Disease relevance of Csnk2a2

• We find here that Csnk2a2 is preferentially expressed in late stages of spermatogenesis, and male mice in which Csnk2a2 has been disrupted are infertile, with oligospermia and globozoospermia ('round-headed' spermatozoa) [1].
• We find that CK2 is highly expressed in human breast tumor specimens and in carcinogen-induced rat mammary tumors [2].
• Transgenic mice overexpressing CK2alpha in the mammary gland develop mammary hyperplasia, dysplasia, and eventually adenocarcinomas, demonstrating that dysregulated expression of CK2 can contribute to transformation of the mammary epithelium [3].
• Induction of apoptosis by antisense CK2 in human prostate cancer xenograft model [4].
• Using the murine teratocarcinoma cell line F9 we investigated the influence of serum stimulation and cisplatin treatment on the p53, CK2, MDM2 levels [5].

High impact information on Csnk2a2

• Here we show that CK2 regulates PML protein levels by promoting its ubiquitin-mediated degradation dependent on direct phosphorylation at Ser517 [6].
• Importantly, we found an inverse correlation between CK2 kinase activity and PML protein levels in human lung cancer-derived cell lines and primary specimens [6].
• The Ck2alpha and Ck2alpha' isoforms (products of the genes Csnk2a1 and Csnk2a2, respectively) are highly homologous, but the reason for their redundancy and evolutionary conservation is unknown [1].
• The few that survive to populate the epididymis exhibit head abnormalities similar to those described in human globozoospermia, thus Csnk2a2 may be a candidate gene for these inherited syndromes [1].
• Impairment of AChR cluster formation after replacement of MuSK KI with KIs of other receptor tyrosine kinases correlates with potential CK2-dependent serine phosphorylation within KIs [7].

Chemical compound and disease context of Csnk2a2

• By contrast, chemical-induced apoptosis in prostate cancer and other cells (by etoposide and diethylstilbestrol) evokes an enhancement in CK2 associated with the NM that appears to be because of translocation of CK2 from the cytoplasmic to the nuclear compartment [8].
• Infection of Balb/MK cells with an ODC retrovirus to elevate ODC and polyamine levels increased overall protein phosphorylation as well as CK2 protein levels and enzyme activity in mimosine- or nocodazole- arrested cells [9].
• The extent of retinal neovascularization in a mouse OIR model was reduced >70% (versus untreated or vehicle-treated groups) after treatment with emodin (6 days at 60 mg/kg per day) and by approximately 60% after treatment at the same dose with TBB, the most specific CK2 inhibitor known [10].
• We have used whole-cell recording techniques in the mouse neuroblastoma X rat glioma hybrid NG108-15 cell line to test whether protein kinase CK2 (CK2; also known as casein kinase II) modulates the function of the serotonin 5-HT(3) receptor (5-HT(3)R) channel [11].

Biological context of Csnk2a2

• The NKX3.1 amino acid sequence includes multiple potential phosphoacceptor sites for protein kinase CK2 [12].
• We also show that p38 MAPK is able to directly associate with and modulate both casein kinase 2 (CK2) and protein kinase A (PKA), which promote and block APC nuclear import, respectively [13].
• Protein kinase CK2 is an ubiquitous and pleiotropic Ser/Thr protein kinase composed of two catalytic (alpha and/or alpha') and two noncatalytic (beta) subunits forming a heterotetrameric holoenzyme involved in cell growth and differentiation [14].
• The kinetics of CK2alpha' expression correlate with increased kinase activity toward a specific CK2 holoenzyme peptide substrate [14].
• Protein kinase CK2 is a ubiquitous and evolutionarily conserved serine/threonine kinase that is upregulated in many human cancers and can serve as an oncogene in lymphocytes [2].

