scholarly journals The catalytic subunit of Plasmodium falciparum casein kinase 2 is essential for gametocytogenesis

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Eva Hitz ◽  
Olivia Grüninger ◽  
Armin Passecker ◽  
Matthias Wyss ◽  
Christian Scheurer ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Sexual Development ◽  
Gene Editing ◽  
Stage Iv ◽  
Casein Kinase ◽  
Casein Kinase 2 ◽  
Catalytic Subunit ◽  
Blood Stage ◽  
Conditional Knockout ◽  
Cellular Compartments

AbstractCasein kinase 2 (CK2) is a pleiotropic kinase phosphorylating substrates in different cellular compartments in eukaryotes. In the malaria parasite Plasmodium falciparum, PfCK2 is vital for asexual proliferation of blood-stage parasites. Here, we applied CRISPR/Cas9-based gene editing to investigate the function of the PfCK2α catalytic subunit in gametocytes, the sexual forms of the parasite that are essential for malaria transmission. We show that PfCK2α localizes to the nucleus and cytoplasm in asexual and sexual parasites alike. Conditional knockdown of PfCK2α expression prevented the transition of stage IV into transmission-competent stage V gametocytes, whereas the conditional knockout of pfck2a completely blocked gametocyte maturation already at an earlier stage of sexual differentiation. In summary, our results demonstrate that PfCK2α is not only essential for asexual but also sexual development of P. falciparum blood-stage parasites and encourage studies exploring PfCK2α as a potential target for dual-active antimalarial drugs.

scholarly journals Full activation of a nuclear species of protein phosphatase-1 by phosphorylation with protein kinase A and casein kinase-2

1994 ◽  
Vol 297 (3) ◽  
pp. 447-449 ◽  
Author(s):  
A Van Eynde ◽  
M Beullens ◽  
W Stalmans ◽  
M Bollen
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Protein Phosphatase ◽  
Fold Increase ◽  
Casein Kinase ◽  
Casein Kinase 2 ◽  
Catalytic Subunit ◽  
Protein Phosphatase 1 ◽  
Nuclear Species ◽  
Kinase A

Bovine thymus nuclei contain a species of protein phosphatase-1 (PP-1N alpha) that can be partially activated by phosphorylation of an associated inhibitory polypeptide, NIPP-1, with protein kinase A [Beullens, Van Eynde, Bollen and Stalmans (1993) J. Biol. Chem. 268, 13172-13177]. Here it is shown that PP-1N alpha can also be activated 4-fold by phosphorylation of NIPP-1 with casein kinase-2. The effects of protein kinase A and casein kinase-2 were additive, yielding an enzyme with an activity close to that of the free catalytic subunit. Casein kinase-2 introduced up to 1.2 phosphate groups into purified NIPP-1 on serine and threonine residues. This phosphorylation was associated with a 14-fold increase in the concentration of NIPP-1 required for 50% inhibition of the type-1 catalytic subunit. The kinase-mediated inactivation of NIPP-1 could be reversed by incubation with the catalytic subunit of protein phosphatase-2A.

Translated Alu sequence determines nuclear localization of a novel catalytic subunit of casein kinase 2

2002 ◽  
Vol 283 (2) ◽  
pp. C472-C483 ◽  
Author(s):  
Philip Hilgard ◽  
Tianmin Huang ◽  
Allan W. Wolkoff ◽  
Richard J. Stockert
Keyword(s):  
Nuclear Localization ◽  
Nuclear Matrix ◽  
Fluorescent Protein ◽  
Hepatoma Cell ◽  
Casein Kinase ◽  
Casein Kinase 2 ◽  
Catalytic Subunit ◽  
Protein Fusion ◽  
Alu Sequence ◽  
Carboxy Terminal

Casein kinase 2 (CK2) is a tetrameric enzyme constitutively expressed in all eukaryotic tissues. The two known isoforms of the catalytic subunit, CK2α and CK2α′, have been reported to have distinct tissue-dependent subcellular distributions. We recently described a third isoform of the catalytic subunit, designated CK2α", which is highly expressed in liver. Immunoblot analysis of HuH-7 human hepatoma cell fractions as well as immunofluorescent microscopy revealed that CK2α" was exclusively localized to the nucleus and preferentially associated with the nuclear matrix. CK2α and CK2α′ were found in nuclear, membrane, and cytosolic compartments. Deletion of the carboxy-terminal 32 amino acids from the CK2α" sequence resulted in release of the truncated green fluorescent protein fusion protein from the nuclear matrix and redistribution to both the nucleus and the cytoplasm. Demonstration that the carboxy terminus is necessary but not sufficient for nuclear retention indicates that the underlying mechanism of CK2α" nuclear localization is dependent on the secondary structure of the holoenzyme directed by the carboxy-terminal sequence.

