Abstract
Nm23-H1 (also known as NDPKA) and h-Prune form a protein complex that is part of a little-understood protein network. Modifications of this complex correlate with cancer status. Here, we focus on the role of the Nm23-H1–h-Prune complex in cellular physiology, through an analysis of the balance between the ‘bound’ and ‘non-bound’ states of Nm23-H1 and h-Prune, whereby we speculate on the ‘read-out’ during cell homeostasis under non-balanced conditions. We have analysed the biochemical activities of both Nm23-H1 and h-Prune alone and in combination, focussing on the anti-metastatic activity of Nm23-H1. We have then investigated the cellular mechanisms responsible for the formation of the Nm23-H1–h-Prune complex. To evaluate the importance of the equilibrium between the formation of the Nm23-H1–h-Prune complex and the ‘free’ levels of Nm23-H1 and h-Prune, we propose a model based on a pro-cancer condition where this equilibrium is negatively affected.
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Acknowledgements
This work was supported by grants from the FP6-E.E.T pipeline LSH-CT-2006-037260, TuMIC LSH-CT HEALTH-2007-2.4.1-6 and Associazione Italiana per la Lotta al Neuroblastoma, an Associazione Italiana per la Lotta al Neuroblastoma Research Fellowship (A.G.) and an AIRC 2007-8 grant. We also thank the CEINGE services laboratory for several of the strategies that were developed for the use of proteomic and translational approaches within these projects.
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Galasso, A., Zollo, M. The Nm23-H1–h-Prune complex in cellular physiology: a ‘tip of the iceberg’ protein network perspective. Mol Cell Biochem 329, 149–159 (2009). https://doi.org/10.1007/s11010-009-0115-4
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DOI: https://doi.org/10.1007/s11010-009-0115-4