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https://www.readbyqxmd.com/read/28106831/ablation-of-protein-kinase-ck2%C3%AE-in-skeletal-muscle-fibers-interferes-with-their-oxidative-capacity
#1
Nane Eiber, Luca Simeone, Said Hashemolhosseini
The tetrameric protein kinase CK2 was identified playing a role at neuromuscular junctions by studying CK2β-deficient muscle fibers in mice, and in cultured immortalized C2C12 muscle cells after individual knockdown of CK2α and CK2β subunits. In muscle cells, CK2 activity appeared to be at least required for regular aggregation of nicotinic acetylcholine receptors, which serves as a hallmark for the presence of a postsynaptic apparatus. Here, we set out to determine whether any other feature accompanies CK2β-deficient muscle fibers...
January 19, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28105499/cx4945-suppresses-the-growth-of-castration-resistant-prostate-cancer-cells-by-reducing-ar-v7-expression
#2
Chuangzhong Deng, Jieping Chen, Shengjie Guo, Yanjun Wang, Qianghua Zhou, Zaishang Li, Xingping Yang, Xingsu Yu, Zhenfeng Zhang, Fangjian Zhou, Hui Han, Kai Yao
PURPOSE: The aberrant expression of casein kinase 2 (CK2) has been reported to be involved in the tumorigenesis and progression of prostate cancer. The inhibition of CK2 activity represses androgen-dependent prostate cancer cells by attenuating the androgen receptor (AR) signaling pathway. In this study, we examined the effect of CK2 inhibition in castration-resistant prostate cancer (CRPC) cells, in which AR variants (ARVs) play a predominant role. METHODS: A newly synthetic CK2 selective inhibitor CX4945 was utilized to study the effect of CK2 inhibition in CRPC cells by CCK8 assay and colony formation assay...
January 19, 2017: World Journal of Urology
https://www.readbyqxmd.com/read/28094268/contribution-of-classical-end-joining-to-pten-inactivation-in-p53-mediated-glioblastoma-formation-and-drug-resistant-survival
#3
Youn-Jung Kang, Barbara Balter, Eva Csizmadia, Brian Haas, Himanshu Sharma, Roderick Bronson, Catherine T Yan
DNA repair gene defects are found in virtually all human glioblastomas, but the genetic evidence for a direct role remains lacking. Here we demonstrate that combined inactivation of the XRCC4 non-homologous end-joining (NHEJ) DNA repair gene and p53 efficiently induces brain tumours with hallmark characteristics of human proneural/classical glioblastoma. The murine tumours exhibit PTEN loss of function instigated by reduced PTEN mRNA, and increased phosphorylated inactivation and stability as a consequence of aberrantly elevated CK2 provoked by p53 ablation and irrevocably deregulated by NHEJ inactivation...
January 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28089218/nkg2d-signaling-the-immune-subversive-side-of-hdac3
#4
Alicia R Folgueras, Segundo Gonzalez, Alejandro López-Soto
Natural killer (NK) cells are alerted to infected and transformed cells by local upregulation of ligands for the NK-activating receptor NKG2D. In a recent report, Greene et al. unveil a new mechanism that induces the expression of the NKG2D ligand retinoic acid early-inducible (RAE-1) in response to murine cytomegalovirus (MCMV) infection through inhibition of casein kinase 2 (CK2), an activator of the repressor histone deacetylase HDAC3.
January 11, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28077325/role-of-14-3-3-sigma-in-over-expression-of-p-gp-by-rifampin-and-paclitaxel-stimulation-through-interaction-with-pxr
#5
So Won Kim, Md Hasanuzzaman, Munju Cho, Nam Hyun Kim, Hye-Young Choi, Jung Woo Han, Hyun June Park, Ji Won Oh, Jae-Gook Shin
In this study, we presented the role of 14-3-3σ to activate CK2-Hsp90β-PXR-MDR1 pathway on rifampin and paclitaxel treated LS174T cells and in vivo LS174T cell-xenografted nude mouse model. Following several in vitro and in vivo experiments, rifampin and paclitaxel were found to be stimulated the CK2-Hsp90β-PXR-MDR1 pathway. Of the proteins in this pathway, Pregnane X receptor (PXR) is a representative transcription factor of multidrug resistance protein 1 (MDR1). We constructed FLAG-PXR-LS174T stable cell lines and discovered 22 proteins that interacted with PXR on rifampin treatment...
