| Autor: |
Perera Y; China-Cuba Biotechnology Joint Innovation Center (CCBJIC), Yongzhou Zhong Gu Biotechnology Co., Ltd, Yangjiaqiao Street, Lengshuitan District, Yongzhou City, 425000, Hunan Province, China. yasserperera@outlook.com.; Molecular Oncology Group, Division of Pharmaceuticals, Center for Genetic Engineering & Biotechnology, Ave 31 e/158 & 190, Playa, 10600, Havana, Cuba. yasserperera@outlook.com., Ramos Y; Department of Proteomics. Biomedical Research Division, Center for Genetic Engineering & Biotechnology, Havana, Cuba., Padrón G; Department of Proteomics. Biomedical Research Division, Center for Genetic Engineering & Biotechnology, Havana, Cuba., Caballero E; Molecular Oncology Group, Division of Pharmaceuticals, Center for Genetic Engineering & Biotechnology, Ave 31 e/158 & 190, Playa, 10600, Havana, Cuba., Guirola O; Department of Proteomics. Biomedical Research Division, Center for Genetic Engineering & Biotechnology, Havana, Cuba., Caligiuri LG; Platform of Biotechnology Services, Quilmes National University, Roque Saenz Peña 352, 1876, Bernal, Buenos Aires, Argentina., Lorenzo N; Platform of Biotechnology Services, Quilmes National University, Roque Saenz Peña 352, 1876, Bernal, Buenos Aires, Argentina., Gottardo F; Platform of Biotechnology Services, Quilmes National University, Roque Saenz Peña 352, 1876, Bernal, Buenos Aires, Argentina., Farina HG; Platform of Biotechnology Services, Quilmes National University, Roque Saenz Peña 352, 1876, Bernal, Buenos Aires, Argentina., Filhol O; University of Grenoble Alpes, Inserm U1036, CEA, IRIG-BCI, 38000, Grenoble, France., Cochet C; University of Grenoble Alpes, Inserm U1036, CEA, IRIG-BCI, 38000, Grenoble, France., Perea SE; Molecular Oncology Group, Division of Pharmaceuticals, Center for Genetic Engineering & Biotechnology, Ave 31 e/158 & 190, Playa, 10600, Havana, Cuba. |
| Abstrakt: |
Casein-kinase CK2 is a Ser/Thr protein kinase that fosters cell survival and proliferation of malignant cells. The CK2 holoenzyme, formed by the association of two catalytic alpha/alpha' (CK2α/CK2α') and two regulatory beta subunits (CK2β), phosphorylates diverse intracellular proteins partaking in key cellular processes. A handful of such CK2 substrates have been identified as targets for the substrate-binding anticancer peptide CIGB-300. However, since CK2β also contains a CK2 phosphorylation consensus motif, this peptide may also directly impinge on CK2 enzymatic activity, thus globally modifying the CK2-dependent phosphoproteome. To address such a possibility, firstly, we evaluated the potential interaction of CIGB-300 with CK2 subunits, both in cell-free assays and cellular lysates, as well as its effect on CK2 enzymatic activity. Then, we performed a phosphoproteomic survey focusing on early inhibitory events triggered by CIGB-300 and identified those CK2 substrates significantly inhibited along with disturbed cellular processes. Altogether, we provided here the first evidence for a direct impairment of CK2 enzymatic activity by CIGB-300. Of note, both CK2-mediated inhibitory mechanisms of this anticancer peptide (i.e., substrate- and enzyme-binding mechanism) may run in parallel in tumor cells and help to explain the different anti-neoplastic effects exerted by CIGB-300 in preclinical cancer models. |
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