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https://www.readbyqxmd.com/read/27909846/benzimidazole-inhibitors-of-protein-kinase-ck2-potently-inhibit-the-activity-of-atypical-protein-kinase-rio1
#1
Konrad Kubiński, Maciej Masłyk, Andrzej Orzeszko
Benzimidazole derivatives of 5,6-dichlorobenzimidazole 1-β-D-ribofuranoside (DRB) comprise the important class of protein kinase CK2 inhibitors. Depending on the structure, benzimidazoles inhibit CK2 with different selectivity and potency. Besides CK2, the compounds can inhibit, with similar activity, other classical eukaryotic protein kinases (e.g. PIM, DYRK, and PKD). The present results show that a majority of the most common CK2 inhibitors can affect the atypical kinase Rio1 in a nanomolar range. Kinetic data confirmed the mode of action of benzimidazoles as typical ATP-competitive inhibitors...
December 1, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27906674/nuclear-localization-of-the-ck2%C3%AE-subunit-correlates-with-poor-prognosis-in-clear-cell-renal-cell-carcinoma
#2
Maj Rabjerg, Barbara Guerra, Aida Oliván-Viguera, Minne Line Nedergaard Mikkelsen, Ralf Köhler, Olaf-Georg Issinger, Niels Marcussen
Protein kinase CK2α, one of the two catalytic isoforms of the protein kinase CK2 has been shown to contribute to tumor development, tumor proliferation and suppression of apoptosis in various malignancies. We conducted this study to investigate CK2 expression in different subtypes of Renal Cell Carcinoma (RCC) and in the benign oncocytoma. qRT-PCR, immunohistochemistry and Western blot analyses revealed that CK2α expression was significantly increased at the mRNA and protein levels in clear cell RCC (ccRCC)...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899804/casein-kinase-2-controls-the-survival-of-normal-thymic-and-leukemic-%C3%AE-%C3%AE-t-cells-via-promotion-of-akt-signaling
#3
S T Ribeiro, M Tesio, J C Ribot, E Macintyre, J T Barata, B Silva-Santos
The thymus is the major site for normal and leukemic T-cell development. The dissection of the molecular determinants of T-cell survival and differentiation is paramount for the manipulation of healthy or transformed T cells in cancer (immuno)therapy. Casein Kinase 2 (CK2) is a serine-threonine protein kinase whose anti-apoptotic functions have been described in various hematological and solid tumors. Here we disclose an unanticipated role of CK2 in healthy human thymocytes that is selective to the γδ T-cell lineage...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27888634/targeting-protein-kinase-ck2-suppresses-bladder-cancer-cell-survival-via-the-glucose-metabolic-pathway
#4
Xiaolei Zhang, Xiao Yang, Chengdi Yang, Peng Li, Wenbo Yuan, Xiaheng Deng, Yidong Cheng, Pengchao Li, Haiwei Yang, Jun Tao, Qiang Lu
Casein kinase 2 (CK2) is a constitutively active serine/threonine kinase that promotes cell proliferation and resists apoptosis. Elevated CK2 expression has been demonstrated in several solid tumors. The expression of CK2α in bladder cancer was elevated in tumor tissues compared with that in adjacent normal tissues. Amplified expression of CK2α was highly correlated with histological grade in bladder cancer(P = 0.024). Knockdown of CK2α in bladder cancer cell lines resulted in a reduction in tumor aerobic glycolysis, accompanied with lower phosphorylated AKT...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27885421/role-of-vernalization-mediated-demethylation-in-the-floral-transition-of-brassica-rapa
#5
Weike Duan, Huijun Zhang, Bei Zhang, Xiaoting Wu, Shuaixu Shao, Ying Li, Xilin Hou, Tongkun Liu
Vernalization-mediated demethylation of BrCKA2 (casein kinase II α-subunit) and BrCKB4 (casein kinase II β-subunit) shorten the period of the clock gene BrCCA1 (circadian clock associated 1) in Brassica rapa. Photoperiod and vernalization are two environmental cues involved in the regulation of floral transition, but the ways in which they interact remain unclear. DNA methylation is one of the main mechanisms involved in controlling the functional state of chromatin and gene expression in response to environmental signals...