January 7, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28075359/development-of-pharmacophore-model-for-indeno-1-2-b-indoles-as-human-protein-kinase-ck2-inhibitors-and-database-mining
#6
Samer Haidar, Zouhair Bouaziz, Christelle Marminon, Tuomo Laitinen, Antti Poso, Marc Le Borgne, Joachim Jose
Protein kinase CK2, initially designated as casein kinase 2, is an ubiquitously expressed serine/threonine kinase. This enzyme, implicated in many cellular processes, is highly expressed and active in many tumor cells. A large number of compounds has been developed as inhibitors comprising different backbones. Beside others, structures with an indeno[1,2-b]indole scaffold turned out to be potent new leads. With the aim of developing new inhibitors of human protein kinase CK2, we report here on the generation of common feature pharmacophore model to further explain the binding requirements for human CK2 inhibitors...
January 9, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28067771/ck2-an-emerging-target-for-neurological-and-psychiatric-disorders
#7
REVIEW
Julia Castello, Andre Ragnauth, Eitan Friedman, Heike Rebholz
Protein kinase CK2 has received a surge of attention in recent years due to the evidence of its overexpression in a variety of solid tumors and multiple myelomas as well as its participation in cell survival pathways. CK2 is also upregulated in the most prevalent and aggressive cancer of brain tissue, glioblastoma multiforme, and in preclinical models, pharmacological inhibition of the kinase has proven successful in reducing tumor size and animal mortality. CK2 is highly expressed in the mammalian brain and has many bona fide substrates that are crucial in neuronal or glial homeostasis and signaling processes across synapses...
January 5, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28067769/identification-of-a-potent-allosteric-inhibitor-of-human-protein-kinase-ck2-by-bacterial-surface-display-library-screening
#8
Christian Nienberg, Claudia Garmann, Andreas Gratz, Andre Bollacke, Claudia Götz, Joachim Jose
Human protein kinase CK2 has emerged as promising target for the treatment of neoplastic diseases. The vast majority of kinase inhibitors known today target the ATP binding site, which is highly conserved among kinases and hence leads to limited selectivity. In order to identify non-ATP competitive inhibitors, a 12-mer peptide library of 6 × 10⁵ variants was displayed on the surface of E. coli by autodisplay. Screening of this peptide library on variants with affinity to CK2 was performed by fluorophore-conjugated CK2 and subsequent flow cytometry...
January 5, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28052864/lipopolysaccharide-inhibits-colonic-biotin-uptake-via-interference-with-membrane-expression-of-its-transporter-a-role-for-casein-kinase-2-mediated-pathway
#9
Ram Lakhan, Hamid M Said
Biotin (vitamin B7), an essential micronutrient for normal cellular functions, is obtained from both dietary sources as well as gut microbiota. Absorption of biotin in both the small and large intestine is via a carrier-mediated process that involves the sodium-dependent multivitamin transporter, SMVT. While different physiological and molecular aspects of intestinal biotin uptake have been delineated, nothing is known about the effect of LPS on the process. We addressed this issue using in vitro (human colonic epithelial NCM460 cells) and in vivo (mice) models of LPS exposure...
January 4, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28045438/d11-mediated-inhibition-of-protein-kinase-ck2-impairs-hif-1%C3%AE-mediated-signaling-in-human-glioblastoma-cells
#10
Susanne Schaefer, Tina H Svenstrup, Mette Fischer, Barbara Guerra
Compelling evidence indicates that protein kinase CK2 plays an important role in many steps of cancer initiation and progression, therefore, the development of effective and cell-permeable inhibitors targeting this kinase has become an important objective for the treatment of a variety of cancer types including glioblastoma. We have recently identified 1,3-dichloro-6-[(E)-((4-methoxyphenyl)imino)methyl]dibenzo(b,d)furan-2,7-diol (D11) as a potent and selective inhibitor of protein kinase CK2. In this study, we have further characterized this compound and demonstrated that it suppresses CK2 kinase activity by mixed type inhibition (KI 7...
January 1, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28043654/selected-flavonoid-compounds-as-promising-inhibitors-of-protein-kinase-ck2%C3%AE-and-ck2%C3%AE-the-catalytic-subunits-of-ck2
#11
Andrea Baier, Anna Galicka, Jolanta Nazaruk, Ryszard Szyszka
CK2 is a ubiquitous protein kinase involved in many cell functions. During the last years it became an interesting target in cancer research. A series of flavonoid compounds was tested as inhibitors of protein kinase CK2. Several substances were found to be highly active against both catalytic subunits with IC50 values below 1 μM in case of CK2α'. The most promising inhibitor we identified is chrysoeriol with IC50 values of 250 and 34 nM for CK2α and CK2α', respectively.
