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https://www.readbyqxmd.com/read/29127314/modulation-of-transcriptional-mineralocorticoid-receptor-activity-by-casein-kinase-2
#1
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/29124793/evidence-for-allosteric-effects-on-p53-oligomerization-induced-by-phosphorylation
#2
Petr Muller, Juliana M Chan, Oliver Simoncik, Miroslav Fojta, David P Lane, Ted Hupp, Borivoj Vojtesek
P53 is a tetrameric protein with a thermodynamically unstable DNA-binding domain flanked by intrinsically disordered regulatory domains that control its activity. The unstable and disordered segments of p53 allow high flexibility as it interacts with binding partners and permits a rapid on/off switch to control its function. The p53 tetramer can exist in multiple conformational states, any of which can be stabilized by a particular modification. Here, we apply the allostery model to p53 to ask whether evidence can be found that the "activating" C-terminal phosphorylation of p53 stabilizes a specific conformation of the protein in the absence of DNA...
November 10, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29119230/re-evaluation-of-protein-kinase-ck2-pleiotropy-new-insights-provided-by-a-phosphoproteomics-analysis-of-ck2-knockout-cells
#3
Cinzia Franchin, Christian Borgo, Luca Cesaro, Silvia Zaramella, Jordi Vilardell, Mauro Salvi, Giorgio Arrigoni, Lorenzo A Pinna
CK2 denotes a ubiquitous and pleiotropic protein kinase whose holoenzyme is composed of two catalytic (α and/or α') and two regulatory β subunits. The CK2 consensus sequence, S/T-x-x-D/E/pS/pT is present in numerous phosphosites, but it is not clear how many of these are really generated by CK2. To gain information about this issue, advantage has been taken of C2C12 cells entirely deprived of both CK2 catalytic subunits by the CRISPR/Cas9 methodology. A comparative SILAC phosphoproteomics analysis reveals that, although about 30% of the quantified phosphosites do conform to the CK2 consensus, only one-third of these are substantially reduced in the CK2α/α'((-/-)) cells, consistent with their generation by CK2...
November 9, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29109270/m-current-inhibition-rapidly-induces-a-unique-ck2-dependent-plasticity-of-the-axon-initial-segment
#4
Jonathan Lezmy, Maya Lipinsky, Yana Khrapunsky, Eti Patrich, Lia Shalom, Asher Peretz, Ilya A Fleidervish, Bernard Attali
Alterations in synaptic input, persisting for hours to days, elicit homeostatic plastic changes in the axon initial segment (AIS), which is pivotal for spike generation. Here, in hippocampal pyramidal neurons of both primary cultures and slices, we triggered a unique form of AIS plasticity by selectively targeting M-type K(+) channels, which predominantly localize to the AIS and are essential for tuning neuronal excitability. While acute M-current inhibition via cholinergic activation or direct channel block made neurons more excitable, minutes to hours of sustained M-current depression resulted in a gradual reduction in intrinsic excitability...
November 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29103587/conditioned-media-from-the-renal-cell-carcinoma-cell-line-786-o-drives-human-blood-monocytes-to-a-monocytic-myeloid-derived-suppressor-cell-phenotype
#5
Shannon L Okada, Randi M Simmons, Secil Franke-Welch, Thuy H Nguyen, Alan J Korman, Stacey R Dillon, Debra G Gilbertson
Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells critical in mediating immune suppression in cancer patients. To develop an in vitro assay system that functionally mimics the tumor microenvironment, we cultured human monocytes with conditioned media from several cancer cell lines. Conditioned media from five tumor cell lines induced survival and differentiation of monocytes into cells characteristically similar to macrophages and MDSCs. Notably, media from the 786.O renal cell carcinoma line induced monocytes to acquire a monocytic MDSC phenotype characterized by decreased HLA-DR expression, increased nitric oxide production, enhanced proliferation, and ability to suppress autologous CD3(+) T cell proliferation...
