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

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.

• Authors: Yasser Perera, Yassel Ramos, Gabriel Padrón, Evelin Caballero, Osmany Guirola, Lorena G Caligiuri, Norailys Lorenzo, Florencia Gottardo, Hernán G Farina, Odile Filhol, Claude Cochet, Silvio E Perea
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 470 Issue 1-2 Pg. 63-75 (Jul 2020) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 32405972 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Peptides, Cyclic
• Proteome
• Recombinant Proteins
• Casein Kinase II
• CIGB-300

Topics

• Antineoplastic Agents (pharmacology)
• Carcinoma, Non-Small-Cell Lung (metabolism)
• Casein Kinase II (metabolism)
• Catalytic Domain
• Cell Line, Tumor
• Cell-Free System
• Gene Expression Regulation, Neoplastic
• Humans
• Lung Neoplasms (metabolism)
• Microscopy, Fluorescence
• Peptides, Cyclic (pharmacology)
• Phosphorylation
• Protein Binding
• Proteome
• Recombinant Proteins (metabolism)