| 2009 |
CK2α phosphorylates the circadian regulator BMAL1 at Ser90; gene silencing of CK2α or mutation of Ser90 impairs nuclear BMAL1 accumulation and disrupts circadian clock function, and phosphorylation at Ser90 follows a rhythmic pattern. |
Gene silencing (siRNA), site-directed mutagenesis, phosphorylation assays, nuclear localization assays |
Nature structural & molecular biology |
High |
19330005
|
| 2007 |
Dominant-negative CK2α (CK2αTik) in Drosophila clock neurons reduces PER phosphorylation, delays nuclear entry of PER, dampens PER cycling, and prolongs circadian period (~33 h), establishing CK2α as a key regulator of PER negative feedback timing. |
Transgenic dominant-negative expression in circadian neurons, behavioral rhythmicity assay, immunostaining for PER phosphorylation and nuclear localization |
PLoS genetics |
High |
18208335
|
| 2011 |
Crystal structure of human CK2α' determined at 2 Å resolution. CK2α' has ~12-fold lower affinity for CK2β than CK2α (Kd ~150 nM vs ~13 nM), driven less by enthalpy. The β4/β5 loop in CK2α' adopts an open conformation stabilized by an N-terminal β-strand extension and a tryptophan filling a conserved hydrophobic cavity, features absent in CK2α. |
X-ray crystallography, isothermal titration calorimetry (ITC), Michaelis-Menten kinetics |
Journal of molecular biology |
High |
21241709
|
| 2003 |
Disruption of Csnk2a2 (CK2α') in male mice causes infertility and oligozoospermia with spermatid nuclear abnormalities, nuclear envelope protrusions, loss of nuclear pores, and extensive germ cell death at all spermatogenic stages, indicating CK2α' is required for phosphorylation of nuclear proteins in male germ cells. |
Gene knockout in mice, histology, electron microscopy, fluorescent DNA staining |
Molecular reproduction and development |
High |
12950107
|
| 2013 |
CK2α' (CSNK2A2) exhibits a striking isoform-specific preference for phosphorylating caspase-3 in cells compared to CK2α, and CK2β abolishes caspase-3 phosphorylation; caspase-3 is the first substrate selectively phosphorylated by CK2α' in cells. |
Modulation of individual CK2 subunit expression (siRNA knockdown and overexpression), cell-based phosphorylation assays |
Oncotarget |
Medium |
23599180
|
| 2016 |
CK2α' phosphorylates nuclear BRMS1 at Ser30 in response to TNF, causing 14-3-3ε-mediated nuclear export and ubiquitin-proteasome degradation of BRMS1, thereby promoting lung cancer metastasis; S30 mutation or CK2 inhibitor CX4945 abrogates this effect and reduces metastasis ~60-fold in vivo. |
In vitro kinase assay, site-directed mutagenesis (S30A), orthotopic mouse metastasis model, co-immunoprecipitation, siRNA, small-molecule inhibitor |
Cancer research |
High |
26980766
|
| 2009 |
CK2α is phosphorylated at four sites during mitosis (maximally in prophase/metaphase) and dephosphorylated during anaphase/telophase; phosphomimetic CK2α (4D/4E) causes centrosome amplification, chromosomal segregation defects, and mitotic catastrophe, while non-phosphorylatable CK2α (4A) impairs the spindle assembly checkpoint response. |
Phosphospecific antibodies, stable expression of phosphomimetic and non-phosphorylatable mutants, immunofluorescence, nocodazole treatment/release |
Molecular and cellular biology |
High |
19188443
|
| 2011 |
Phosphorylated CK2α localizes to the mitotic spindle in a phosphorylation-dependent manner requiring the unique C-terminus of CK2α; this localization requires binding to the peptidyl-prolyl isomerase Pin1, which is facilitated by CK2α phosphorylation. |
Phosphospecific antibodies, immunofluorescence, co-immunoprecipitation, deletion mutants |
Journal of cell science |
High |
21693590
|
| 1998 |
CK2α' mRNA is induced by serum as a delayed early gene in quiescent fibroblasts (peaks at 4 h); ectopic CK2α' cooperates with Ha-ras in foci formation and fibroblast transformation, correlating with increased calmodulin phosphorylation—a substrate specific to free CK2 catalytic subunits rather than holoenzyme. |
Northern blot, kinase activity assay toward CK2 peptide substrate and calmodulin, foci formation assay in primary rat embryo fibroblasts |
The Journal of biological chemistry |
