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Mitsuhiro Yanagida - One of the best experts on this subject based on the ideXlab platform.

  • Casein Kinase II dependent phosphorylation of dna topoisomerase II suppresses the effect of a catalytic topo II inhibitor icrf 193 in fission yeast
    Journal of Biological Chemistry, 2019
    Co-Authors: Norihiko Nakazawa, Orie Arakawa, Mitsuhiro Yanagida
    Abstract:

    DNA topoisomerase II (topo II) regulates the topological state of DNA and is necessary for DNA replication, transcription, and chromosome segregation. Topo II has essential functions in cell proliferation and therefore is a critical target of anticancer drugs. In this study, using Phos-tag SDS-PAGE analysis in fission yeast (Schizosaccharomyces pombe), we identified Casein Kinase II (Cka1/CKII)–dependent phosphorylation at the C-terminal residues Ser1363 and Ser1364 in topo II. We found that this phosphorylation decreases the inhibitory effect of an anticancer catalytic inhibitor of topo II, ICRF-193, on mitosis. Consistent with the constitutive activity of Cka1/CKII, Ser1363 and Ser1364 phosphorylation of topo II was stably maintained throughout the cell cycle. We demonstrate that ICRF-193–induced chromosomal mis-segregation is further exacerbated in two temperature-sensitive mutants, cka1–372 and cka1/orb5-19, of the catalytic subunit of CKII or in the topo II nonphosphorylatable alanine double mutant top2-S1363A,S1364A but not in cells of the phosphomimetic glutamate double mutant top2-S1363E,S1364E. Our results suggest that Ser1363 and Ser1364 in topo II are targeted by Cka1/CKII Kinase and that their phosphorylation facilitates topo II ATPase activity in the N-terminal region, which regulates protein turnover on chromosome DNA. Because CKII-mediated phosphorylation of the topo II C-terminal domain appears to be evolutionarily conserved, including in humans, we propose that attenuation of CKII-controlled topo II phosphorylation along with catalytic topo II inhibition may promote anticancer effects.

  • Casein Kinase II–dependent phosphorylation of DNA topoisomerase II suppresses the effect of a catalytic topo II inhibitor, ICRF-193, in fission yeast
    'American Society for Biochemistry & Molecular Biology (ASBMB)', 2019
    Co-Authors: Norihiko Nakazawa, Orie Arakawa, Masahiro Ebe, Mitsuhiro Yanagida
    Abstract:

    DNA topoisomerase II (topo II) regulates the topological state of DNA and is necessary for DNA replication, transcription, and chromosome segregation. Topo II has essential functions in cell proliferation and therefore is a critical target of anticancer drugs. In this study, using Phos-tag SDS-PAGE analysis in fission yeast (Schizosaccharomyces pombe), we identified Casein Kinase II (Cka1/CKII)-dependent phosphorylation at the C-terminal residues Ser(1363) and Ser(1364) in topo II. We found that this phosphorylation decreases the inhibitory effect of an anticancer catalytic inhibitor of topo II, ICRF-193, on mitosis. Consistent with the constitutive activity of Cka1/CKII, Ser(1363) and Ser(1364) phosphorylation of topo II was stably maintained throughout the cell cycle. We demonstrate that ICRF-193-induced chromosomal mis-segregation is further exacerbated in two temperature-sensitive mutants, cka1-372 and cka1/orb5-19, of the catalytic subunit of CKII or in the topo II nonphosphorylatable alanine double mutant top2-S1363A,S1364A but not in cells of the phosphomimetic glutamate double mutant top2-S1363E,S1364E. Our results suggest that Ser(1363) and Ser(1364) in topo II are targeted by Cka1/CKII Kinase and that their phosphorylation facilitates topo II ATPase activity in the N-terminal region, which regulates protein turnover on chromosome DNA. Because CKII-mediated phosphorylation of the topo II C-terminal domain appears to be evolutionarily conserved, including in humans, we propose that attenuation of CKII-controlled topo II phosphorylation along with catalytic topo II inhibition may promote anticancer effects

Tarek Mohamed Abd Elaziz - One of the best experts on this subject based on the ideXlab platform.

