Targeting of Protein Kinase CK2 in Acute Myeloid Leukemia Cells Using the Clinical-Grade Synthetic-Peptide CIGB-300

نویسندگان

چکیده

Protein kinase CK2 has emerged as an attractive therapeutic target in acute myeloid leukemia (AML), advent that becomes particularly relevant since the treatment of this hematological neoplasia remains challenging. Here we explored for first time effect clinical-grade peptide-based inhibitor CIGB-300 on AML cells proliferation and viability. internalization subcellular distribution were also studied, role B23/nucleophosmin 1 (NPM1), a major peptide solid tumors, was addressed by knock-down model cell lines. Finally, pull-down experiments phosphoproteomic analysis performed to study CIGB-interacting proteins identify array substrates differentially modulated after with peptide. Importantly, elicited potent anti-proliferative proapoptotic cells, more than 80% transduced within three minutes. Unlike tumor NPM1 did not appear be cells. However, vivo evidenced targeted CK2α catalytic subunit, different ribosomal proteins, inhibited phosphorylation common among both backgrounds. Remarkably, our results only provide cellular molecular insights unveiling complexity anti-leukemic but reinforce rationale behind pharmacologic blockade protein AML-targeted therapy.

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ژورنال

عنوان ژورنال: Biomedicines

سال: 2021

ISSN: ['2227-9059']

DOI: https://doi.org/10.3390/biomedicines9070766