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https://www.readbyqxmd.com/read/28916659/hybrid-of-dna-targeting-chlorambucil-with-pt-iv-species-to-reverse-drug-resistances
#1
Feihong Chen, Gang Xu, Xiaodong Qin, Xiufeng Jin, Shaohua Gou
Two hybrids were designed and prepared by addition of a chlorambucil unit to an axial position of the Pt(IV) complex derived from DN603 or DN604 which was recently found to exhibit significant anticancer activity and low toxicity. Cytotoxicity of two compounds against two pairs of cisplatin sensitive and resistant cancer cell lines indicated that compound 5 had superior antitumor activity to cisplatin and chlorambucil via suppressing DNA damage repair to reverse drugs resistances. Mechanistic investigation suggested that the potent antitumor activity of 5 arose from its major suppression of CK2-mediated MRE11-RAD50-NBS1(MRN) complex promotion of DNA double-strand breaks (DSBs) repair...
September 15, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28883547/casein-kinase-2-is-a-critical-determinant-of-the-balance-of-th17-and-treg-cell-differentiation
#2
Sung Woong Jang, Soo Seok Hwang, Hyeong Su Kim, Keoung Oh Lee, Min Kyung Kim, Wonyong Lee, Kiwan Kim, Gap Ryol Lee
Th17 cells promote inflammatory reactions, whereas regulatory T (Treg) cells inhibit them. Thus, the Th17/Treg cell balance is critically important in inflammatory diseases. However, the molecular mechanisms underlying this balance are unclear. Here, we demonstrate that casein kinase 2 (CK2) is a critical determinant of the Th17/Treg cell balance. Both the inhibition of CK2 with a specific pharmacological inhibitor, CX-4945, and its small hairpin RNA (shRNA)-mediated knockdown suppressed Th17 cell differentiation but reciprocally induced Treg cell differentiation in vitro...
September 8, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28879772/brain-membrane-proteome-and-phosphoproteome-reveal-molecular-basis-associating-with-nursing-and-foraging-behaviors-of-honeybee-workers
#3
Bin Han, Yu Fang, Mao Feng, Han Hu, Yue Hao, Chuan Ma, Xinmei Huo, Lifeng Meng, Xufeng Zhang, Fan Wu, Jianke Li
The brain is a vital organ in regulating complex social behaviors of honeybees including learning and memory. Knowledge of how brain membrane proteins and their phosphorylation underlie the age-related behavioral polyethism is still lacking. A hitherto age-resolved brain membrane proteome and phosphoproteome were reported in adult worker bees from two strains of honeybee (Apis mellifera ligustica): Italian bee (ITB) and Royal Jelly bee (RJB), a line selected from ITB for increased RJ outputs over 4 decades...
September 7, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28878488/research-progress-on-the-autonomous-flowering-time-pathway-in-arabidopsis
#4
REVIEW
Jing-Zhi Cheng, Yu-Ping Zhou, Tian-Xiao Lv, Chu-Ping Xie, Chang-En Tian
The transition from vegetative to reproductive growth phase is a pivotal and complicated process in the life cycle of flowering plants which requires a comprehensive response to multiple environmental aspects and endogenous signals. In Arabidopsis, six regulatory flowering time pathways have been defined by their response to distinct cues, namely photoperiod, vernalization, gibberellin, temperature, autonomous and age pathways, respectively. Among these pathways, the autonomous flowering pathway accelerates flowering independently of day length by inhibiting the central flowering repressor FLC...