  • mechanisms and consequences of Casein Kinase II and ankyrin 3 regulation of the epithelial na channel
    Scientific Reports, 2021
    Co-Authors: Tarek Mohamed Abd Elaziz, Antonio G Soares, Elena Mironova, Nina Boiko, Amanpreet Kaur, Crystal R Archer, James D Stockand, Jonathan M Berman
    Abstract:

    Activity of the Epithelial Na+ Channel (ENaC) in the distal nephron fine-tunes renal sodium excretion. Appropriate sodium excretion is a key factor in the regulation of blood pressure. Consequently, abnormalities in ENaC function can cause hypertension. Casein Kinase II (CKII) phosphorylates ENaC. The CKII phosphorylation site in ENaC resides within a canonical “anchor” ankyrin binding motif. CKII-dependent phosphorylation of ENaC is necessary and sufficient to increase channel activity and is thought to influence channel trafficking in a manner that increases activity. We test here the hypothesis that phosphorylation of ENaC by CKII within an anchor motif is necessary for ankyrin-3 (Ank-3) regulation of the channel, which is required for normal channel locale and function, and the proper regulation of renal sodium excretion. This was addressed using a fluorescence imaging strategy combining total internal reflection fluorescence (TIRF) microscopy with fluorescence recovery after photobleaching (FRAP) to quantify ENaC expression in the plasma membrane in living cells; and electrophysiology to quantify ENaC activity in split-open collecting ducts from principal cell-specific Ank-3 knockout mice. Sodium excretion studies also were performed in parallel in this knockout mouse. In addition, we substituted a key serine residue in the consensus CKII site in β-ENaC with alanine to abrogate phosphorylation and disrupt the anchor motif. Findings show that disrupting CKII signaling decreases ENaC activity by decreasing expression in the plasma membrane. In the principal cell-specific Ank-3 KO mouse, ENaC activity and sodium excretion were significantly decreased and increased, respectively. These results are consistent with CKII phosphorylation of ENaC functioning as a “switch” that favors Ank-3 binding to increase channel activity.

Jonathan M Berman - One of the best experts on this subject based on the ideXlab platform.

  • mechanisms and consequences of Casein Kinase II and ankyrin 3 regulation of the epithelial na channel
    Scientific Reports, 2021
    Co-Authors: Tarek Mohamed Abd Elaziz, Antonio G Soares, Elena Mironova, Nina Boiko, Amanpreet Kaur, Crystal R Archer, James D Stockand, Jonathan M Berman
    Abstract:

    Activity of the Epithelial Na+ Channel (ENaC) in the distal nephron fine-tunes renal sodium excretion. Appropriate sodium excretion is a key factor in the regulation of blood pressure. Consequently, abnormalities in ENaC function can cause hypertension. Casein Kinase II (CKII) phosphorylates ENaC. The CKII phosphorylation site in ENaC resides within a canonical “anchor” ankyrin binding motif. CKII-dependent phosphorylation of ENaC is necessary and sufficient to increase channel activity and is thought to influence channel trafficking in a manner that increases activity. We test here the hypothesis that phosphorylation of ENaC by CKII within an anchor motif is necessary for ankyrin-3 (Ank-3) regulation of the channel, which is required for normal channel locale and function, and the proper regulation of renal sodium excretion. This was addressed using a fluorescence imaging strategy combining total internal reflection fluorescence (TIRF) microscopy with fluorescence recovery after photobleaching (FRAP) to quantify ENaC expression in the plasma membrane in living cells; and electrophysiology to quantify ENaC activity in split-open collecting ducts from principal cell-specific Ank-3 knockout mice. Sodium excretion studies also were performed in parallel in this knockout mouse. In addition, we substituted a key serine residue in the consensus CKII site in β-ENaC with alanine to abrogate phosphorylation and disrupt the anchor motif. Findings show that disrupting CKII signaling decreases ENaC activity by decreasing expression in the plasma membrane. In the principal cell-specific Ank-3 KO mouse, ENaC activity and sodium excretion were significantly decreased and increased, respectively. These results are consistent with CKII phosphorylation of ENaC functioning as a “switch” that favors Ank-3 binding to increase channel activity.

