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Casein kinase 2

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https://www.readbyqxmd.com/read/29214152/identification-of-candidate-casein-kinase-2-substrates-in-mitosis-by-quantitative-phosphoproteomics
#1
Scott F Rusin, Mark E Adamo, Arminja N Kettenbach
Protein phosphorylation is a crucial regulatory mechanism that controls many aspects of cellular signaling. Casein kinase 2 (CK2), a constitutively expressed and active kinase, plays key roles in an array of cellular events including transcription and translation, ribosome biogenesis, cell cycle progression, and apoptosis. CK2 is implicated in cancerous transformation and is a therapeutic target in anti-cancer therapy. The specific and selective CK2 ATP competitive inhibitor, CX-4945 (silmitaseratib), is currently in phase 2 clinical trials...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29182291/ru-ni-dual-catalytic-desulfinative-photoredox-csp2-csp3-cross-coupling-of-alkyl-sulfinate-salts-and-aryl-halides
#2
Thomas Knauber, Ramalakshmi Chandrasekaran, Joseph W Tucker, Jinshan Michael Chen, Matthew Reese, Danica A Rankic, Neal Sach, Christopher Helal
A mild Ru/Ni dual catalytic desulfinative photoredox Csp2-Csp3 cross-coupling reaction of alkyl sulfinate salts with aryl halides has been developed. The optimized catalyst system, consisting of Ru(bpy)3Cl2, Ni(COD)2, and DBU, smoothly mediates the coupling of a diverse set of secondary and primary nonactivated alkyl sulfinate salts with a broad range of electron-deficient aryl bromides, electron-rich aryl iodides, and heteroaryl bromides under irradiation with blue light. The procedure is ideal for late-stage introduction of alkyl groups on pharmaceutical intermediates, and the Csp2-Csp3 cross-coupling reaction allowed the rapid synthesis of caseine kinase 1δ inhibitor analogues via a parallel medicinal chemistry effort...
November 28, 2017: Organic Letters
https://www.readbyqxmd.com/read/29179493/sphingosine-kinase-1-mediates-diabetic-renal-fibrosis-via-nf-%C3%AE%C2%BAb-signaling-pathway-involvement-of-ck2%C3%AE
#3
Junying Huang, Jingyan Li, Zhiquan Chen, Jie Li, Qiuhong Chen, Wenyan Gong, Peiqing Liu, Heqing Huang
Sphingosine kinase 1 (SphK1) plays a pivotal role in regulating diabetic renal fibrotic factors such as fibronectin (FN) and intercellular adhesion molecule-1 (ICAM-1). Especially, activation of SphK1 is closely linked to the body inflammatory reaction. Casein kinase 2α subunit (CK2α), a protein kinase related to inflammatory reaction, influences diabetic renal fibrosis and expressions of FN and ICAM-1 via NF-κB pathway. However, the mechanism by which SphK1 mediates diabetic renal fibrosis has not yet fully elucidated...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151105/eryptosis-the-neglected-cause-of-anemia-in-end-stage-renal-disease
#4
Florian Lang, Rosi Bissinger, Majed Abed, Ferruh Artunc
End stage renal disease (ESRD) invariably leads to anemia which has been mainly attributed to compromised release of erythropoietin from the defective kidneys with subsequent impairment of erythropoiesis. However, erythropoietin replacement only partially reverses anemia pointing to the involvement of additional mechanisms. As shown more recently, anemia of ESRD is indeed in large part a result of accelerated erythrocyte loss due to suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the cell surface...