High |
9694889
|
| 1998 |
CK2α associates physically with c-Abl and with the Bcr-Abl fusion protein; Bcr-Abl phosphorylates CK2α on tyrosine, inhibiting its kinase activity, and this inhibition is reversed by tyrosine phosphatase treatment. |
Anti-phosphotyrosine immunoblotting, immunoprecipitation, in vitro kinase assay, tyrosine phosphatase treatment |
Oncogene |
Medium |
9671309
|
| 2008 |
CK2α and CK2β interact with a dissociation constant of 12.6 nM, driven predominantly by enthalpic rather than entropic contributions; CK2β requires a preformed conformation for interaction, while CK2α undergoes significant backbone structural adaptations upon assembly. |
Isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC), X-ray crystallography of CK2β |
Protein science |
High |
18824508
|
| 2007 |
Crystal structure of fully active C-terminal deletion mutant of human CK2α at 1.6 Å with two bound sulfate ions; sulfate anions occupy the activation segment and the +1 loop binding pockets, providing structural basis for the acidic consensus substrate recognition sequence S/T-D/E-X-D/E; CK2α lacks phosphorylatable residues at the activation segment, making it constitutively active. |
X-ray crystallography (1.6 Å), structural comparison with CMGC kinases |
Journal of molecular biology |
High |
17524418
|
| 2004 |
CK2α interacts with MKP3 (MAP kinase phosphatase 3) forming a protein complex that can include ERK2; CK2α selectively phosphorylates MKP3, slightly increasing MKP3 phosphatase activity in vitro but reducing ERK2 dephosphorylation in transfected cells. |
Yeast two-hybrid, co-immunoprecipitation, in vitro phosphatase assay, transfection |
The Journal of biological chemistry |
Medium |
15284227
|
| 2003 |
eIF2β directly binds both CK2α (high affinity) and CK2β (low affinity) as measured by surface plasmon resonance; free CK2α cannot phosphorylate eIF2β but reconstituted CK2 holoenzyme phosphorylates eIF2β (~1.2 mol phosphate/mol); eIF2β inhibits CK2α activity on calmodulin and β-casein but has minimal effect on holoenzyme activity. |
Surface plasmon resonance, co-immunoprecipitation, in vitro kinase assay with reconstituted holoenzyme |
The Biochemical journal |
High |
12901717
|
| 2006 |
BID is a substrate and binding partner of CK2α; CK2α (but not holoenzyme unless stimulated by polylysine) phosphorylates BID at Thr58 and Ser76; phosphorylation of BID by CK2α prior to caspase-8 cleavage reduces formation of truncated BID (tC-BID); BID co-immunoprecipitates preferentially with CK2α subunit. |
In vitro kinase assay, co-immunoprecipitation, mass spectrometry, enzyme kinetics |
Biological chemistry |
Medium |
16606343
|
| 2009 |
KIF5C (a kinesin motor neuron protein) is a direct binding partner of CK2α' with a preference over CK2α; interaction confirmed by co-sedimentation on sucrose gradient, co-immunoprecipitation, pull-down, and surface plasmon resonance; co-localization observed in neuroblastoma cells and primary neurons. |
Yeast two-hybrid, co-sedimentation, co-immunoprecipitation, pull-down, surface plasmon resonance, co-localization by immunofluorescence |
Cellular and molecular life sciences |
High |
19011756
|
| 2016 |
CK2α (CSNK2A1) phosphorylates SIRT6 and physically associates with it; phosphorylation of SIRT6 at Ser338 by CK2α promotes cancer cell proliferation and invasiveness, and mutation at Ser338 inhibits proliferation and decreases MMP9, β-catenin, cyclin D1, and NF-κB expression. |
Co-immunoprecipitation, GST pull-down assay, in vitro kinase assay, dominant-negative CK2α transfection, SIRT6 Ser338Ala mutant |
The American journal of pathology |
High |
27746184
|
| 2011 |
CK2α phosphorylates the transcription factor YY1 at Ser118 in vitro and in vivo; CK2α inhibition or knockdown reduces Ser118 phosphorylation and enhances YY1 cleavage by caspase 7 during apoptosis; Ser118Ala mutation also increases YY1 cleavage, linking CK2α phosphorylation to protection of YY1 from caspase-mediated cleavage. |
In vitro kinase assay, siRNA knockdown, CK2α overexpression, site-directed mutagenesis (S118A), apoptosis assay |
Molecular and cellular biology |
High |
22184066
|