  • Mechanisms and consequences of Casein Kinase II and ankyrin-3 regulation of the epithelial Na+ channel
    'Springer Science and Business Media LLC', 2021
    Co-Authors: Tarek Mohamed Abd El-aziz, Antonio G Soares, Elena Mironova, Nina Boiko, Amanpreet Kaur, Crystal R Archer, James D Stockand, Jonathan M Berman
    Abstract:

    Abstract Activity of the Epithelial Na+ Channel (ENaC) in the distal nephron fine-tunes renal sodium excretion. Appropriate sodium excretion is a key factor in the regulation of blood pressure. Consequently, abnormalities in ENaC function can cause hypertension. Casein Kinase II (CKII) phosphorylates ENaC. The CKII phosphorylation site in ENaC resides within a canonical “anchor” ankyrin binding motif. CKII-dependent phosphorylation of ENaC is necessary and sufficient to increase channel activity and is thought to influence channel trafficking in a manner that increases activity. We test here the hypothesis that phosphorylation of ENaC by CKII within an anchor motif is necessary for ankyrin-3 (Ank-3) regulation of the channel, which is required for normal channel locale and function, and the proper regulation of renal sodium excretion. This was addressed using a fluorescence imaging strategy combining total internal reflection fluorescence (TIRF) microscopy with fluorescence recovery after photobleaching (FRAP) to quantify ENaC expression in the plasma membrane in living cells; and electrophysiology to quantify ENaC activity in split-open collecting ducts from principal cell-specific Ank-3 knockout mice. Sodium excretion studies also were performed in parallel in this knockout mouse. In addition, we substituted a key serine residue in the consensus CKII site in β-ENaC with alanine to abrogate phosphorylation and disrupt the anchor motif. Findings show that disrupting CKII signaling decreases ENaC activity by decreasing expression in the plasma membrane. In the principal cell-specific Ank-3 KO mouse, ENaC activity and sodium excretion were significantly decreased and increased, respectively. These results are consistent with CKII phosphorylation of ENaC functioning as a “switch” that favors Ank-3 binding to increase channel activity

Norihiko Nakazawa - One of the best experts on this subject based on the ideXlab platform.

  • Casein Kinase II dependent phosphorylation of dna topoisomerase II suppresses the effect of a catalytic topo II inhibitor icrf 193 in fission yeast
    Journal of Biological Chemistry, 2019
    Co-Authors: Norihiko Nakazawa, Orie Arakawa, Mitsuhiro Yanagida
    Abstract:

    DNA topoisomerase II (topo II) regulates the topological state of DNA and is necessary for DNA replication, transcription, and chromosome segregation. Topo II has essential functions in cell proliferation and therefore is a critical target of anticancer drugs. In this study, using Phos-tag SDS-PAGE analysis in fission yeast (Schizosaccharomyces pombe), we identified Casein Kinase II (Cka1/CKII)–dependent phosphorylation at the C-terminal residues Ser1363 and Ser1364 in topo II. We found that this phosphorylation decreases the inhibitory effect of an anticancer catalytic inhibitor of topo II, ICRF-193, on mitosis. Consistent with the constitutive activity of Cka1/CKII, Ser1363 and Ser1364 phosphorylation of topo II was stably maintained throughout the cell cycle. We demonstrate that ICRF-193–induced chromosomal mis-segregation is further exacerbated in two temperature-sensitive mutants, cka1–372 and cka1/orb5-19, of the catalytic subunit of CKII or in the topo II nonphosphorylatable alanine double mutant top2-S1363A,S1364A but not in cells of the phosphomimetic glutamate double mutant top2-S1363E,S1364E. Our results suggest that Ser1363 and Ser1364 in topo II are targeted by Cka1/CKII Kinase and that their phosphorylation facilitates topo II ATPase activity in the N-terminal region, which regulates protein turnover on chromosome DNA. Because CKII-mediated phosphorylation of the topo II C-terminal domain appears to be evolutionarily conserved, including in humans, we propose that attenuation of CKII-controlled topo II phosphorylation along with catalytic topo II inhibition may promote anticancer effects.