October 31, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29100039/xrcc1-mediated-repair-of-strand-breaks-independent-of-pnkp-binding
#6
Julie K Horton, Donna F Stefanick, Ming-Lang Zhao, Agnes K Janoshazi, Natalie R Gassman, Hannah J Seddon, Samuel H Wilson
Repair of DNA-protein crosslinks and oxidatively damaged DNA base lesions generates intermediates with nicks or gaps with abnormal and blocked 3'-phosphate and 5'-OH ends that prevent the activity of DNA polymerases and ligases. End cleaning in mammalian cells by Tdp1 and PNKP produces the conventional 3'-OH and 5'-phosphate DNA ends suitable for completion of repair. This repair function of PNKP is facilitated by its binding to the scaffold protein XRCC1, and phosphorylation of XRCC1 by CK2 at several consensus sites enables PNKP binding and recruitment to DNA damage...
December 2017: DNA Repair
https://www.readbyqxmd.com/read/29097596/ck2-oppositely-modulates-l-dopa-induced-dyskinesia-via-striatal-projection-neurons-expressing-d1-or-d2-receptors
#7
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
#8
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/29059378/characterization-of-the-aplf-fha-xrcc1-phosphopeptide-interaction-and-its-structural-and-functional-implications
#9
Kyungmin Kim, Lars C Pedersen, Thomas W Kirby, Eugene F DeRose, Robert E London
Aprataxin and PNKP-like factor (APLF) is a DNA repair factor containing a forkhead-associated (FHA) domain that supports binding to the phosphorylated FHA domain binding motifs (FBMs) in XRCC1 and XRCC4. We have characterized the interaction of the APLF FHA domain with phosphorylated XRCC1 peptides using crystallographic, NMR, and fluorescence polarization studies. The FHA-FBM interactions exhibit significant pH dependence in the physiological range as a consequence of the atypically high pK values of the phosphoserine and phosphothreonine residues and the preference for a dianionic charge state of FHA-bound pThr...
October 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29058176/demonstration-of-subcellular-migration-of-ck2%C3%AE-localization-from-nucleus-to-sarco-endo-plasmic-reticulum-in-mammalian-cardiomyocytes-under-hyperglycemia
#10
Ceylan Verda Bitirim, Erkan Tuncay, Belma Turan
The cellular control of glucose uptake and glycogen metabolism in mammalian tissues is in part mediated through the regulation of protein-serine/threonine kinases including CK2. Although it participates to several cellular signaling processes, however, its subcellular localization is not well-defined while some documents mentioned its localization change under pathological conditions. The activation/phosphorylation of some proteins including Zn(2+)-transporter ZIP7 in cardiomyocytes is controlled with CK2α, thereby, inducing changes in the level of intracellular free Zn(2+) ([Zn(2+)] i )...
October 20, 2017: Molecular and Cellular Biochemistry
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
#11
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
#12
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/29021214/casein-kinase-ii-phosphorylation-of-cyclin-f-at-serine-621-regulates-the-lys48-ubiquitylation-e3-ligase-activity-of-the-scf-cyclin-f-complex
#13
Albert Lee, Stephanie L Rayner, Alana De Luca, Serene S L Gwee, Marco Morsch, Vinod Sundaramoorthy, Hamideh Shahheydari, Audrey Ragagnin, Bingyang Shi, Shu Yang, Kelly L Williams, Emily K Don, Adam K Walker, Katharine Y Zhang, Justin J Yerbury, Nicholas J Cole, Julie D Atkin, Ian P Blair, Mark P Molloy, Roger S Chung
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that is characterized by progressive weakness, paralysis and muscle loss often resulting in patient death within 3-5 years of diagnosis. Recently, we identified disease-linked mutations in the CCNF gene, which encodes the cyclin F protein, in cohorts of patients with familial and sporadic ALS and frontotemporal dementia (FTD) (Williams KL et al 2016 Nat. Commun.7, 11253. (doi:10.1038/ncomms11253)). Cyclin F is a part of a Skp1-Cul-F-box (SCF) E3 ubiquitin-protein ligase complex and is responsible for ubiquitylating proteins for degradation by the proteasome...
