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

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 posttransl...

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Autores: Perera, Yasser, Pedroso, Seidy, Borras-Hidalgo, Orlando, Vázquez, Dania M., Miranda, Jamilet, Villareal, Adelaida, Falcón, Viviana, Cruz, Luis D., Farina, Hernán Gabriel, Perea, Silvio E.
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2015
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositório:CONICET Digital (CONICET)
Idioma:inglês
OAI Identifier:oai:ri.conicet.gov.ar:11336/38362
Acesso em linha:http://hdl.handle.net/11336/38362
Access Level:Acceso aberto
Palavra-chave:B23/Npm
Cigb-300
Ck2 Inhibitor
Nucleophosmin Phosphorylation
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
id AR_2ffa2dfe2cdc67a2f1e34c7baf52c11c
oai_identifier_str oai:ri.conicet.gov.ar:11336/38362
network_acronym_str AR
network_name_str Argentina
repository_id_str
dc.title.none.fl_str_mv 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
title 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
spellingShingle 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
Perera, Yasser
B23/Npm
Cigb-300
Ck2 Inhibitor
Nucleophosmin Phosphorylation
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
dc.creator.none.fl_str_mv Perera, Yasser
Pedroso, Seidy
Borras-Hidalgo, Orlando
Vázquez, Dania M.
Miranda, Jamilet
Villareal, Adelaida
Falcón, Viviana
Cruz, Luis D.
Farina, Hernán Gabriel
Perea, Silvio E.
author Perera, Yasser
author_facet Perera, Yasser
Pedroso, Seidy
Borras-Hidalgo, Orlando
Vázquez, Dania M.
Miranda, Jamilet
Villareal, Adelaida
Falcón, Viviana
Cruz, Luis D.
Farina, Hernán Gabriel
Perea, Silvio E.
author_role author
author2 Pedroso, Seidy
Borras-Hidalgo, Orlando
Vázquez, Dania M.
Miranda, Jamilet
Villareal, Adelaida
Falcón, Viviana
Cruz, Luis D.
Farina, Hernán Gabriel
Perea, Silvio E.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv B23/Npm
Cigb-300
Ck2 Inhibitor
Nucleophosmin Phosphorylation
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
topic B23/Npm
Cigb-300
Ck2 Inhibitor
Nucleophosmin Phosphorylation
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
description 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.
publishDate 2015
dc.date.none.fl_str_mv 2015-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/38362
Perera, Yasser; Pedroso, Seidy; Borras-Hidalgo, Orlando; Vázquez, Dania M.; Miranda, Jamilet; et al.; 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; Springer; Molecular and Cellular Biochemistry; 404; 1-2; 6-2015; 103-112
0300-8177
1573-4919
CONICET Digital
CONICET
url http://hdl.handle.net/11336/38362
identifier_str_mv Perera, Yasser; Pedroso, Seidy; Borras-Hidalgo, Orlando; Vázquez, Dania M.; Miranda, Jamilet; et al.; 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; Springer; Molecular and Cellular Biochemistry; 404; 1-2; 6-2015; 103-112
0300-8177
1573-4919
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs11010-015-2370-x
info:eu-repo/semantics/altIdentifier/doi/10.1007/s11010-015-2370-x
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1799196418728001536
spelling Pharmacologic inhibition of the CK2-mediated phosphorylation of B23/NPM in cancer cells selectively modulates genes related to protein synthesis, energetic metabolism, and ribosomal biogenesisPerera, YasserPedroso, SeidyBorras-Hidalgo, OrlandoVázquez, Dania M.Miranda, JamiletVillareal, AdelaidaFalcón, VivianaCruz, Luis D.Farina, Hernán GabrielPerea, Silvio E.B23/NpmCigb-300Ck2 InhibitorNucleophosmin Phosphorylationhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1B23/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.Fil: Perera, Yasser. Centro de Ingeniería Genética y Biotecnología; CubaFil: Pedroso, Seidy. Centro de Ingeniería Genética y Biotecnología; CubaFil: Borras-Hidalgo, Orlando. Centro de Ingeniería Genética y Biotecnología; CubaFil: Vázquez, Dania M.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Miranda, Jamilet. Centro de Ingeniería Genética y Biotecnología; CubaFil: Villareal, Adelaida. Centro de Ingeniería Genética y Biotecnología; CubaFil: Falcón, Viviana. Centro de Ingeniería Genética y Biotecnología; CubaFil: Cruz, Luis D.. Centro de Estudios Avanzados de Cuba; CubaFil: Farina, Hernán Gabriel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Perea, Silvio E.. Centro de Ingeniería Genética y Biotecnología; CubaSpringer2015-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/38362Perera, Yasser; Pedroso, Seidy; Borras-Hidalgo, Orlando; Vázquez, Dania M.; Miranda, Jamilet; et al.; 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; Springer; Molecular and Cellular Biochemistry; 404; 1-2; 6-2015; 103-1120300-81771573-4919CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs11010-015-2370-xinfo:eu-repo/semantics/altIdentifier/doi/10.1007/s11010-015-2370-xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T14:26:56Zoai:ri.conicet.gov.ar:11336/38362instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982024-05-08 14:26:56.809CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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