Anatomical context of Csnk2a2

• Male mice in which Csnk2a2 has been disrupted were infertile and displayed oligozoospermia with an abnormal shape of the spermatid nucleus [15].
• In this study, Csnk2a2 null testes revealed extensive germ cell degenerative processes at all stages of spermatogenesis, including the first spermatogenesis wave [15].
• Previously, we purified a UV-responsive p53 serine 392 kinase from F9 and HeLa cells and found that its activity is attributed to a high molecular weight protein complex containing the protein kinase CK2, along with the chromatin-associated factors hSPT16 and SSRP1 [16].
• Protein kinase CK2 in mammary gland tumorigenesis [2].
• Recently, we have demonstrated that CK2 potentiates Wnt/beta-catenin signaling in mammary epithelial cells [2].

Associations of Csnk2a2 with chemical compounds

• Blocking CK2 activity in LNCaP cells with apigenin or 5,6-dichlorobenzimidazole riboside led to a rapid decrease in NKX3.1 accumulation that was rescued by proteasome inhibition [12].
• Arsenite also inhibited casein kinase 2 (CK2) activity and decreased p53-regulated p21 protein expression [17].
• Protein serine/threonine kinase CK2 (formerly casein kinase 2) is a ubiquitous protein kinase that plays key roles in cell growth, proliferation, and survival [4].
• The abilities of estradiol and a specific inhibitor of CK2 (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole) (DRB) to modulate the effects of TGF-beta1 on these processes were also examined [18].
• Determination of mRNA, and protein levels of p53, MDM2 and protein kinase CK2 subunits in F9 cells after treatment with the apoptosis-inducing drugs cisplatin and carboplatin [19].

Physical interactions of Csnk2a2

• Computer-assisted search was used to detect p53 consensus sequences in genes for CK2 subunits Binding of p53 protein to some of these sequences was assayed by electrophoretic mobility shift assay [20].

Enzymatic interactions of Csnk2a2

• Consistent with this finding, IFN-gamma stimulated CK2 activity and the level of phosphorylated cAMP response element-binding protein, which is known to induce ICER gene transcription, and this response was inhibited in the presence of apigenin [21].
• The tumor suppressor protein p53 is phosphorylated at a C-terminal residue (serine 386 in mouse p53) by the protein kinase CK2 [22].

Regulatory relationships of Csnk2a2

• We demonstrate that p38 MAPK is able to not only enhance CK2 kinase activity but also suppress PKA kinase activity [13].
• Phosphorylation by CK2 activates the specific DNA binding function of p53 and stimulates its ability to suppress cellular growth [22].

Other interactions of Csnk2a2

• Genomic DNA was extracted from peripheral blood and PCR was performed to amplify Csnk2a2 and Csnk2b genes before sequencing [23].
• We report that upon stable transfection of Wnt-1 into the mouse mammary epithelial cell line C57MG, morphological changes and increased proliferation are accompanied by increased levels of CK2, as well as of beta-catenin [24].
• 5: In addition, DRB (a pharmacological inhibitor of CK2) blocked TNF-alpha release in a concentration-dependent manner, whereas co-treatment of cells with luteolin and DRB did not have an additive effect [25].
• Experiments are underway to determine whether expression of both CK2 and kinase inactive GSK3 further accelerates tumorigenesis [26].
• The aim of this study was to determine if CK2 was affected by p53 [20].

Analytical, diagnostic and therapeutic context of Csnk2a2

• METHODS: Male Sprague-Dawley rats (200-250 g) were subjected to either partial hepatectomy or laparotomy and the levels and subcellular distribution of p53 were studied, following the approach used earlier for CK2 [20].
• We present direct evidence by immunoprecipitation for an association of protein kinase CK2 holoenzyme (alpha2beta2), p53, and the ribosomal protein L5 [5].
• Northern and Western blot analyses were performed and the CK2 activity was determined [19].
• A combination of segregation analysis of rodent-human hybrid cells and chromosomal in situ hybridization have localized the human CK II-alpha DNA sequence to two loci: 11p15.5-p15.4 and 20p13 [27].
• CK2 expression in human and rodent retinas with and without retinopathy and in astrocytic and endothelial cultures was examined by immunohistochemistry, Western blotting, and reverse transcriptase-polymerase chain reaction [28].

References