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CIGB-300 anticancer peptide regulates the protein kinase CK2-dependent phosphoproteome

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Abstract

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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Funding

This work was conducted with the financial support of the CIGB-300 Grant, Biomedical Research Division, CIGB, Cuba.

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Authors and Affiliations

  1. China-Cuba Biotechnology Joint Innovation Center (CCBJIC), Yongzhou Zhong Gu Biotechnology Co., Ltd, Yangjiaqiao Street, Lengshuitan District, Yongzhou City, 425000, Hunan Province, China

    Yasser Perera

  2. Molecular Oncology Group, Division of Pharmaceuticals, Center for Genetic Engineering & Biotechnology, Ave 31 e/158 & 190, Playa, 10600, Havana, Cuba

    Yasser Perera, Evelin Caballero & Silvio E. Perea

  3. Department of Proteomics. Biomedical Research Division, Center for Genetic Engineering & Biotechnology, Havana, Cuba

    Yassel Ramos, Gabriel Padrón & Osmany Guirola

  4. Platform of Biotechnology Services, Quilmes National University, Roque Saenz Peña 352, 1876, Bernal, Buenos Aires, Argentina

    Lorena G. Caligiuri, Norailys Lorenzo, Florencia Gottardo & Hernán G. Farina

  5. University of Grenoble Alpes, Inserm U1036, CEA, IRIG-BCI, 38000, Grenoble, France

    Odile Filhol & Claude Cochet

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  1. Yasser Perera
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Correspondence to Yasser Perera.

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Perera, Y., Ramos, Y., Padrón, G. et al. CIGB-300 anticancer peptide regulates the protein kinase CK2-dependent phosphoproteome. Mol Cell Biochem 470, 63–75 (2020). https://doi.org/10.1007/s11010-020-03747-1

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