November 24, 2016: Planta
https://www.readbyqxmd.com/read/27885263/targeting-high-dynamin-2-dnm2-expression-by-restoring-ikaros-function-in-acute-lymphoblastic-leukemia
#6
Zheng Ge, Yan Gu, Qi Han, Gang Zhao, Min Li, Jianyong Li, Baoan Chen, Tianyu Sun, Sinisa Dovat, Robert Peter Gale, Chunhua Song
Dynamin-2 (DNM2) is a GTPase essential for intracellular vesicle formation and trafficking, cytokinesis and receptor endocytosis. Mutations in DNM2 are common in early T-cell precursor acute lymphoblastic leukemia. However, DNM2 expression in other types of ALL are not reported. We studied DNM2 mRNA level in adults with B- and T-cell ALL. We found DNM2 is more highly expressed compared with normals in both forms of ALL. High DNM2 expression is associated with some clinical and laboratory features, inferior outcomes and with leukaemia cell proliferation...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27881437/casein-kinase-ii-is-required-for-proper-cell-division-and-acts-as-a-negative-regulator-of-centrosome-duplication-in-c-elegans-embryos
#7
Jeffrey C Medley, Megan M Kabara, Michael D Stubenvoll, Lauren E DeMeyer, Mi Hye Song
Centrosomes are the primary microtubule-organizing centers that orchestrate microtubule dynamics during the cell cycle. The correct number of centrosomes is pivotal for establishing bipolar mitotic spindles that ensure accurate segregation of chromosomes. Thus, centrioles must duplicate once per cell cycle, one daughter per mother centriole, the process of which requires highly coordinated actions among core factors and modulators. Protein phosphorylation is shown to regulate the stability, localization and activity of centrosome proteins...
November 23, 2016: Biology Open
https://www.readbyqxmd.com/read/27852853/coat-protein-regulation-by-ck2-cpip-hsp70-and-chip-is-required-for-potato-virus-a-replication-and-coat-protein-accumulation
#8
Andres Lõhmus, Anders Hafrén, Kristiina Mäkinen
: We demonstrate here that coat protein (CP) phosphorylation by protein kinase CK2 and a chaperone system formed by two heat-shock proteins, CP-interacting protein (CPIP) and HSP70, are both essential for Potato virus A (PVA; genus Potyvirus) replication and that all of these host proteins have the capacity to contribute to the level of PVA CP accumulation. An E3 ubiquitin ligase called carboxyl terminus Hsc70-interacting protein (CHIP), which may participate in the CPIP-HSP70-mediated CP degradation, is also needed for robust PVA gene expression...
November 16, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27851782/alpha-b-crystallin-protects-rat-articular-chondrocytes-against-casein-kinase-ii-inhibition-induced-apoptosis
#9
Sung Won Lee, Jee Hyun Rho, Sang Yeob Lee, Seung Hee Yoo, Hye Young Kim, Won Tae Chung, Young Hyun Yoo
Although alpha (α)B-crystallin is expressed in articular chondrocytes, little is known about its role in these cells. Protein kinase casein kinase 2 (CK2) inhibition induces articular chondrocyte death. The present study examines whether αB-crystallin exerts anti-apoptotic activity in articular chondrocytes. Primary rat articular chondrocytes were isolated from knee joint slices. Cells were treated with CK2 inhibitors with or without αB-crystallin siRNA. To examine whether the silencing of αB-crystallin sensitizes rat articular chondrocytes to CK2 inhibition-induced apoptosis, we assessed apoptosis by performing viability assays, mitochondrial membrane potential measurements, flow cytometry, nuclear morphology observations, and western blot analysis...
2016: PloS One
https://www.readbyqxmd.com/read/27825958/simultaneous-blockade-of-interacting-ck2-and-egfr-pathways-by-tumor-targeting-nanobioconjugates-increases-therapeutic-efficacy-against-glioblastoma-multiforme
#10
Szu-Ting Chou, Rameshwar Patil, Anna Galstyan, Pallavi R Gangalum, Webster K Cavenee, Frank B Furnari, Vladimir A Ljubimov, Alexandra Chesnokova, Andrei A Kramerov, Hui Ding, Vida Falahatian, Leila Mashouf, Irving Fox, Keith L Black, Eggehard Holler, Alexander V Ljubimov, Julia Y Ljubimova
Glioblastoma multiforme (GBM) remains the deadliest brain tumor in adults. GBM tumors are also notorious for drug and radiation resistance. To inhibit GBMs more effectively, polymalic acid-based blood-brain barrier crossing nanobioconjugates were synthesized that are delivered to the cytoplasm of cancer cells and specifically inhibit the master regulator serine/threonine protein kinase CK2 and the wild-type/mutated epidermal growth factor receptor (EGFR/EGFRvIII), which are overexpressed in gliomas according to The Cancer Genome Atlas (TCGA) GBM database...