October 2017: Open Biology
https://www.readbyqxmd.com/read/28994305/plant-homeodomain-finger-protein-2-as-a-novel-ikaros-target-in-acute-lymphoblastic-leukemia
#14
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/28992316/phosphorylation-of-cbx2-controls-its-nucleosome-binding-specificity
#15
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/28969692/role-of-protein-kinases-ck1%C3%AE-and-ck2-in-multiple-myeloma-regulation-of-pivotal-survival-and-stress-managing-pathways
#16
REVIEW
Sabrina Manni, Marilena Carrino, Francesco Piazza
Multiple myeloma (MM) is a malignant tumor of transformed plasma cells. MM pathogenesis is a multistep process. This cancer can occur de novo (rarely) or it can develop from monoclonal gammopathy of undetermined significance (most of the cases). MM can be asymptomatic (smoldering myeloma) or clinically active. Malignant plasma cells exploit intrinsic and extrinsic bone marrow microenvironment-derived growth signals. Upregulation of stress-coping pathways is also instrumental to maintain MM cell growth. The phylogenetically related Ser/Thr kinases CSNK1A1 (CK1α) and CSNK2 (CK2) have recently gained a growing importance in hematologic malignancies arising both from precursors and from mature blood cells...
October 2, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28964816/quinalizarin-inhibits-adipogenesis-through-down-regulation-of-transcription-factors-and-microrna-modulation
#17
Lisa Schwind, Lisa Nalbach, Andreas D Zimmer, Katja B Kostelnik, Jennifer Menegatti, Friedrich Grässer, Claudia Götz, Mathias Montenarh
BACKGROUND: Protein kinase CK2 is induced early in adipogenesis whereas later on, this kinase seems to be dispensable. Here, we have analysed how CK2 might be involved in early steps of differentiation of 3T3-L1 cells. METHODS: 3T3-L1 cells were differentiated to adipocytes in the absence or presence of quinalizarin. The expression and localization of important transcription factors was analysed by Western blot and immunofluorescence. DNA binding capacity and transactivation was analysed with pull-down assays and with luciferase reporter experiments, respectively...
December 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28951560/therapeutic-targeting-of-ck2-in-acute-and-chronic-leukemias
#18
REVIEW
F Buontempo, J A McCubrey, E Orsini, M Ruzzene, A Cappellini, A Lonetti, C Evangelisti, F Chiarini, C Evangelisti, J T Barata, A M Martelli
CK2 is a ubiquitously expressed, constitutively active Ser/Thr protein kinase, which is considered the most pleiotropic protein kinase in the human kinome. Such a pleiotropy explains the involvement of CK2 in many cellular events. However, its predominant roles are stimulation of cell growth and prevention of apoptosis. High levels of CK2 mRNA and protein are associated with CK2 pathological functions in human cancers. Over the last decade, basic and translational studies have provided evidence of CK2 as a pivotal molecule driving the growth of different blood malignancies...
September 27, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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/28928125/ck2%C3%AE-critically-regulates-thrombopoiesis-and-ca-2-triggered-platelet-activation-in-arterial-thrombosis-in-vivo
#20
Patrick Münzer, Britta Walker-Allgaier, Sascha Geue, Friederike Langhauser, Eva Geuss, David Stegner, Katja Aurbach, Daniela Semeniak, Madhumita Chatterjee, Irene Gonzalez Menendez, Melanie Märklin, Leticia Quintanilla-Martinez, Helmut R Salih, David W Litchfield, Thierry Buchou, Christoph Kleinschnitz, Florian Lang, Bernhard Nieswandt, Irina Pleines, Harald Schulze, Meinrad Gawaz, Oliver Borst
Platelets, anucleated megakaryocyte-derived cells, play a major role in hemostasis and arterial thrombosis. While protein kinase Casein Kinase 2 (CK2) is readily detected in megakaryocytes and platelets, the impact of CK2-dependent signaling on megakaryocyte/platelet (patho-) physiology has remained elusive. The present study explored the impact of the CK2 regulatory β-subunit on platelet biogenesis and activation. Megakaryocyte/platelet-specific genetic deletion of CK2β (ck2β(-/-) ) in mice resulted in a significant macrothrombocytopenia and an increased extramedullar megakaryopoiesis with enhanced proportion of premature platelets...
September 19, 2017: Blood
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