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Nucleoside diphosphate kinases (NDPKs) in animal development

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Abstract

In textbooks of biochemistry, nucleoside diphosphate conversion to a triphosphate by nucleoside diphosphate ‘kinases’ (NDPKs, also named NME or NM23 proteins) merits a few lines of text. Yet this essential metabolic function, mediated by a multimeric phosphotransferase protein, has effects that lie beyond a simple housekeeping role. NDPKs attracted more attention when NM23-H1 was identified as the first metastasis suppressor gene. In this review, we examine these NDPK enzymes from a developmental perspective because of the tractable phenotypes found in simple animal models that point to common themes. The data suggest that NDPK enzymes control the availability of surface receptors to regulate cell-sensing cues during cell migration. NDPKs regulate different forms of membrane enclosure that engulf dying cells during development. We suggest that NDPK enzymes have been essential for the regulated uptake of objects such as bacteria or micronutrients, and this evolutionarily conserved endocytic function contributes to their activity towards the regulation of metastasis.

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Acknowledgments

A.M. is supported by the Russell Trust and the Myrovlitis Trust and the work on NDPK was supported by previous grants from the Wellcome Trust. K.T.-V. and T.V. are supported by the OTKA grant K109349. K.T.-V. is a grantee of the János Bolyai Scholarship of the Hungarian Academy of Sciences.

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Takács-Vellai, K., Vellai, T., Farkas, Z. et al. Nucleoside diphosphate kinases (NDPKs) in animal development. Cell. Mol. Life Sci. 72, 1447–1462 (2015). https://doi.org/10.1007/s00018-014-1803-0

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