Casein kinase II is a negative regulator of c-Jun DNA binding and AP-1 activity

Summary statementThe conserved protein kinase CK2 negatively regulates centrosome assembly and is required for proper cell cycle progression and cytokinesis in early C. elegans embryos.AbstractCentrosomes are the primary microtubule-organizing centers that orchestrate microtubule dynamics during the cell cycle. The correct number of centrosomes is pivotal for establishing bipolar mitotic spindles that ensure accurate segregation of chromosomes. Thus, centrioles must duplicate once per cell cycle, one daughter per mother centriole, the process of which requires highly coordinated actions among core factors and modulators. Protein phosphorylation is shown to regulate the stability, localization and activity of centrosome proteins. Here, we report the function of Casein Kinase II (CK2) in early C. elegans embryos. The catalytic subunit (KIN-3/CK2α) of CK2 localizes to nuclei, centrosomes and midbodies. Inactivating CK2 leads to cell division defects, including chromosome missegregation, cytokinesis failure and aberrant centrosome behavior. Furthermore, depletion or inhibiting kinase activity of CK2 results in elevated ZYG-1 levels at centrosomes, restoring centrosome duplication and embryonic viability to zyg-1 mutants. Our data suggest that CK2 functions in cell division and negatively regulates centrosome duplication in a kinase-dependent manner.

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Casein kinase II inhibits the DNA-binding activity of Max homodimers but not Myc/Max heterodimers.

Genes & Development ◽

10.1101/gad.6.2.166 ◽

1992 ◽

Vol 6 (2) ◽

pp. 166-176 ◽

Cited By ~ 124

Author(s):

S J Berberich ◽

M D Cole

Keyword(s):

Dna Binding ◽

Casein Kinase Ii ◽

Binding Activity ◽

Casein Kinase ◽

Dna Binding Activity

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Phosphorylation of serine-167 on the human oestrogen receptor is important for oestrogen response element binding and transcriptional activation

Biochemical Journal ◽

10.1042/bj3260149 ◽

1997 ◽

Vol 326 (1) ◽

pp. 149-157 ◽

Cited By ~ 27

Author(s):

Enrique CASTAÑO ◽

Daria P. VOROJEIKINA ◽

Angelo C. NOTIDES

Keyword(s):

Dna Binding ◽

Transcriptional Activation ◽

Functional Significance ◽

Oestrogen Receptor ◽

Phosphorylation Site ◽

Casein Kinase Ii ◽

Casein Kinase ◽

Hormone Binding ◽

Dna Binding Affinity

We have studied the role of phosphorylation of the human oestrogen receptor (hOR; otherwise known as hER) at serine-167, which has been identified previously as the major oestrogen-induced phosphorylation site. We have tested transactivation by the hOR in yeast and cell-free transcription assays, and shown that mutation of serine-167 results in a 70% decrease in hOR-dependent transcription. Furthermore we explored the functional significance of phosphorylation at this site by hormone binding and DNA binding. DNA binding affinity was 10-fold lower when serine-167 was changed to alanine in the hOR. Cell-free transcription experiments showed that casein kinase II is the enzyme responsible for oestradiol-dependent phosphorylation of the hOR at serine-167. This suggests that a conformational change of the hOR must occur upon hormone binding that exposes serine-167 to casein kinase II, resulting in transactivation of oestrogen-responsive genes.

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Phosphorylation of the human estrogen receptor by mitogen-activated protein kinase and casein kinase II: Consequence on DNA binding

The Journal of Steroid Biochemistry and Molecular Biology ◽

10.1016/0960-0760(95)00177-2 ◽

1995 ◽

Vol 55 (2) ◽

pp. 163-172 ◽

Cited By ~ 76

Author(s):

Steven F. Arnold ◽

John D. Obourn ◽

Howard Jaffe ◽

Angelo C. Notides

Keyword(s):

Estrogen Receptor ◽

Protein Kinase ◽

Dna Binding ◽

Casein Kinase Ii ◽

Casein Kinase ◽

Mitogen Activated Protein Kinase ◽

Mitogen Activated Protein ◽

Human Estrogen Receptor

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Casein kinase II is required for proper cell division and acts as a negative regulator of centrosome duplication inCaenorhabditiselegansembryos

Biology Open ◽

10.1242/bio.022418 ◽

2016 ◽

Vol 6 (1) ◽

pp. 17-28 ◽

Cited By ~ 3

Author(s):

Jeffrey C. Medley ◽

Megan M. Kabara ◽

Michael D. Stubenvoll ◽

Lauren E. DeMeyer ◽

Mi Hye Song

Keyword(s):

Cell Division ◽

Casein Kinase Ii ◽

Casein Kinase ◽

Negative Regulator ◽

Centrosome Duplication

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Casein kinase II phosphorylation site mutations in c-Myb affect DNA binding and transcriptional cooperativity with NF-M.

Molecular and Cellular Biology ◽

10.1128/mcb.15.11.5966 ◽

1995 ◽

Vol 15 (11) ◽

pp. 5966-5974 ◽

Cited By ~ 50

Author(s):

M Oelgeschläger ◽

J Krieg ◽

J M Lüscher-Firzlaff ◽

B Lüscher

Keyword(s):

Dna Binding ◽

Phosphorylation Site ◽

Direct Interaction ◽

Casein Kinase Ii ◽

Casein Kinase ◽

Wild Type ◽

Type C ◽

A Site

Phosphorylation of c-Myb has been implicated in the regulation of the binding of c-Myb to DNA. We show that murine c-Myb is phosphorylated at Ser-11 and -12 in vivo and that these sites can be phosphorylated in vitro by casein kinase II (CKII), analogous to chicken c-Myb. An efficient method to study DNA binding properties of full-length c-Myb and Myb mutants under nondenaturing conditions was developed. It was found that a Myb mutant in which Ser-11 and -12 were replaced with Ala (Myb Ala-11/12), wild-type c-Myb, and Myb Asp-11/12 bound to the A site of the mim-1 promoter with decreasing affinities. In agreement with this finding, Myb Ala-11/12 transactivated better than wild-type c-Myb and Myb Asp-11/12 on the mim-1 promoter or a synthetic Myb-responsive promoter. Similar observations were made for the myeloid-specific neutrophil elastase promoter. The presence of NF-M or an NF-M-like activity abolished partially the differences seen with the Ser-11/12 mutants, suggesting that the reduced DNA binding due to negative charge at positions 11 and 12 can be compensated for by NF-M. Since no direct interaction of c-Myb and NF-M was observed, we propose that the cooperativity is mediated by a third factor. Our data offer two possibilities for how casein kinase II phosphorylation can influence c-Myb function: first, by reducing c-Myb DNA binding and thereby influencing transactivation, and second, by enhancing the apparent cooperativity between c-Myb and NF-M or an NF-M-like activity.

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