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The NM23 family in development

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Abstract

The NM23 (non-metastatic 23) family is almost universally conserved across all three domains of life: eubacteria, archaea and eucaryotes. Unicellular organisms possess one NM23 ortholog, whilst vertebrates possess several. Gene multiplication through evolution has been accompanied by structural and functional diversification. Many NM23 orthologs are nucleoside diphosphate kinases (NDP kinases), but some more recently evolved members lack NDP kinase activity and/or display other functions, for instance, acting as protein kinases or transcription factors. These members display overlapping but distinct expression patterns during vertebrate development. In this review, we describe the functional differences and similarities among various NM23 family members. Moreover, we establish orthologous relationships through a phylogenetic analysis of NM23 members across vertebrate species, including Xenopus laevis and zebrafish, primitive chordates and several phyla of invertebrates. Finally, we summarize the involvement of NM23 proteins in development, in particular neural development. Carcinogenesis is a process of misregulated development, and NM23 was initially implicated as a metastasis suppressor. A more detailed understanding of the evolution of the family and its role in vertebrate development will facilitate elucidation of the mechanism of NM23 involvement in human cancer.

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Acknowledgements

We are grateful to Dr. T. Mochizuki for contribution of the in situ images. This work was supported by Cancer Research, UK, and Fight for Sight.

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Authors and Affiliations

  1. Department of Oncology, Hutchison/MRC Research Centre, University of Cambridge, Hills Road, Cambridge, CB2 0XZ, UK

    Aikaterini Bilitou, Julie Watson & Shin-ichi Ohnuma

  2. Wellcome Trust Centre for Gene Regulation and Expression, University of Dundee, Dow Street, Dundee, DD1 5EH, UK

    Anton Gartner

  3. UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK

    Shin-ichi Ohnuma

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  1. Aikaterini Bilitou
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  2. Julie Watson
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  3. Anton Gartner
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  4. Shin-ichi Ohnuma
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Correspondence to Shin-ichi Ohnuma.

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Bilitou, A., Watson, J., Gartner, A. et al. The NM23 family in development. Mol Cell Biochem 329, 17–33 (2009). https://doi.org/10.1007/s11010-009-0121-6

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