caa a22 4500 606233601 CHVBK 20210128101233.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s11010-015-2370-x doi (NATIONALLICENCE)springer-10.1007/s11010-015-2370-x Pharmacologic inhibition of the CK2-mediated phosphorylation of B23/NPM in cancer cells selectively modulates genes related to protein synthesis, energetic metabolism, and ribosomal biogenesis [Elektronische Daten] [Yasser Perera, Seidy Pedroso, Orlando Borras-Hidalgo, Dania Vázquez, Jamilet Miranda, Adelaida Villareal, Viviana Falcón, Luis Cruz, Hernán Farinas, Silvio Perea] B23/NPM is a multifunctional nucleolar protein frequently overexpressed, mutated, or rearranged in neoplastic tissues. B23/NPM is involved in diverse biological processes and is mainly regulated by heteroligomer association and posttranslational modification, phosphorylation being a major posttranslational event. While the role of B23/NPM in supporting and/or driving malignant transformation is widely recognized, the particular relevance of its CK2-mediated phosphorylation remains unsolved. Interestingly, the pharmacologic inhibition of such phosphorylation event by CIGB-300, a clinical-grade peptide drug, was previously associated to apoptosis induction in tumor cell lines. In this work, we sought to identify the biological processes modulated by CIGB-300 in a lung cancer cell line using subtractive suppression hybridization and subsequent functional annotation clustering. Our results indicate that CIGB-300 modulates a subset of genes involved in protein synthesis (ES=8.4, p<0.001), mitochondrial ATP metabolism (ES=2.5, p<0.001), and ribosomal biogenesis (ES=1.5, p<0.05). The impairment of these cellular processes by CIGB-300 was corroborated at the molecular and cellular levels by Western blot (P-S6/P-4EBP1, translation), confocal microscopy (JC-1, mitochondrial potential), qPCR (45SrRNA/p21, ribosome biogenesis), and electron microscopy (nucleolar structure, ribosome biogenesis). Altogether, our findings provide new insights on the potential relevance of the CK2-mediated phosphorylation of B23/NPM in cancer cells, revealing at the same time the potentialities of its pharmacological manipulation for cancer therapy. Finally, this work also suggests several candidate gene biomarkers to be evaluated during the clinical development of the anti-CK2 peptide CIGB-300. Springer Science+Business Media New York, 2015 B23/NPM nationallicence CK2 inhibitor nationallicence CIGB-300 nationallicence Nucleophosmin phosphorylation nationallicence Perera Yasser Laboratory of Molecular Oncology, Division of Pharmaceuticals, Center for Genetic Engineering and Biotechnology (CIGB), PO BOX 6162, CP10600, Havana, Cuba aut Pedroso Seidy Department of Genomics, Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba aut Borras-Hidalgo Orlando Plant Division, Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba aut Vázquez Dania Department of Genomics, Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba aut Miranda Jamilet Bioinformatics Department, Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba aut Villareal Adelaida Department of Genomics, Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba aut Falcón Viviana Chemical-Physical Division, Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba aut Cruz Luis Center for Advanced Studies of Cuba (CEAC), Carretera San Antonio, km 1-1/2, Puentes Grandes, Havana, Cuba aut Farinas Hernán Laboratory of Molecular Oncology, Quilmes National University, R. Sáenz Peña 352, Bernal B1876BXD, Buenos Aires, Argentina aut Perea Silvio Laboratory of Molecular Oncology, Division of Pharmaceuticals, Center for Genetic Engineering and Biotechnology (CIGB), PO BOX 6162, CP10600, Havana, Cuba aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 404/1-2(2015-06-01), 103-112 0300-8177 404:1-2<103 2015 404 11010 https://doi.org/10.1007/s11010-015-2370-x text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 brief-communication jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2370-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Perera Yasser Laboratory of Molecular Oncology, Division of Pharmaceuticals, Center for Genetic Engineering and Biotechnology (CIGB), PO BOX 6162, CP10600, Havana, Cuba aut NATIONALLICENCE 700 1- Pedroso Seidy Department of Genomics, Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba aut NATIONALLICENCE 700 1- Borras-Hidalgo Orlando Plant Division, Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba aut NATIONALLICENCE 700 1- Vázquez Dania Department of Genomics, Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba aut NATIONALLICENCE 700 1- Miranda Jamilet Bioinformatics Department, Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba aut NATIONALLICENCE 700 1- Villareal Adelaida Department of Genomics, Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba aut NATIONALLICENCE 700 1- Falcón Viviana Chemical-Physical Division, Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba aut NATIONALLICENCE 700 1- Cruz Luis Center for Advanced Studies of Cuba (CEAC), Carretera San Antonio, km 1-1/2, Puentes Grandes, Havana, Cuba aut NATIONALLICENCE 700 1- Farinas Hernán Laboratory of Molecular Oncology, Quilmes National University, R. Sáenz Peña 352, Bernal B1876BXD, Buenos Aires, Argentina aut NATIONALLICENCE 700 1- Perea Silvio Laboratory of Molecular Oncology, Division of Pharmaceuticals, Center for Genetic Engineering and Biotechnology (CIGB), PO BOX 6162, CP10600, Havana, Cuba aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 404/1-2(2015-06-01), 103-112 0300-8177 404:1-2<103 2015 404 11010