Phosphoproteomic Landscape of AML Cells Treated with the ATP-Competitive CK2 Inhibitor CX-4945

Casein kinase 2 (CK2) regulates a plethora of proteins with pivotal roles in solid and hematological neoplasia. Particularly, in acute myeloid leukemia (AML) CK2 has been pointed as an attractive therapeutic target and prognostic marker. Here, we explored the impact of CK2 inhibition over the phosph...

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Main Authors: Mauro Rosales, Arielis Rodríguez-Ulloa, Vladimir Besada, Ailyn C. Ramón, George V. Pérez, Yassel Ramos, Osmany Guirola, Luis J. González, Katharina Zettl, Jacek R. Wiśniewski, Yasser Perera, Silvio E. Perea
Format: Article
Language:English
Published: MDPI AG 2021-02-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/10/2/338
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spelling doaj-e6d424a0b5734fff9b1b6d91708f0af12021-02-06T00:05:06ZengMDPI AGCells2073-44092021-02-011033833810.3390/cells10020338Phosphoproteomic Landscape of AML Cells Treated with the ATP-Competitive CK2 Inhibitor CX-4945Mauro Rosales0Arielis Rodríguez-Ulloa1Vladimir Besada2Ailyn C. Ramón3George V. Pérez4Yassel Ramos5Osmany Guirola6Luis J. González7Katharina Zettl8Jacek R. Wiśniewski9Yasser Perera10Silvio E. Perea11Department of Animal and Human Biology, Faculty of Biology, University of Havana (UH), Havana 10400, CubaMass Spectrometry Laboratory, Proteomics Group, Department of Systems Biology, Biomedical Research Division, CIGB, Havana 10600, CubaMass Spectrometry Laboratory, Proteomics Group, Department of Systems Biology, Biomedical Research Division, CIGB, Havana 10600, CubaMolecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering and Biotechnology (CIGB), Havana 10600, CubaMolecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering and Biotechnology (CIGB), Havana 10600, CubaMass Spectrometry Laboratory, Proteomics Group, Department of Systems Biology, Biomedical Research Division, CIGB, Havana 10600, CubaBioinformatics Group, Department of Systems Biology, Biomedical Research Division, CIGB, Havana 10600, CubaMass Spectrometry Laboratory, Proteomics Group, Department of Systems Biology, Biomedical Research Division, CIGB, Havana 10600, CubaBiochemical Proteomics Group, Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, 82152 Munich, GermanyBiochemical Proteomics Group, Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, 82152 Munich, GermanyMolecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering and Biotechnology (CIGB), Havana 10600, CubaMolecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering and Biotechnology (CIGB), Havana 10600, CubaCasein kinase 2 (CK2) regulates a plethora of proteins with pivotal roles in solid and hematological neoplasia. Particularly, in acute myeloid leukemia (AML) CK2 has been pointed as an attractive therapeutic target and prognostic marker. Here, we explored the impact of CK2 inhibition over the phosphoproteome of two cell lines representing major AML subtypes. Quantitative phosphoproteomic analysis was conducted to evaluate changes in phosphorylation levels after incubation with the ATP-competitive CK2 inhibitor CX-4945. Functional enrichment, network analysis, and database mining were performed to identify biological processes, signaling pathways, and CK2 substrates that are responsive to CX-4945. A total of 273 and 1310 phosphopeptides were found differentially modulated in HL-60 and OCI-AML3 cells, respectively. Despite regulated phosphopeptides belong to proteins involved in multiple biological processes and signaling pathways, most of these perturbations can be explain by direct CK2 inhibition rather than off-target effects. Furthermore, CK2 substrates regulated by CX-4945 are mainly related to mRNA processing, translation, DNA repair, and cell cycle. Overall, we evidenced that CK2 inhibitor CX-4945 impinge on mediators of signaling pathways and biological processes essential for primary AML cells survival and chemosensitivity, reinforcing the rationale behind the pharmacologic blockade of protein kinase CK2 for AML targeted therapy.https://www.mdpi.com/2073-4409/10/2/338phosphoproteomicscasein kinase 2kinase inhibitorCX-4945acute myeloid leukemia
