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

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...

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Veröffentlicht in:Molecular and cellular biochemistry 2020-07, Vol.470 (1-2), p.63-75
Hauptverfasser: Perera, Yasser, Ramos, Yassel, Padrón, Gabriel, Caballero, Evelin, Guirola, Osmany, Caligiuri, Lorena G., Lorenzo, Norailys, Gottardo, Florencia, Farina, Hernán G., Filhol, Odile, Cochet, Claude, Perea, Silvio E.
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Sprache:eng
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Zusammenfassung: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.
ISSN:0300-8177
1573-4919
DOI:10.1007/s11010-020-03747-1