October 23, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29127314/modulation-of-transcriptional-mineralocorticoid-receptor-activity-by-casein-kinase-2
#5
Stefanie Ruhs, Nicole Strätz, Katja Quarch, Antonia Masch, Mike Schutkowski, Michael Gekle, Claudia Grossmann
The pathogenesis of cardiovascular diseases is a multifunctional process in which the mineralocorticoid receptor (MR), a ligand-dependent transcription factor, is involved as proven by numerous clinical studies. The development of pathophysiological MR actions depends on the existence of additional factors e.g. inflammatory cytokines and seems to involve posttranslational MR modifications e.g. phosphorylation. Casein kinase 2 (CK2) is a ubiquitously expressed multifunctional serine/threonine kinase that can be activated under inflammatory conditions as the MR...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29113166/expression-of-circadian-clock-genes-in-human-colorectal-adenoma-and-carcinoma
#6
Tomoyuki Momma, Hirokazu Okayama, Masaru Saitou, Hidekazu Sugeno, Nobuhiro Yoshimoto, Yuji Takebayashi, Shinji Ohki, Seiichi Takenoshita
Circadian rhythms are fundamental biological systems in most organisms. Epidemiological and animal studies have demonstrated that disruption of circadian rhythms is linked to tumor progression and mammalian tumorigenesis. However, the clinical significance of in situ clock gene expression in precancerous and cancerous colorectal lesions remains unknown. The present study aimed to investigate mRNA transcript levels of circadian clock genes within human colorectal cancer and adenoma tissue sections. Using in situ hybridization, the expression of key clock genes, including period circadian protein homolog (Per) 1 and 2, cryptochrome 1 (Cry1), circadian locomoter output cycles protein kaput (Clock), brain and muscle ARNT-like protein 1 (Bmal1) and casein kinase 1ε (CK1ε) were retrospectively examined in 51 cases of colorectal carcinoma and 10 cases of adenoma...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29107946/yeast-casein-kinase-2-governs-morphology-biofilm-formation-cell-wall-integrity-and-host-cell-damage-of-candida-albicans
#7
Sook-In Jung, Natalie Rodriguez, Jihyun Irrizary, Karl Liboro, Thania Bogarin, Marlene Macias, Edward Eivers, Edith Porter, Scott G Filler, Hyunsook Park
The regulatory networks governing morphogenesis of a pleomorphic fungus, Candida albicans are extremely complex and remain to be completely elucidated. This study investigated the function of C. albicans yeast casein kinase 2 (CaYck2p). The yck2Δ/yck2Δ strain displayed constitutive pseudohyphae in both yeast and hyphal growth conditions, and formed enhanced biofilm under non-biofilm inducing condition. This finding was further supported by gene expression analysis of the yck2Δ/yck2Δ strain which showed significant upregulation of UME6, a key transcriptional regulator of hyphal transition and biofilm formation, and cell wall protein genes ALS3, HWP1, and SUN41, all of which are associated with morphogenesis and biofilm architecture...
2017: PloS One
https://www.readbyqxmd.com/read/29097596/ck2-oppositely-modulates-l-dopa-induced-dyskinesia-via-striatal-projection-neurons-expressing-d1-or-d2-receptors
#8
Marisol Cortés, Lauren Malave, Julia Castello, Marc Flajolet, M Angela Cenci, Eitan Friedman, Heike Rebholz
We have previously shown that casein kinase 2 (CK2) negatively regulates dopamine D1- and adenosine A2a receptor signaling in the striatum. Ablation of CK2 in D1-receptor-positive striatal neurons caused enhanced locomotion and exploration at baseline, whereas CK2 ablation in D2 receptor-positive neurons caused increased locomotion after treatment with A2a antagonist, caffeine. Since both, D1 and A2a receptors, play major roles in the cellular responses to L-DOPA in the striatum, these findings prompted us to examine the impact of CK2 ablation on the effects of L-DOPA treatment in the unilateral 6-OHDA lesioned mouse model of Parkinson's disease...
November 2, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29069804/progesterone-receptor-membrane-component-1-is-phosphorylated-upon-progestin-treatment-in-breast-cancer-cells
#9
Marina Willibald, Giuliano Bayer, Vanessa Stahlhut, Gereon Poschmann, Kai Stühler, Berthold Gierke, Michael Pawlak, Harald Seeger, Alfred O Mueck, Dieter Niederacher, Tanja Fehm, Hans Neubauer
Menopausal hormone therapy, using estrogen and synthetic progestins, is associated with an increased risk of developing breast cancer. The effect of progestins on breast cells is complex and not yet fully understood. In previous in vitro and in vivo studies, we found different progestins to increase the proliferation of Progesterone Receptor Membrane Component-1 (PGRMC1)-overexpressing MCF7 cells (MCF7/PGRMC1), suggesting a possible role of PGRMC1 in transducing membrane-initiated progestin signals. Understanding the activation mechanism of PGRMC1 by progestins will provide deeper insights into the mode of action of progestins on breast cells and the often-reported phenomenon of elevated breast cancer rates upon progestin-based hormone therapy...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29044170/phosphorylation-regulates-the-subcellular-localization-of-cucumber-mosaic-virus-2b-protein
#10
Katalin Nemes, Ákos Gellért, Asztéria Almási, Pál Vági, Réka Sáray, Katalin Kádár, Katalin Salánki
The 2b protein of Cucumber mosaic virus has a role in nearly all steps of the viral cycle including cell-to-cell movement, symptom induction and suppression of antiviral RNA silencing. Previous studies demonstrated the presence of 2b protein in the nucleus and in cytoplasm as well. Phosphorylation site of 2b protein is conserved in all CMV isolates, including proposed constitute motifs for casein kinase II and cyclin-dependent kinase 2. To discern the impact of 2b protein phosphorylation, we created eight different mutants to mimic the non-phosporylated (serine to alanine) as well as the phosphorylated state (serine to aspartic acid) of the protein...