| 2003 |
The PK60S kinase from S. cerevisiae 60S ribosomes, which phosphorylates ribosomal P-proteins, was identified as the CK2α' catalytic subunit by peptide mass fingerprinting; CK2α' activity is inhibited by SOD1 (superoxide dismutase), forming an inactive complex. |
Protein purification, peptide mass fingerprinting (PMF), kinase activity assay, inhibition by SOD1 |
Biochemical and biophysical research communications |
Medium |
12849977
|
| 1999 |
CK2α forms a molecular complex with protein phosphatase 2A (PP2A) core dimer; expression of activated Raf disrupts this CK2α-PP2A association; CK2α overexpression inhibits mitogen-induced MAP kinase activation in a dose-dependent manner. |
Transfection, immune kinase assays, co-immunoprecipitation |
Molecular and cellular biochemistry |
Medium |
10094410
|
| 2016 |
CK2α maintains ERK phosphorylation in BRAF-mutant melanoma through two mechanisms: (1) kinase-dependent post-translational downregulation of the ERK phosphatase DUSP6, and (2) kinase-independent scaffolding via binding to KSR1 (a RAF-MEK-ERK scaffold), with both wild-type and kinase-inactive CK2α binding KSR1 equally. |
CK2α overexpression/knockdown, kinase-inactive mutant expression, co-immunoprecipitation with KSR1, Western blot for ERK phosphorylation and DUSP6, ERK inhibitor comparison |
The Journal of biological chemistry |
High |
27226552
|
| 2017 |
CK2α phosphorylates BMI1 at Ser110; preventing this phosphorylation significantly decreases BMI1 half-life and stability; phosphorylatable but not non-phosphorylatable BMI1 rescues clonal growth in BMI1-silenced cancer cells. |
Immunoprecipitation, in vitro and ex vivo kinase assay, mass spectrometry, siRNA, overexpression of phosphorylation mutants, stability assay |
Molecular cancer |
High |
28270146
|
| 2013 |
CK2α is a positive regulator of Hedgehog/Gli signaling in lung cancer cells; CK2α silencing reduces Gli1 expression and transcriptional activity; forced CK2α overexpression increases Gli1 transcriptional activity; CK2α inhibition reduces the cancer stem-like side population with elevated ABCG2. |
siRNA knockdown, forced overexpression, luciferase reporter assay, RT-PCR, small-molecule CK2α inhibitors |
PloS one |
Medium |
22768056
|
| 2018 |
CK2α phosphorylates FUNDC1 at Ser13, inactivating FUNDC1-mediated mitophagy; cardiac-specific CK2α knockout preserves mitophagy and protects against IR injury; mice doubly deficient in CK2α and FUNDC1 lose the protective effect, confirming epistasis. |
Cardiac-specific CK2α knockout mice, double knockout (CK2α + FUNDC1), phosphorylation assays, mitophagy functional assays |
Cell death and differentiation |
Medium |
29540794
|
| 2018 |
NR4A1 activates CK2α, which then phosphorylates Mff to promote Drp1-dependent mitochondrial fission and phosphorylates FUNDC1 to inhibit mitophagy, together driving endothelial apoptosis in microvascular IR injury. |
NR4A1 knockout mice, siRNA, phosphorylation assays, Drp1 translocation assay, mitophagy assay |
Basic research in cardiology |
Medium |
29744594
|
| 2016 |
A novel binding site on CK2α adjacent to the ATP site (αD pocket) was identified; a bivalent inhibitor (CAM4066, Kd = 320 nM) anchored in this αD pocket linked to a fragment in the ATP site inhibits CK2α with improved selectivity and shows cellular target engagement. |
Fragment-based drug discovery, X-ray crystallography, ITC, cell viability assays |
Chemical science |
High |
28451126
|
| 2011 |
Dual knockout of both CK2α and CK2α' catalytic subunits (by CRISPR/Cas9) promotes accelerated proteasomal degradation of the CK2β regulatory subunit and causes rearrangement of the proteome with >240 proteins altered >50% in level. |
CRISPR/Cas9 gene editing, quantitative proteomics, proteasome inhibitor treatment |
Scientific reports |
High |
28209983
|
| 2013 |
In an ES cell-based circadian assay, homozygous CK2α mutant ES cells show ~2.5-hour longer circadian periods after differentiation, providing genetic evidence for an essential role of CK2α in the mammalian circadian clock. |
Homozygous CK2α mutant ES cells, in vitro differentiation, circadian reporter assay, revertant cell line confirmation |