December 30, 2016: Phytochemistry
https://www.readbyqxmd.com/read/28036067/drosophila-protein-kinase-ck2-genetics-regulatory-complexity-and-emerging-roles-during-development
#12
REVIEW
Mohna Bandyopadhyay, Scott Arbet, Clifton P Bishop, Ashok P Bidwai
CK2 is a Ser/Thr protein kinase that is highly conserved amongst all eukaryotes. It is a well-known oncogenic kinase that regulates vital cell autonomous functions and animal development. Genetic studies in the fruit fly Drosophila are providing unique insights into the roles of CK2 in cell signaling, embryogenesis, organogenesis, neurogenesis, and the circadian clock, and are revealing hitherto unknown complexities in CK2 functions and regulation. Here, we review Drosophila CK2 with respect to its structure, subunit diversity, potential mechanisms of regulation, developmental abnormalities linked to mutations in the gene encoding CK2 subunits, and emerging roles in multiple aspects of eye development...
December 29, 2016: Pharmaceuticals
https://www.readbyqxmd.com/read/28036027/the-phosphorylation-of-pdx-1-by-protein-kinase-ck2-is-crucial-for-its-stability
#13
Sabrina Klein, Rui Meng, Mathias Montenarh, Claudia Götz
The homeodomain protein PDX-1 is a critical regulator of pancreatic development and insulin production in pancreatic β-cells. We have recently shown that PDX-1 is a substrate of protein kinase CK2; a multifunctional protein kinase which is implicated in the regulation of various cellular aspects, such as differentiation, proliferation, and survival. The CK2 phosphorylation site of PDX-1 is located within the binding region of the E3 ubiquitin ligase adaptor protein PCIF1. To study the interaction between PDX-1 and PCIF1 we used immunofluorescence analysis, co-immunoprecipitation, GST-pull-down studies, and proximity ligation assay (PLA)...
December 28, 2016: Pharmaceuticals
https://www.readbyqxmd.com/read/28031292/protein-kinase-ck2-modulates-hsj1-function-through-phosphorylation-of-the-uim2-domain
#14
Daniele Ottaviani, Oriano Marin, Giorgio Arrigoni, Cinzia Franchin, Jordi Vilardell, Michele Sandre, Wenwen Li, David A Parfitt, Lorenzo A Pinna, Michael E Cheetham, Maria Ruzzene
HSJ1 (DNAJB2), a member of the DNAJ family of molecular chaperones, is a key player in neuronal proteostasis maintenance. It binds ubiquitylated proteins through its Ubiquitin Interacting Motifs (UIMs) and facilitates their delivery to the proteasome for degradation. Mutations in the DNAJB2 gene lead to inherited neuropathies such as Charcot-Marie-Tooth type-2, distal hereditary motor neuropathies, spinal muscular atrophy with parkinsonism and the later stages can resemble amyotrophic lateral sclerosis. HSJ1 overexpression can reduce aggregation of neurodegeneration-associated proteins in vitro and in vivo; however, the regulation of HSJ1 function is little understood...
December 28, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28030830/ikaros-regulation-of-the-bcl6-bach2-axis-and-its-clinical-relevance-in-acute-lymphoblastic-leukemia
#15
Zheng Ge, Xilian Zhou, Yan Gu, Qi Han, Jianyong Li, Baoan Chen, Qinyu Ge, Elanora Dovat, Jonathon L Payne, Tianyu Sun, Chunhua Song, Sinisa Dovat
B-Cell CLL/Lymphoma 6 (BCL6) is a proto-oncogene that is highly expressed in acute lymphoblastic leukemia (ALL). BTB and CNC Homology 1 Basic Leucine Zipper Transcription Factor 2 (BACH2) is a suppressor of transcription. The BACH2-BCL6 balance controls selection at the pre-B cell receptor checkpoint by regulating p53 expression. However, the underlying mechanism and the clinical relevance of the BCL6/BACH2 axis are unknown. Here, we found that Ikaros, a tumor suppressor encoded by IKZF1, directly binds to both the BCL6 and BACH2 promoters where it suppresses BCL6 and promotes BACH2 expression in B-cell ALL (B-ALL) cells...