November 5, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27814385/from-proteomic-analysis-to-potential-therapeutic-targets-functional-profile-of-two-lung-cancer-cell-lines-a549-and-sw900-widely-studied-in-pre-clinical-research
#11
Luís Korrodi-Gregório, Vanessa Soto-Cerrato, Rui Vitorino, Margarida Fardilha, Ricardo Pérez-Tomás
Lung cancer is a serious health problem and the leading cause of cancer death worldwide. The standard use of cell lines as in vitro pre-clinical models to study the molecular mechanisms that drive tumorigenesis and access drug sensitivity/effectiveness is of undisputable importance. Label-free mass spectrometry and bioinformatics were employed to study the proteomic profiles of two representative lung cancer cell lines and to unravel the specific biological processes. Adenocarcinoma A549 cells were enriched in proteins related to cellular respiration, ubiquitination, apoptosis and response to drug/hypoxia/oxidative stress...
2016: PloS One
https://www.readbyqxmd.com/read/27808495/quantifying-kinase-specific-phosphorylation-stoichiometry-using-stable-isotope-labeling-in-a-reverse-in-gel-kinase-assay
#12
Xiang Li, Jonathan T Cox, Weiliang Huang, Maureen A Kane, Keqi Tang, Charles J Bieberich
Despite recent advancements in large-scale phospho-proteomics, methods to quantify kinase-specific phosphorylation stoichiometry of protein substrates are lacking. We developed a method to quantify kinase-specific phosphorylation stoichiometry by combining the reverse in-gel kinase assay (RIKA) with high resolution LC-MS. Beginning with predetermined ratios of phosphorylated to non-phosphorylated Protein Kinase CK2 (CK2) substrate molecules, we employed 18O-ATP as the phosphate donor in a RIKA, then quantified the ratio of 18O- versus 16O-labeled tryptic phosphopeptide using high mass accuracy MS...
November 3, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/27807358/autoimmune-disease-ck2-blockade-ameliorates-eae
#13
Sarah Crunkhorn
No abstract text is available yet for this article.
November 3, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27793693/a-ck2-targeted-pt-iv-prodrug-to-disrupt-dna-damage-response
#14
Feihong Chen, Xiaochao Huang, Mian Wu, Shaohua Gou, Weiwei Hu
A Pt(IV) prodrug, Cx-platin, containing CX-4945(a CK2 inhibitor) as an axial ligand was designed and prepared by targeting CK2 to disrupt DNA damage response. In vitro study indicated that Cx-platin had superior cytotoxicity to cisplatin against a number of cancer cell lines with distinct CK2-expressed levels, caused CK2-overexpressed cancer cells death via suppressing CK2-mediated DNA damage repair and reversed cisplatin resistance. Mechanistic investigation suggested that the potent antitumor activity of Cx-platin resulted from its major suppression of CK2-phosphorylated MDC1 to combine FHA domain of aprataxin to DNA double strand breaks (DSBs) caused by improved cellular uptakes of Pt and ATM deactivation...
October 25, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27782092/annexin-1-mediates-microglial-activation-and-migration-via-the-ck2-pathway-during-oxygen-glucose-deprivation-reperfusion
#15
Shuangxi Liu, Yan Gao, Xiaoli Yu, Baoming Zhao, Lu Liu, Yin Zhao, Zhenzhao Luo, Jing Shi
Annexin-1 (ANXA1) has shown neuroprotective effects and microglia play significant roles during central nervous system injury, yet the underlying mechanisms remain unclear. This study sought to determine whether ANXA1 regulates microglial response to oxygen-glucose deprivation/reperfusion (OGD/R) treatment and to clarify the downstream molecular mechanism. In rat hippocampal slices, OGD/R treatment enhanced the ANXA1 expression in neuron, the formyl peptide receptor (FPRs) expression in microglia, and the microglial activation in the CA1 region (cornu ammonis 1)...