  • Casein Kinase II–dependent phosphorylation of DNA topoisomerase II suppresses the effect of a catalytic topo II inhibitor, ICRF-193, in fission yeast
    'American Society for Biochemistry & Molecular Biology (ASBMB)', 2019
    Co-Authors: Norihiko Nakazawa, Orie Arakawa, Masahiro Ebe, Mitsuhiro Yanagida
    Abstract:

    DNA topoisomerase II (topo II) regulates the topological state of DNA and is necessary for DNA replication, transcription, and chromosome segregation. Topo II has essential functions in cell proliferation and therefore is a critical target of anticancer drugs. In this study, using Phos-tag SDS-PAGE analysis in fission yeast (Schizosaccharomyces pombe), we identified Casein Kinase II (Cka1/CKII)-dependent phosphorylation at the C-terminal residues Ser(1363) and Ser(1364) in topo II. We found that this phosphorylation decreases the inhibitory effect of an anticancer catalytic inhibitor of topo II, ICRF-193, on mitosis. Consistent with the constitutive activity of Cka1/CKII, Ser(1363) and Ser(1364) phosphorylation of topo II was stably maintained throughout the cell cycle. We demonstrate that ICRF-193-induced chromosomal mis-segregation is further exacerbated in two temperature-sensitive mutants, cka1-372 and cka1/orb5-19, of the catalytic subunit of CKII or in the topo II nonphosphorylatable alanine double mutant top2-S1363A,S1364A but not in cells of the phosphomimetic glutamate double mutant top2-S1363E,S1364E. Our results suggest that Ser(1363) and Ser(1364) in topo II are targeted by Cka1/CKII Kinase and that their phosphorylation facilitates topo II ATPase activity in the N-terminal region, which regulates protein turnover on chromosome DNA. Because CKII-mediated phosphorylation of the topo II C-terminal domain appears to be evolutionarily conserved, including in humans, we propose that attenuation of CKII-controlled topo II phosphorylation along with catalytic topo II inhibition may promote anticancer effects

S. Derek Killilea - One of the best experts on this subject based on the ideXlab platform.

  • hierarchical regulation by Casein Kinases i and II of the activation of protein phosphatase 1i by glycogen synthase Kinase 3 is ionic strength dependent
    Archives of Biochemistry and Biophysics, 1993
    Co-Authors: S P Henry, S. Derek Killilea
    Abstract:

    The roles of Casein Kinases I and II in the activation of protein phosphatase-1i (PP-1i) by glycogen synthase Kinase-3 (GSK-3) were studied using enzyme preparations from porcine heart. PP-1i was activated by GSK-3 and the levels of activation achieved decreased by increasing the ionic strength (0-0.2 M KCl) in the incubation mixtures. At low ionic strength (no KCl added) Casein Kinase II increased the rate of activation of PP-1i by GSK-3 and the activation proceeded to a slightly greater extent (110-120%) than that obtained by GSK-3 alone. In the presence of 0.14 M KCl only a partial activation of PP-1i by GSK-3 was observed, but when Casein Kinase II was also added activation was restored to levels observed when PP-1i was activated by GSK-3 in the absence of salt. This effect was shown to be dependent on the concentration of Casein Kinase II. These results would imply that at low ionic strength Casein Kinase II and GSK-3 synergistically activate PP-1i as has been previously reported for the rabbit skeletal muscle enzyme (DePaoli-Roach, A. A., J. Biol. Chem. 259, 12144-12152, 1984), whereas, at physiological ionic strength, Casein Kinase II action may be obligatory for GSK-3 activity. Similar results were obtained when Casein Kinase I replaced Casein Kinase II.