December 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/28030587/cd5-ck2-signaling-modulates-erk-activation-and-thymocyte-survival
#16
Carlos A Mier-Aguilar, Kevin S Cashman, Chander Raman, Gloria Soldevila
CD5 is well recognized for its importance in thymic selection. Although this property of CD5 has been attributed to its ITIM-domain dependent regulation of TCR-signal strength, the mechanism has not been established. A second major signaling domain within the cytoplasmic tail of CD5 is a CK2 binding/activation domain (CD5-CK2BD). Using a gene-targeted mouse in which the CD5-CK2BD is selectively ablated (CD5-ΔCK2BD), we determined that loss of function of CD5-CK2 signaling in a MHC-II selecting TCR transgenic (OT-II) mouse resulted in decrease in double positive (DP) thymocytes, which correlated with enhanced apoptosis...
2016: PloS One
https://www.readbyqxmd.com/read/28027904/esculentoside-a-suppresses-lipopolysaccharide-induced-pro-inflammatory-molecule-production-partially-by-casein-kinase-2
#17
Yinghua Li, Yan Cao, Jing Xu, Lei Qiu, Weiheng Xu, Jie Li, Yunlong Song, Bin Lu, Zhenlin Hu, Junping Zhang
ETHNOPHARMACOLOGICAL RELEVANCE: Esculentoside A (EsA) is a saponin isolated from the root of Phytolacca esculenta, an herb which has long been used in Traditional Chinese Medicine for various inflammatory diseases. EsA has been reported to have potent anti-inflammatory properties both in vitro and in vivo. AIM OF THE STUDY: The present study focused on the molecular mechanism of EsA for its anti-inflammatory effects in RAW264.7 cells stimulated with lipopolysaccharide (LPS)...
December 24, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28011258/identification-of-kinases-phosphorylating-13-sites-in-the-nuclear-dna-binding-protein-nucks
#18
Kirsten Grundt, Bernd Thiede, Anne Carine Østvold
NUCKS is a vertebrate specific, nuclear and DNA-binding phospho protein. The protein is highly expressed in rapidly dividing cells, and is overexpressed in a number of cancer tissues. The phosphorylation of NUCKS is cell cycle and DNA-damage regulated, but little is known about the responsible kinases. By utilizing in vitro and in vivo phosphorylation assays using isolated NUCKS as well as synthetic NUCKS-derived peptides in combination with mass spectrometry, phosphopeptide mapping, phosphphoamino acid analyses, phosphospecific antibodies and the use of specific kinase inhibitors, we found that NUCKS is phosphorylated on 11 sites by CK2...
December 21, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28009816/the-new-role-for-an-old-kinase-protein-kinase-ck2-regulates-metal-ion-transport
#19
REVIEW
Adam J Johnson, Ming J Wu
The pleiotropic serine/threonine protein kinase CK2 was the first kinase discovered. It is renowned for its role in cell proliferation and anti-apoptosis. The complexity of this kinase is well reflected by the findings of past decades in terms of its heterotetrameric structure, subcellular location, constitutive activity and the extensive catalogue of substrates. With the advent of non-biased high-throughput functional genomics such as genome-wide deletion mutant screening, novel aspects of CK2 functionality have been revealed...
December 21, 2016: Pharmaceuticals
https://www.readbyqxmd.com/read/27998980/glutamate-counteracts-dopamine-pka-signaling-via-dephosphorylation-of-darpp-32-ser97-and-alteration-of-its-cytonuclear-distribution
#20
Akinori Nishi, Miriam Matamales, Veronica Musante, Emmanuel Valjent, Mahomi Kuroiwa, Yosuke Kitahara, Heike Rebholz, Paul Greengard, Jean-Antoine Girault, Angus C Nairn
The interaction of glutamate and dopamine in the striatum is heavily dependent on signaling pathways that converge on the regulatory protein DARPP-32. The efficacy of dopamine/D1 receptor/PKA signaling is regulated by DARPP-32 phosphorylated at Thr34 (the PKA-site), a process that inhibits protein phosphatase 1 (PP1), and potentiates PKA action. Activation of dopamine/D1 receptor/PKA signaling also leads to dephosphorylation of DARPP-32 at Ser97 (the CK2-site), leading to localization of phospho-Thr34 DARPP-32 in the nucleus where it also inhibits PP1...
December 20, 2016: Journal of Biological Chemistry
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