October 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29042609/structural-analysis-of-pim1-kinase-complexes-with-atp-competitive-inhibitors
#11
Jozefina Bogusz, Karol Zrubek, Krzysztof P Rembacz, Przemyslaw Grudnik, Przemyslaw Golik, Malgorzata Romanowska, Benedykt Wladyka, Grzegorz Dubin
PIM1 is an oncogenic kinase overexpressed in a number of cancers where it correlates with poor prognosis. Several studies demonstrated that inhibition of PIM1 activity is an attractive strategy in fighting overexpressing cancers, while distinct structural features of ATP binding pocket make PIM1 an inviting target for the design of selective inhibitors. To facilitate development of specific PIM1 inhibitors, in this study we report three crystal structures of ATP-competitive inhibitors at the ATP binding pocket of PIM1...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29033852/activation-of-casein-kinase-ii-by-gallic-acid-induces-bik-bax-bak-mediated-er-ca-ros-dependent-apoptosis-of-human-oral-cancer-cells
#12
Meng-Liang Lin, Shih-Shun Chen
Induction of the generation of endoplasmic reticulum (ER) calcium (Ca(++))-mediated reactive oxygen species (ROS) by gallic acid (GA) has been implicated in the mitochondrial apoptotic death of human oral cancer (OC) cells, but the molecular mechanism by which GA causes ER Ca(++) release of OC cells to undergo cell death remains unclear. Here, we report that GA-induced phosphorylation of B-cell lymphoma 2 (BCL-2)-interacting killer (BIK) (threonine (Thr) 33/Serine (Ser) 35) and p53 (Ser 15 and Ser 392), Bcl-2-associated x protein (BAX)/BCL-2 antagonist killer 1 (BAK) oligomerization on the ER and mitochondria, rising of cytosolic Ca(+)(+) and ROS, cytochrome c (Cyt c) release from the mitochondria, Ψm loss, and apoptosis were suppressed in cells co-treated with a specific inhibitor of casein kinase II (CK II) (4,5,6,7-tetrabromobenzotriazole)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29031723/inhibition-of-cholinergic-potentiation-of-insulin-secretion-from-pancreatic-islets-by-chronic-elevation-of-glucose-and-fatty-acids-protection-by-casein-kinase-2-inhibitor
#13
Nicolai M Doliba, Qin Liu, Changhong Li, Pan Chen, Chengyang Liu, Ali Naji, Franz M Matschinsky
OBJECTIVES: Chronic hyperlipidemia and hyperglycemia are characteristic features of type 2 diabetes (T2DM) that are thought to cause or contribute to β-cell dysfunction by "glucolipotoxicity." Previously we have shown that acute treatment of pancreatic islets with fatty acids (FA) decreases acetylcholine-potentiated insulin secretion. This acetylcholine response is mediated by M3 muscarinic receptors, which play a key role in regulating β-cell function. Here we examine whether chronic FA exposure also inhibits acetylcholine-potentiated insulin secretion using mouse and human islets...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29021227/physiological-regulation-of-the-epithelial-na-channel-by-casein-kinase-ii
#14
Jonathan M Berman, Elena Mironova, James D Stockand
The Epithelial Na+ Channel, ENaC, is the final arbiter of sodium excretion in the kidneys. As such, discretionary control of ENaC by hormones is critical to the fine-tuning of electrolyte and water excretion and consequently, blood pressure. Casein kinase 2 (CK2) phosphorylates ENaC. Phosphorylation by CK2 is necessary for normal ENaC activity. We tested the physiological importance of CK2 regulation of ENaC as the degree to which ENaC activity is dependent on CK2 phosphorylation in the living organism is unknown...
October 11, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28994305/plant-homeodomain-finger-protein-2-as-a-novel-ikaros-target-in-acute-lymphoblastic-leukemia
#15
Zheng Ge, Yan Gu, Qi Han, Justin Sloane, Qinyu Ge, Goufeng Gao, Jinlong Ma, Huihui Song, Jiaojiao Hu, Baoan Chen, Sinisa Dovat, Chunhua Song
AIM: Clinical significance of plant homeodomain finger 2 (PHF2) expressions is explored in acute lymphoblastic leukemia (ALL) patients. METHODS: mRNA level was examined by qPCR. The retroviral gene expression, shRNA knockdown and chromatin-immunoprecipitation are used to observe IKAROS regulation on PHF2 transcription. RESULTS: PHF2 expression is significantly reduced in subsets of ALL patients, and PHF2 (low) expression correlates with leukemia cell proliferation and an elevation of several poor prognostic markers in B-cell ALL...