July 2017: Physiology and Molecular Biology of Plants: An International Journal of Functional Plant Biology
https://www.readbyqxmd.com/read/28873435/tgf-%C3%AE-signaling-is-an-effective-target-to-impair-survival-and-induce-apoptosis-of-human-cholangiocarcinoma-cells-a-study-on-human-primary-cell-cultures
#5
Anna Maria Lustri, Sabina Di Matteo, Alice Fraveto, Daniele Costantini, Alfredo Cantafora, Chiara Napoletano, Maria Consiglia Bragazzi, Felice Giuliante, Agostino M De Rose, Pasquale B Berloco, Gian Luca Grazi, Guido Carpino, Domenico Alvaro
Cholangiocarcinoma (CCA) and its subtypes (mucin- and mixed-CCA) arise from the neoplastic transformation of cholangiocytes, the epithelial cells lining the biliary tree. CCA has a high mortality rate owing to its aggressiveness, late diagnosis and high resistance to radiotherapy and chemotherapeutics. We have demonstrated that CCA is enriched for cancer stem cells which express epithelial to mesenchymal transition (EMT) traits, with these features being associated with aggressiveness and drug resistance. TGF-β signaling is upregulated in CCA and involved in EMT...
2017: PloS One
https://www.readbyqxmd.com/read/28858215/stem-cell-like-properties-of-ck2%C3%AE-down-regulated-mammary-cells
#6
Eve Duchemin-Pelletier, Megghane Baulard, Elodie Spreux, Magali Prioux, Mithila Burute, Baharia Mograbi, Laurent Guyon, Manuel Théry, Claude Cochet, Odile Filhol
The ubiquitous protein kinase CK2 has been demonstrated to be overexpressed in a number of human tumours. This enzyme is composed of two catalytic α or α' subunits and a dimer of β regulatory subunits whose expression levels are probably implicated in CK2 regulation. Several recent papers reported that unbalanced expression of CK2 subunits is sufficient to drive epithelial to mesenchymal transition, a process involved in cancer invasion and metastasis. Herein, through transcriptomic and miRNA analysis together with comparison of cellular properties between wild type and CK2β-knock-down MCF10A cells, we show that down-regulation of CK2β subunit in mammary epithelial cells induces the acquisition of stem cell-like properties associated with perturbed polarity, CD44(high)/CD24(low) antigenic phenotype and the ability to grow under anchorage-independent conditions...
August 31, 2017: Cancers
https://www.readbyqxmd.com/read/28837260/selective-biligand-inhibitor-of-ck2-increases-caspase-3-activity-in-cancerous-cells-and-inhibits-platelet-aggregation
#7
Hedi Rahnel, Kaido Viht, Darja Lavogina, Olga Mazina, Tõiv Haljasorg, Erki Enkvist, Asko Uri
The pleiotropic nature, role in many cellular processes, and constitutive activity of protein kinase CK2 exemplify its importance in a number of diseases, e.g. thrombosis and cancer. Compounds developed in this paper represent a novel class of biologically active scaffold that may be developed into promising drug candidates, but also applied to study the yet still unspecified pathways regulated by CK2. Biligand inhibitors of CK2 were constructed by conjugating 4-(2-amino-1,3-thiazol-5-yl)benzoic acid and carboxylate-rich peptoids...
August 24, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28803999/growth-arrest-and-morphological-changes-triggered-by-emodin-on-trypanosoma-cruzi-epimastigotes-cultivated-in-axenic-medium
#8
Ana R De Lima, Karem Noris-Suárez, Antonio Bretaña, Victor T Contreras, Maria C Navarro, Luis Pérez-Ybarra, José Bubis
Emodin is an anthraquinone obtained from Rheum palmatum rootstocks. Here we tested the cytotoxic effects of emodin on Trypanosoma cruzi epimastigotes, as well as the morphological changes that were induced by this compound in the parasite. Emodin was permeable and blocked in vitro cell division of T. cruzi epimastigotes in axenic medium, causing growth arrest in a dose-dependent but reversible manner. Emodin-exposed epimastigotes underwent duplication of organelles, such as the nucleus, kinetoplast and flagellum, but were incapable of completing cytokinesis...
