Neuroblastoma tumorigenesis is regulated through the Nm23-H1/h-Prune C-terminal interaction(507 views) Carotenuto M, Pedone E, Diana D, de Antonellis P, Džeroski S, Marino N, Navas L, Di Dato V, Scoppettuolo MN, Cimmino F, Correale S, Pirone L, Monti SM, Bruder E, Zenko B, Slavkov I, Pastorino F, Ponzoni M, Schulte JH, Schramm A, Eggert A, Westermann F, Arrigoni G, Accordi B, Basso G, Saviano M, Fattorusso R, Zollo M
Centro di Ingegneria Genetica e Biotecnologie Avanzate (CEINGE), Naples, Italy
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università 'Federico II' di Napoli, Italy
Istituto di Biostrutture e Bioimmagini, CNR, Napoli, Italy
Dipartimento di Scienze Ambientali, Seconda Università di Napoli, Caserta, Italy
Sezione di Clinica Chirurgica, Dipartimento di Scienze Cliniche Veterinarie, Università 'Federico II' di Napoli, Naples, Italy
Department of Pathology, University of Basel, Basel, Switzerland
Department of Knowledge Technologies, Jozief Stefan Institute, Jamova cesta 39, 1000 Ljubljana, Slovenia
Istituto Giannina Gaslini, Ospedale Pediatrico, 16148 Genoa, Italy
Department of Paediatric Oncology and Haematology, University Children's Hospital Essen, 45122 Essen, Germany
Department of Tumour Genetics, German Cancer Research Centre, Heidelberg, Germany
Haemato-Oncology Laboratory, Department of Paediatrics, University of Padova, Padua, Italy
Istituto di Cristallografia CNR, Bari, Italy
Women's Cancers Section, Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, United States
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Steeg, P. S., Zollo, M., Wieland, T., A critical evaluation of biochemical activities reported for the nucleoside diphosphate kinase/Nm23/Awd family proteins: Opportunities and missteps in understanding their biological functions (2011) Naunyn-Schmiedeberg's Archives of Pharmacology, 384, pp. 331-339
Godfried, M. B., Veenstra, M., Sluis, P. V., Boon, K., Asperen, R. V., Hermus, M. C., Schaik, B. D. C. V., Caron, H. N., The N-myc and c-myc downstream pathways include the chromosome 17q genes nm23-H1 and nm23-H2 (2002) Oncogene, 21 (13), pp. 2097-2101. , DOI 10. 1038/sj/onc/1205259
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Neuroblastoma tumorigenesis is regulated through the Nm23-H1/h-Prune C-terminal interaction
Nm23-H1 is one of the most interesting candidate genes for a relevant role in Neuroblastoma pathogenesis. H-Prune is the most characterized Nm23-H1 binding partner, and its overexpression has been shown in different human cancers. Our study focuses on the role of the Nm23-H1/h-Prune protein complex in Neuroblastoma. Using NMR spectroscopy, we performed a conformational analysis of the h-Prune C-terminal to identify the amino acids involved in the interaction with Nm23-H1. We developed a competitive permeable peptide (CPP) to impair the formation of the Nm23-H1/h-Prune complex and demonstrated that CPP causes impairment of cell motility, substantial impairment of tumor growth and metastases formation. Meta-analysis performed on three Neuroblastoma cohorts showed Nm23-H1 as the gene highly associated to Neuroblastoma aggressiveness. We also identified two other proteins (PTPRA and TRIM22) with expression levels significantly affected by CPP. These data suggest a new avenue for potential clinical application of CPP in Neuroblastoma treatment.
Neuroblastoma tumorigenesis is regulated through the Nm23-H1/h-Prune C-terminal interaction
Aloj L, Aurilio M, Rinaldi V, D'Ambrosio L, Tesauro D, Peitl PK, Maina T, Mansi R, Von Guggenberg E, Joosten L, Sosabowski JK, Breeman WA, De Blois E, Koelewijn S, Melis M, Waser B, Beetschen K, Reubi JC, De Jong M * The EEE project(449 views) Proc Int Cosm Ray Conf Icrc Universidad Nacional Autonoma De Mexico, 2007; 5(HEPART2): 977-980. Impact Factor:0 ViewExport to BibTeXExport to EndNote