collection DOAJ
language English
format Article
sources DOAJ
author Mauro Rosales
Arielis Rodríguez-Ulloa
Vladimir Besada
Ailyn C. Ramón
George V. Pérez
Yassel Ramos
Osmany Guirola
Luis J. González
Katharina Zettl
Jacek R. Wiśniewski
Yasser Perera
Silvio E. Perea
spellingShingle Mauro Rosales
Arielis Rodríguez-Ulloa
Vladimir Besada
Ailyn C. Ramón
George V. Pérez
Yassel Ramos
Osmany Guirola
Luis J. González
Katharina Zettl
Jacek R. Wiśniewski
Yasser Perera
Silvio E. Perea
Phosphoproteomic Landscape of AML Cells Treated with the ATP-Competitive CK2 Inhibitor CX-4945
Cells
phosphoproteomics
casein kinase 2
kinase inhibitor
CX-4945
acute myeloid leukemia
author_facet Mauro Rosales
Arielis Rodríguez-Ulloa
Vladimir Besada
Ailyn C. Ramón
George V. Pérez
Yassel Ramos
Osmany Guirola
Luis J. González
Katharina Zettl
Jacek R. Wiśniewski
Yasser Perera
Silvio E. Perea
author_sort Mauro Rosales
title Phosphoproteomic Landscape of AML Cells Treated with the ATP-Competitive CK2 Inhibitor CX-4945
title_short Phosphoproteomic Landscape of AML Cells Treated with the ATP-Competitive CK2 Inhibitor CX-4945
title_full Phosphoproteomic Landscape of AML Cells Treated with the ATP-Competitive CK2 Inhibitor CX-4945
title_fullStr Phosphoproteomic Landscape of AML Cells Treated with the ATP-Competitive CK2 Inhibitor CX-4945
title_full_unstemmed Phosphoproteomic Landscape of AML Cells Treated with the ATP-Competitive CK2 Inhibitor CX-4945
title_sort phosphoproteomic landscape of aml cells treated with the atp-competitive ck2 inhibitor cx-4945
publisher MDPI AG
series Cells
issn 2073-4409
publishDate 2021-02-01
description Casein kinase 2 (CK2) regulates a plethora of proteins with pivotal roles in solid and hematological neoplasia. Particularly, in acute myeloid leukemia (AML) CK2 has been pointed as an attractive therapeutic target and prognostic marker. Here, we explored the impact of CK2 inhibition over the phosphoproteome of two cell lines representing major AML subtypes. Quantitative phosphoproteomic analysis was conducted to evaluate changes in phosphorylation levels after incubation with the ATP-competitive CK2 inhibitor CX-4945. Functional enrichment, network analysis, and database mining were performed to identify biological processes, signaling pathways, and CK2 substrates that are responsive to CX-4945. A total of 273 and 1310 phosphopeptides were found differentially modulated in HL-60 and OCI-AML3 cells, respectively. Despite regulated phosphopeptides belong to proteins involved in multiple biological processes and signaling pathways, most of these perturbations can be explain by direct CK2 inhibition rather than off-target effects. Furthermore, CK2 substrates regulated by CX-4945 are mainly related to mRNA processing, translation, DNA repair, and cell cycle. Overall, we evidenced that CK2 inhibitor CX-4945 impinge on mediators of signaling pathways and biological processes essential for primary AML cells survival and chemosensitivity, reinforcing the rationale behind the pharmacologic blockade of protein kinase CK2 for AML targeted therapy.
topic phosphoproteomics
casein kinase 2
kinase inhibitor
CX-4945
acute myeloid leukemia
url https://www.mdpi.com/2073-4409/10/2/338
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