PloS one |
High |
23840637
|
| 2001 |
The C-terminal domain of grp94 protects CK2α against thermal aggregation (but not thermal inactivation) in a concentration-dependent manner; disulfide bonds stabilizing grp94 oligomers are required for this chaperone activity. |
In vitro aggregation assay, DTT reduction, concentration-response analysis |
European journal of biochemistry |
Medium |
11168379
|
| 2010 |
Structure-guided alanine scanning of the CK2α/CK2β interface identified Leu41 and Phe54 on CK2α as the dominant affinity-determining residues; Ile69 despite its central position contributes modestly; Leu41 and Phe54 mutations are not additive, indicating cooperative action. CK2α mutants retained kinase activity. |
ITC, alanine scanning mutagenesis, kinase activity assay |
Biochemistry |
High |
21142136
|
| 2019 |
CK2α is required for HPV replication (HPV11, HPV18) in a kinase activity-dependent manner; CK2α regulates stability and nuclear retention of E1 replication proteins of HPV11 and HPV18; CK2α' knockdown does not affect HPV replication, demonstrating isoform specificity. |
siRNA knockdown of CK2α vs CK2α', HPV replication assays with marker genomes, CX4945 inhibitor, nuclear retention assays |
PLoS pathogens |
High |
31091289
|
| 2002 |
The carboxyl-terminal residues 324–328 of CK2α (Xenopus) are essential for catalytic activity; deletion of these residues reduces activity 7000-fold; key residues are Ile327 and Phe324 in helix αN, whose hydrophobic interactions with helix αE (linked to the catalytic center) are required for activity. |
Deletion mutagenesis, recombinant CK2α kinase activity assay, 3D structural modeling |
FEBS letters |
High |
12417343
|
| 2021 |
Fifteen different OCNDS-linked missense mutations in CSNK2A1 (CK2α) lead to varying degrees of reduced kinase activity; some variants also show altered subcellular localization; patient-derived fibroblasts show changes in the phosphoproteome. |
Recombinant protein kinase activity assay, ectopic expression in mammalian cells, phosphoproteomics, immunofluorescence localization |
Human genetics |
High |
33944995
|
| 2022 |
The OCNDS-associated CK2α Lys198Arg mutation shifts the anion binding site at the P+1 loop (key element of substrate recognition) without affecting CK2β interaction or thermal stability, leading to altered substrate specificity confirmed by enzymological assays. |
X-ray crystallography, ITC, differential scanning fluorimetry, fluorescence quenching, in vitro kinase assay |
Frontiers in molecular biosciences |
High |
35445078
|
| 2021 |
A N-terminally deleted form of CK2α' (deleted upstream of Glu-15) is sufficient to support cell viability in CK2α/α'-/- cells; this truncated form co-immunoprecipitates with CK2β and is downregulated by CK2α'-specific siRNA, demonstrating the N-terminal segment regulates CK2α' activity and stability. |
CRISPR/Cas9 knockout, siRNA, co-immunoprecipitation, in-gel kinase assay, SDS-PAGE |
Biochemical and biophysical research communications |
Medium |
32800562
|
| 2018 |
CK2α interacts with Jak2 and induces phosphorylation and activation of Jak2-Stat3; Stat3 then directly binds the Opa1 promoter to upregulate Opa1 transcription and mitochondrial fusion; CK2α knockdown blunts Jak2-Stat3 phosphorylation and Opa1-mediated fusion. |
Molecular docking, siRNA knockdown, chromatin immunoprecipitation, pharmacological screening, Western blot |
Redox biology |
Medium |
34418601
|
| 2024 |
CK2α phosphorylates GRP94 at Ser306, increasing GRP94 stability and enhancing its interaction with LRP6, leading to activation of canonical Wnt signaling and TNBC metastasis. |
In vitro kinase assay, phosphorylation site identification, co-immunoprecipitation, LRP6 interaction assay, CK2α inhibitor (benzamidine), in vivo metastasis model |
Cell death discovery |
Medium |
38649679
|
| 2018 |
CK2α phosphorylates Mff (mitochondrial fission factor), promoting Drp1 cytoplasmic-to-mitochondrial translocation and mitochondrial fission in cardiac microvascular IR injury. |
siRNA, phosphorylation assay, Drp1 translocation assay, mitochondrial morphology analysis |
Basic research in cardiology |
Medium |
29744594
|