October 22, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27769352/phospho-brd4-transcription-plasticity-and-drug-targeting
#16
REVIEW
Cheng-Ming Chiang
BRD4 is an epigenetic regulator and transcription cofactor whose phosphorylation by CK2 and dephosphorylation by PP2A modulates its function in chromatin targeting, factor recruitment, and cancer progression. While the bromodomains of BET family proteins, including BRD4, BRD2, BRD3 and BRDT, have been the primary targets of small compounds such as JQ1, I-BET and MS417 that show promising anticancer effects against some hematopoietic cancer and solid tumors, drug resistance upon prolonged treatment necessitates a better understanding of alternative pathways underlying not only the resistance but also persistent BET protein dependence for identifying new targets and effective combination therapy strategies...
March 2016: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/27758824/ck2-inhibitor-cx-4945-destabilizes-notch1-and-synergizes-with-jq1-against-human-t-acute-lymphoblastic-leukemic-cells
#17
Haiwei Lian, Dun Li, Yun Zhou, Esther Landesman-Bollag, Guanglan Zhang, Nicole M Anderson, Kevin Charles Tang, Justine E Roderick, Michelle A Kelliher, David C Seldin, Hui Fu, Hui Feng
No abstract text is available yet for this article.
October 6, 2016: Haematologica
https://www.readbyqxmd.com/read/27750098/a-role-for-ck2-%C3%AE-subunit-4-in-the-regulation-of-plant-growth-cadmium-accumulation-and-h2o2-content-under-cadmium-stress-in-arabidopsis-thaliana
#18
Jiang Zhu, Wen-Shu Wang, Dan Ma, Lin-Yu Zhang, Feng Ren, Ting-Ting Yuan
Protein kinase CK2, which consists of two α and two β subunits, plays an essential role in plant development and is implicated in plant responses to abiotic stresses, including salt and heat. However, the function of CK2 in response to heavy metals such as cadmium (Cd) has not yet been established. In this study, the transgenic line CKB4ox, which overexpresses CKB4 encoding the CK2β subunit and has elevated CK2 activity, was used to investigate the potential role of CK2 in response to Cd stress in Arabidopsis thaliana...
October 8, 2016: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/27719640/casein-kinase-ii-ck2-as-a-therapeutic-target-for-hematological-malignancies
#19
Chandrika Gowda, Mansi Sachdev, Sunil Muthisami, Malika Kapadia, Lidija Petrovic-Dovat, Melanie Hartman, Yali Ding, Chunhua Song, Jonathon L Payne, Bi-Hua Tan, Sinisa Dovat
BACKGROUND: Casein kinase II (CK2) is a pro-oncogenic protein, which is emerging as a promising therapeutic target in cancer. Recent studies have revealed an important role for CK2 in tumorigenesis. High levels of CK2 are noted in many malignancies including leukemia. Use of CK2 inhibitors in various malignancies including breast, prostate, and lung cancer are being tested. Although many CK2 inhibitors exist, only a few have emerged as selective inhibitors that are potent and effective...
October 6, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27714630/low-intensity-ultrasound-decreases-%C3%AE-synuclein-aggregation-via-attenuation-of-mitochondrial-reactive-oxygen-species-in-mpp-treated-pc12-cells
#20
Mrigendra Bir Karmacharya, Binika Hada, So Ra Park, Byung Hyune Choi
Many studies have shown that mitochondrial dysfunction and the subsequent oxidative stress caused by excessive reactive oxygen species (ROS) generation play a central role in the pathogenesis of Parkinson's disease (PD). We have previously shown that low-intensity ultrasound (LIUS) could reduce ROS generation by L-buthionine-(S,R)-sulfoximine (BSO) in retinal pigment epithelial cells. In this study, we studied the effects of LIUS stimulation on the ROS-dependent α-synuclein aggregation in 1-methyl-4-phenylpyridinium ion (MPP(+))-treated PC12 cells...
October 6, 2016: Molecular Neurobiology
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