. D Bellavia
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  2. S Checquolo
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  3. A F Campese
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  4. M P Felli
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Correspondence to I Screpanti.

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Bellavia, D., Checquolo, S., Campese, A. et al. Notch3: from subtle structural differences to functional diversity. Oncogene 27, 5092–5098 (2008). https://doi.org/10.1038/onc.2008.230

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