info:eu-repo/semantics/article
CIGB-300 anticancer peptide regulates the protein kinase CK2-dependent phosphoproteome
Fecha
2020-05-13Registro en:
Perera, Yasser; Ramos, Yassel; Padrón, Gabriel; Caballero, Evelin; Guirola, Osmany; et al.; CIGB-300 anticancer peptide regulates the protein kinase CK2-dependent phosphoproteome; Springer; Molecular and Cellular Biochemistry; 470; 1-2; 13-5-2020; 63-75
0300-8177
1573-4919
CONICET Digital
CONICET
Autor
Perera, Yasser
Ramos, Yassel
Padrón, Gabriel
Caballero, Evelin
Guirola, Osmany
Caligiuri, Lorena Gisel
Lorenzo Pérez, Norailys
Gottardo, María Florencia
Farina, Hernán Gabriel
Filhol, Odile
Cochet, Claude
Perea, Silvio E.
Resumen
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.