October 10, 2017: Epigenomics
https://www.readbyqxmd.com/read/28993724/plpp-cin-regulates-seizure-activity-by-the-differential-modulation-of-calsenilin-binding-to-glun1-and-kv4-2-in-mice
#16
Ji-Eun Kim, Hye-Won Hyun, Su-Ji Min, Duk-Shin Lee, A Ran Jeon, Min Ju Kim, Tae-Cheon Kang
Calsenilin (CSEN) binds to Kv4.2 (an A-type K(+) channel) as well as N-methyl-D-aspartate receptor (NMDAR), and modulates their activities. However, the regulatory mechanisms for CSEN-binding to Kv4.2 or NMDAR remain elusive. Here, we demonstrate the novel role of pyridoxal-5'-phosphate phosphatase/chronophin (PLPP/CIN), one of the cofilin-mediated F-actin regulators, in the CSEN binding to Kv4.2 or GluN1 (an NMDAR subunit). PLPP/CIN dephosphorylated CSEN in competition with casein kinase 1, independent of cofilin dephosphorylation...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28993142/ghrelin-upregulates-the-phosphorylation-of-the-glun2b-subunit-of-the-nmda-receptor-by-activating-ghsr1a-and-fyn-in-the-rat-hippocampus
#17
Liza Berrout, Masako Isokawa
Ghrelin and its receptor GHSR1a have been shown to exert numerous physiological functions in the brain, in addition to the well-established orexigenic role in the hypothalamus. Earlier work indicated that ghrelin stimulated the phosphorylation of the GluN1 subunit of the NMDA receptor (NMDAR) and enhanced synaptic transmission in the hippocampus. In the present study, we report that the exogenous application of ghrelin increased GluN2B phosphorylation. This increase was independent of GluN2B subunit activity or NMDAR channel activity...
October 6, 2017: Brain Research
https://www.readbyqxmd.com/read/28992316/phosphorylation-of-cbx2-controls-its-nucleosome-binding-specificity
#18
Takayuki Kawaguchi, Shinichi Machida, Hitoshi Kurumizaka, Hideaki Tagami, Jun-Ichi Nakayama
Chromobox 2 (CBX2), a component of polycomb repressive complex 1 (PRC1), binds lysine 27-methylated histone H3 (H3K27me3) via its chromodomain (CD) and plays a critical role in repressing developmentally regulated genes. The phosphorylation of CBX2 has been described in several studies, but the biological implications of this modification remain largely elusive. Here, we show that CBX2's phosphorylation plays an important role in its nucleosome binding. CBX2 is stably phosphorylated in vivo, and domain analysis showed that residues in CBX2's serine-rich (SR) region are the predominant phosphorylation sites...
November 1, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28939766/casein-kinase-2-mediated-phosphorylation-of-brahma-related-gene-1-controls-myoblast-proliferation-and-contributes-to-swi-snf-complex-composition
#19
Teresita Padilla-Benavides, Brian T Nasipak, Amanda L Paskavitz, Dominic T Haokip, Jake M Schnabl, Jeffrey A Nickerson, Anthony N Imbalzano
Transcriptional regulation is modulated in part by chromatin-remodeling enzymes that control gene accessibility by altering chromatin compaction or nucleosome positioning. Brahma-related gene 1 (Brg1), a catalytic subunit of the mammalian SWI/SNF chromatin-remodeling enzymes, is required for both myoblast proliferation and differentiation, and the control of Brg1 phosphorylation by calcineurin, PKCβ1, and p38 regulates the transition to differentiation. However, we hypothesized that Brg1 activity might be regulated by additional kinases...
November 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28928952/a-simple-method-to-measure-clock-bmal1-dna-binding-activity-in-tissue-and-cell-extracts
#20
Maud Gillessen, Pieter Bas Kwak, Alfred Tamayo
The proteins CLOCK and BMAL1 form a heterodimeric transcription factor essential to circadian rhythms in mammals.  Daily rhythms of CLOCK-BMAL1 DNA binding activity are known to oscillate with target gene expression in vivo. Here we present a highly sensitive assay that recapitulates native CLOCK-BMAL1 DNA binding rhythms from crude tissue extracts, which we call the Clock Protein-DNA Binding Assay (CPDBA). This method can detect less than 2-fold differences in DNA binding activity, and can deliver results in two hours or less using 10 microliters or less of crude extract, while requiring neither specialized equipment nor expensive probes...
2017: F1000Research
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