CK2 and the Hallmarks of Cancer

Biomedicines, Journal Year: 2022, Volume and Issue: 10(8), P. 1987 - 1987

Published: Aug. 16, 2022

Cancer is a leading cause of death worldwide. Casein kinase 2 (CK2) commonly dysregulated in cancer, impacting diverse molecular pathways. CK2 highly conserved serine/threonine kinase, constitutively active and ubiquitously expressed eukaryotes. With over 500 known substrates being estimated to be responsible for up 10% the human phosphoproteome, it significant importance. A broad spectrum types cancer cells has been already shown rely on disturbed levels their survival. The hallmarks provide rationale understanding cancer's common traits. They constitute maintenance proliferative signaling, evasion growth suppressors, resisting cell death, enabling replicative immortality, induction angiogenesis, activation invasion metastasis, as well avoidance immune destruction dysregulation cellular energetics. In this work, we have compiled evidence from literature suggesting that modulates all thereby promoting oncogenesis operating driver by creating environment favorable neoplasia.

Language: Английский

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In silico investigations identified Butyl Xanalterate to competently target CK2α (CSNK2A1) for therapy of chronic lymphocytic leukemia

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: Oct. 21, 2022

Abstract Chronic lymphocytic leukemia (CLL) is an incurable malignancy of B-cells. In this study, bioinformatics analyses were conducted to identify possible pathogenic roles CK2α, which a protein encoded by CSNK2A1 , in the progression and aggressiveness CLL. Furthermore, various computational tools used search for competent inhibitor CK2α from fungal metabolites that could be proposed CLL therapy. patients, high-expression was associated with early need therapy (n = 130, p < 0.0001) short overall survival (OS; n 107, 0.005). Consistently, showed associate with/play proliferation survival-dependent pathways. PPI network analysis identified interaction partners (PPI enrichment value 1 × 10 –16 ) 0.003) have been known heavily impact on These findings constructed rational targeting Consequently, reported 35 out 5820 (filtered 19,967 metabolites) lower binding energy (ΔG: − 10.9 11.7 kcal/mol) better affinity (Kd: 9.77 7 M −1 3.77 8 compared native ligand 10.8, Kd: 8.3 M− ). molecular dynamics simulation study established Butyl Xanalterate-CK2α complex continuously remained stable throughout time (100 ns). Moreover, Xanalterate interacted most catalytic residues, where stabilized more than 65% hydrogen bond interactions, significant hydrophobic residue Phe113. Here, implicated poor prognosis CLL, making it potential therapeutic target disease. strong interactions thus we propose as competitive

Language: Английский

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A PARylation-phosphorylation cascade promotes TOPBP1 loading and RPA-RAD51 exchange in homologous recombination

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(14), P. 2571 - 2587.e9

Published: May 20, 2022

Language: Английский

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Host Kinase CSNK2 is a Target for Inhibition of Pathogenic SARS-like β-Coronaviruses

ACS Chemical Biology, Journal Year: 2022, Volume and Issue: 17(7), P. 1937 - 1950

Published: June 19, 2022

Inhibition of the protein kinase CSNK2 with any 30 specific and selective inhibitors representing different chemotypes, blocked replication pathogenic human, bat, murine β-coronaviruses. The potency in-cell CSNK2A target engagement across set correlated antiviral activity genetic knockdown confirmed essential role holoenzyme in β-coronavirus replication. Spike endocytosis was by inhibition, indicating that due part to a suppression viral entry. inhibition may be viable for development anti-SARS-like drugs.

Language: Английский

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The Role of Protein Kinase CK2 in Development and Disease Progression: A Critical Review

Journal of Developmental Biology, Journal Year: 2022, Volume and Issue: 10(3), P. 31 - 31

Published: July 27, 2022

Protein kinase CK2 (CK2) is a ubiquitous holoenzyme involved in wide array of developmental processes. The involvement events such as neurogenesis, cardiogenesis, skeletogenesis, and spermatogenesis essential for the viability almost all organisms, its role has been conserved throughout evolution. Further into adulthood, continues to function key regulator pathways affecting crucial processes osteogenesis, adipogenesis, chondrogenesis, neuron differentiation, immune response. Due vast multitude pathways, aberrant functioning this leads embryonic lethality numerous diseases disorders, including cancer neurological disorders. As result, popular target interventions aiming treat aforementioned diseases. Specifically, two inhibitors, namely CX-4945 CIBG-300, are early stages clinical testing exhibit promise treating other Further, researchers around world focusing on bone This review summarizes current understanding development, structure CK2, targets signaling implication disease progression, recent therapeutics developed inhibit dysregulation various

Language: Английский

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