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  • Original Paper
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Evidence for interaction between human PRUNE and nm23-H1 NDPKinase

Oncogene volume 18, pages 7244–7252 (1999)Cite this article

Abstract

We have isolated a human and murine homologue of the Drosophila prune gene through dbEST searches. The gene is ubiquitously expressed in human adult tissues, while in mouse developing embryos a high level of expression is confined to the nervous system particularly in the dorsal root ganglia, cranial nerves, and neural retina. The gene is composed of eight exons and is located in the 1q21.3 chromosomal region. A pseudogene has been sequenced and mapped to chromosomal region 13q12. PRUNE protein retains the four characteristic domains of DHH phosphoesterases. The synergism between prune and awdK-pn in Drosophila has led various authors to propose an interaction between these genes. However, such an interaction has never been supported by biochemical data. By using interaction-mating and in vitro co-immunoprecipitation experiments, we show for the first time the ability of human PRUNE to interact with the human homologue of awd protein (nm23-H1). In contrast, PRUNE is impaired in its interaction with nm-23-H1-S120G mutant, a gain-of-function mutation associated with advanced neuroblastoma stages. Consistently, PRUNE and nm23-H1 proteins partially colocalize in the cytoplasm. The data presented are consistent with the view that PRUNE acts as a negative regulator of the nm23-H1 protein. We discuss how PRUNE regulates nm23-H1 protein and postulate possible implications of PRUNE in neuroblastoma progression.

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Acknowledgements

We would like to thank Loris Bernard, Stefano Cairo, Mariella Crippa, Maria Cucciardi, Claudio Gattuso, Sabrina Giglio, Monica Repetto and Rossana Tonlorenzi for technical help, the YAC screening Center (Iger) for providing access to the Human PAC library, Gyorgy Simon and the Informatics Core for computing assistance and database support. We thank Professors Andreas Gal and Shomi Bhattacharya for sharing the DNA material corresponding to the Danish and English families affected by adRP18. Finally, we would like to thank Sandro Banfi, Giuseppe Borsani, Germana Meroni and Valeria Marigo for critical review of the manuscript and Anne Simon and Melissa Smith for manuscript preparation. This research was sponsored by a Telethon Fellowship for Foreigners in Italy to A Reymond and by the Italian Telethon Foundation grant to TIGEM 1996 – 1999.

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Authors and Affiliations

  1. Telethon Institute of Genetics and Medicine (TIGEM), San Raffaele Biomedical Science Park, Milan, 20132, Italy

    Alexandre Reymond, Sara Volorio, Giuseppe Merla, Alessandro Bulfone, Andrea Ballabio & Massimo Zollo

  2. Laboratorio di Citogenetica e Servizio di Genetica Medica, Ospedale San Raffaele, Milan, Italy

    Orsetta Zuffardi

  3. Ophthalmology Department of Molecular Genetics, Institute of Ophthalmology, University College London, London, UK

    Mai Al-Maghtheh

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  1. Alexandre Reymond
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Reymond, A., Volorio, S., Merla, G. et al. Evidence for interaction between human PRUNE and nm23-H1 NDPKinase. Oncogene 18, 7244–7252 (1999). https://doi.org/10.1038/sj.onc.1203140

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