Inducible expression of the regulatory protein kinase CK2? subunit: Incorporation into complexes with catalytic CK2 subunits and re-examination of the effects of CK2? on cell proliferation

2001 ◽  
Vol 84 (1) ◽  
pp. 84-99 ◽  
Author(s):  
Greg Vilk ◽  
D. Richard Derksen ◽  
David W. Litchfield
Keyword(s):  
Cell Proliferation ◽  
Protein Kinase ◽  
Protein Kinase Ck2 ◽  
Regulatory Protein ◽  
Inducible Expression ◽  
Kinase Ck2

scholarly journals In Vitro and in Silico Evaluation of Bikaverin as a Potent Inhibitor of Human Protein Kinase CK2

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1380 ◽  
Author(s):  
Samer Haidar ◽  
Dagmar Aichele ◽  
Robin Birus ◽  
Janine Hielscher ◽  
Tuomo Laitinen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Kinase ◽  
Cell Viability ◽  
Binding Site ◽  
Protein Kinase Ck2 ◽  
Potent Inhibitor ◽  
Cell Permeability ◽  
Atp Binding Site ◽  
Kinase Ck2

Protein kinase CK2 is an emerging target for therapeutic intervention in human diseases, particularly in cancer. Inhibitors of this enzyme are currently in clinical trials, indicating the druggability of human CK2. By virtual screening of the ZINC database, we found that the natural compound bikaverin can fit well in the ATP binding site of the target enzyme CK2. By further in vitro evaluation using CK2 holoenzyme, bikaverin turned to be a potent inhibitor with an IC50 value of 1.24 µM. In this work, the cell permeability of bikaverin was determined using a Caco-2 cell permeability assay as a prerequisite for cellular evaluation and the compound turned out to be cell permeable with a Papp- value of 4.46 × 10−6 cm/s. Bikaverin was tested for its effect on cell viability using a MTT assay and cell proliferation using an EdU assay in different cancer cell lines (MCF7, A427 and A431 cells). Cell viability and cell proliferation were reduced dramatically after treatment with 10 µM bikaverin for 24 h. Additionally the IncuCyte® live-cell imaging system was applied for monitoring the cytotoxicity of bikaverin in the three tested cancer cell lines. Finally, molecular dynamic studies were performed to clarify the ligand binding mode of bikaverin at the ATP binding site of CK2 and to identify the amino acids involved.

scholarly journals Inducible Expression of Protein Kinase CK2 in Mammalian Cells

1999 ◽  
Vol 274 (20) ◽  
pp. 14406-14414 ◽  
Author(s):  
Greg Vilk ◽  
Ronald B. Saulnier ◽  
Rebecca St. Pierre ◽  
David W. Litchfield
Keyword(s):  
Protein Kinase ◽  
Mammalian Cells ◽  
Protein Kinase Ck2 ◽  
Inducible Expression ◽  
Kinase Ck2

scholarly journals Down-regulation of CK2α correlates with decreased expression levels of DNA replication minichromosome maintenance protein complex (MCM) genes

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Susanne Schaefer ◽  
Thomas K. Doktor ◽  
Sabrina B. Frederiksen ◽  
Kathleen Chea ◽  
Mirka Hlavacova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Dna Replication ◽  
Protein Kinase ◽  
Protein Kinase Ck2 ◽  
Minichromosome Maintenance ◽  
Catalytic Subunits ◽  
Expression Levels ◽  
Kinase Ck2

Abstract Protein kinase CK2 is a serine/threonine kinase composed of two catalytic subunits (CK2α and/or CK2α’) and two regulatory subunits (CK2β). It is implicated in every stage of the cell cycle and in the regulation of various intracellular pathways associated with health and disease states. The catalytic subunits have similar biochemical activity, however, their functions may differ significantly in cells and in vivo. In this regard, homozygous deletion of CK2α leads to embryonic lethality in mid-gestation potentially due to severely impaired cell proliferation. To determine the CK2α-dependent molecular mechanisms that control cell proliferation, we established a myoblast-derived cell line with inducible silencing of CK2α and carried out a comprehensive RNA-Seq analysis of gene expression. We report evidence that CK2α depletion causes delayed cell cycle progression through the S-phase and defective response to replication stress. Differential gene expression analysis revealed that the down-regulated genes were enriched in pathways implicated in cell cycle regulation, DNA replication and DNA damage repair. Interestingly, the genes coding for the minichromosome maintenance proteins (MCMs), which constitute the core of the replication origin recognition complex, were among the most significantly down-regulated genes. These findings were validated in cells and whole mouse embryos. Taken together, our study provides new evidence for a critical role of protein kinase CK2 in controlling DNA replication initiation and the expression levels of replicative DNA helicases, which ensure maintenance of proliferative potential and genome integrity in eukaryotic cells.

Cell cycle regulatory protein p27KIP1 is a substrate and interacts with the protein kinase CK2

2004 ◽  
Vol 91 (5) ◽  
pp. 865-879 ◽  
Author(s):  
Julio C. Tapia ◽  
Victor M. Bolanos-Garcia ◽  
Muhammed Sayed ◽  
Catherine C. Allende ◽  
Jorge E. Allende
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Protein Kinase Ck2 ◽  
Regulatory Protein ◽  
Cell Cycle Regulatory Protein ◽  
Kinase Ck2

Protein kinase CK2 phosphorylates the cell cycle regulatory protein Geminin

2004 ◽  
Vol 315 (4) ◽  
pp. 1011-1017 ◽  
Author(s):  
Monika Kulartz ◽  
Ekkehard Hiller ◽  
Ferdinand Kappes ◽  
Lorenzo A Pinna ◽  
Rolf Knippers
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Protein Kinase Ck2 ◽  
Regulatory Protein ◽  
Cell Cycle Regulatory Protein ◽  
Kinase Ck2
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