Statins as the Controlling Agents for Non-Hodgkin's Lymphomas via Increasing the Casein Kinase 2 Interacting Protein-1: A Hypothesis

2020 ◽  
Vol 17 (5) ◽  
pp. 616-618
Author(s):  
Kimia Kazemi ◽  
Negin Mozafari ◽  
Hajar Ashrafi ◽  
Pedram Rafiei ◽  
Amir Azadi
Keyword(s):  
Cell Proliferation ◽  
Mevalonate Pathway ◽  
Casein Kinase ◽  
Casein Kinase 2 ◽  
Interacting Protein ◽  
Akt Phosphorylation ◽  
Anticancer Properties ◽  
Proliferation And Apoptosis ◽  
Cellular Signaling Pathway ◽  
Hodgkin's Lymphomas

Background: Non-Hodgkin's lymphomas (NHL), derived from B- or T-cell, consist of a heterogeneous group of malignant lymphoproliferative disorders. Knockdown of Casein kinase 2 interacting protein-1 (CKIP-1) in NHL promoted cell proliferation and inhibited apoptosis via enhancing phosphorylated Protein Kinase B (PKB or AKT) expression. Statins are the class of drugs that inhibit the ratelimiting step of the mevalonate pathway, which is essential for the biosynthesis of various compounds, including cholesterol. Also, statins have anticancer properties being mediated by different mechanisms. Methods: A search on databases like Scopus and PubMed with keywords such as statin and non- Hodgkin's lymphomas was performed and Kyoto Encyclopedia of Genes and Genomes (KEGG) website was used to evaluate and reconfirm the involved cellular signaling pathway. Results: CKIP-1 is involved in the regulation of cell proliferation and apoptosis while plays an important role in many cancers. We can hypothesize that statins may increase the expression levels of CKIP-1 which could contribute to the reductions in phospho-AKT level. Hence, they may ameliorate the NHL patients via suppressing AKT phosphorylation and increasing CKIP- expression. Conclusion: Present review confirms the positive effect of statins on NHL by increasing CKIP-1 and reducing cell proliferation, subsequently.

Novel Anthraquinone Derivatives as Dual Inhibitors of Topoisomerase 2 and Casein Kinase 2: In Silico Studies, Synthesis and Biological Evaluation on Leukemic Cell Lines

2019 ◽  
Vol 18 (11) ◽  
pp. 1551-1562 ◽  
Author(s):  
Abbas Kabir ◽  
Kalpana Tilekar ◽  
Neha Upadhyay ◽  
C.S. Ramaa
Keyword(s):  
Cell Cycle ◽  
Cell Line ◽  
Cell Lines ◽  
Biological Evaluation ◽  
Casein Kinase ◽  
Casein Kinase 2 ◽  
Cell Cycle Analysis ◽  
Protein Targets ◽  
Topoisomerase 2 ◽  
Dual Inhibitors

Background: Cancer being a complex disease, single targeting agents remain unsuccessful. This calls for “multiple targeting”, wherein a single drug is so designed that it will modulate the activity of multiple protein targets. Topoisomerase 2 (Top2) helps in removing DNA tangles and super-coiling during cellular replication, Casein Kinase 2 (CK2) is involved in the phosphorylation of a multitude of protein targets. Thus, in the present work, we have tried to develop dual inhibitors of Top2 and CK2. Objective: With this view, in the present work, 2 human proteins, Top2 and CK2 have been targeted to achieve the anti-proliferative effects. Methods: Novel 1-acetylamidoanthraquinone (3a-3y) derivatives were designed, synthesized and their structures were elucidated by analytical and spectral characterization techniques (FTIR, 1H NMR, 13C NMR and Mass Spectroscopy). The synthesized compounds were then subjected to evaluation of cytotoxic potential by the Sulforhodamine B (SRB) protein assay, using HL60 and K562 cell lines. Ten compounds were analyzed for Top2, CK2 enzyme inhibitory potential. Further, top three compounds were subjected to cell cycle analysis. Results: The compounds 3a to 3c, 3e, 3f, 3i to 3p, 3t and 3x showed excellent cytotoxic activity to HL-60 cell line indicating their high anti-proliferative potential in AML. The compounds 3a to 3c, 3e, 3f, 3i to 3p and 3y have shown good to moderate activity on K-562 cell line. Compounds 3e, 3f, 3i, 3x and 3y were found more cytotoxic than standard doxorubicin. In cell cycle analysis, the cells (79-85%) were found to arrest in the G0/G1 phase. Conclusion: We have successfully designed, synthesized, purified and structurally characterized 1- acetylamidoanthraquinone derivatives. Even though our compounds need design optimization to further increase enzyme inhibition, their overall anti-proliferative effects were found to be encouraging.

scholarly journals Casein Kinase 2 dependent phosphorylation of eIF4B regulates BACE1 expression in Alzheimer’s disease

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Barbara Bettegazzi ◽  
Laura Sebastian Monasor ◽  
Serena Bellani ◽  
Franca Codazzi ◽  
Lisa Michelle Restelli ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Activity ◽  
Neurodegenerative Disorder ◽  
Brain Slices ◽  
Casein Kinase ◽  
Casein Kinase 2 ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Bace1 Expression

AbstractAlzheimer’s disease (AD) is the most common age-related neurodegenerative disorder. Increased Aβ production plays a fundamental role in the pathogenesis of the disease and BACE1, the protease that triggers the amyloidogenic processing of APP, is a key protein and a pharmacological target in AD. Changes in neuronal activity have been linked to BACE1 expression and Aβ generation, but the underlying mechanisms are still unclear. We provide clear evidence for the role of Casein Kinase 2 in the control of activity-driven BACE1 expression in cultured primary neurons, organotypic brain slices, and murine AD models. More specifically, we demonstrate that neuronal activity promotes Casein Kinase 2 dependent phosphorylation of the translation initiation factor eIF4B and this, in turn, controls BACE1 expression and APP processing. Finally, we show that eIF4B expression and phosphorylation are increased in the brain of APPPS1 and APP-KI mice, as well as in AD patients. Overall, we provide a definition of a mechanism linking brain activity with amyloid production and deposition, opening new perspectives from the therapeutic standpoint.

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