August 10, 2017: Biochimie
https://www.readbyqxmd.com/read/28798693/phosphorylation-modulates-ameloblastin-self-assembly-and-ca-2-binding
#9
Øystein Stakkestad, Ståle P Lyngstadaas, Bernd Thiede, Jiri Vondrasek, Bjørn S Skålhegg, Janne E Reseland
Ameloblastin (AMBN), an important component of the self-assembled enamel extra cellular matrix, contains several in silico predicted phosphorylation sites. However, to what extent these sites actually are phosphorylated and the possible effects of such post-translational modifications are still largely unknown. Here we report on in vitro experiments aimed at investigating what sites in AMBN are phosphorylated by casein kinase 2 (CK2) and protein kinase A (PKA) and the impact such phosphorylation has on self-assembly and calcium binding...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28748912/a-novel-allosteric-site-in-casein-kinase-2%C3%AE-discovered-using-combining-bioinformatics-and-biochemistry-methods
#10
Hai-Ming Jiang, Jiang-Kai Dong, Kun Song, Tong-Dan Wang, Wen-Kang Huang, Jing-Miao Zhang, Xiu-Yan Yang, Ying Shen, Jian Zhang
Casein kinase 2 (CK2) is a highly pleiotropic serine-threonine kinase, which catalyzed phosphorylation of more than 300 proteins that are implicated in regulation of many cellular functions, such as signal transduction, transcriptional control, apoptosis and the cell cycle. On the other hand, CK2 is abnormally elevated in a variety of tumors, and is considered as a promising therapeutic target. The currently available ATP-competitive CK2 inhibitors, however, lack selectivity, which has impeded their development in cancer therapy...
July 27, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28744813/inhibition-of-protein-kinase-ck2-sensitizes-non-small-cell-lung-cancer-cells-to-cisplatin-via-upregulation-of-pml
#11
Bo Yang, Jinhong Yao, Bai Li, Guoguang Shao, Yongsheng Cui
Non-small cell lung carcinoma (NSCLC), a malignancy of lungs, is very aggressive and usually ends up with a dismal prognosis. Cisplatin (CDDP)-based systemic chemotherapy is the main pharmaceutical approach for treating NSCLC, but its effect is discounted by some hitherto unknown reasons. Thus, this study is dedicated to improving the efficacy of CDDP. Our results show that combining use of CDDP with CK2 siRNA or inhibitor is more efficient in suppressing cancer cell growth and promoting apoptosis than use of CDDP alone...
July 25, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28743511/raf-1-ck2-and-rhoa-rock-signaling-promote-tnf-%C3%AE-mediated-endothelial-apoptosis-via-regulating-vimentin-cytoskeleton
#12
Lifeng Yang, Lian Tang, Fan Dai, Guoliang Meng, Runting Yin, Xiaole Xu, Wenjuan Yao
Both RhoA/ROCK and Raf-1/CK2 pathway play essential roles in cell proliferation, apoptosis, differentiation, and multiple other common cellular functions. We previously reported that vimentin is responsible for TNF-α-induced cell apoptosis. Herein, we investigated the regulation of RhoA/ROCK and Raf-1/CK2 signaling on vimentin filaments and endothelial apoptosis mediated by TNF-α. Treatment with TNF-α significantly induced the activation of RhoA and ROCK, and the expression of ROCK1. RhoA deficiency could obviously inhibit ROCK activation and ROCK1 expression induced by TNF-α...
August 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28738012/evaluation-of-protein-kinase-ck2-as-a-therapeutic-target-for-squamous-cell-carcinoma-of-cats
#13
Claire M Cannon, Janeen H Trembley, Betsy T Kren, Gretchen M Unger, M Gerard O'Sullivan, Ingrid Cornax, Jaime F Modiano, Khalil Ahmed
OBJECTIVE To investigate protein kinase CK2 (CK2) expression in squamous cell carcinoma (SCC) of cats and to examine effects of CK2 downregulation on in vitro apoptosis and viability in SCC. SAMPLE Biopsy specimens of oral mucosa and testis and blood samples from clinically normal cats, biopsy specimens of oral SCC from cats, and feline SCC (SCCF1) and mammary gland carcinoma (K12) cell lines. PROCEDURES Immunohistochemical labeling for CK2α was performed on biopsy specimens. Sequences of the CK2α subunit gene and CK2α' subunit gene in feline blood and feline cancer cell lines were determined by use of PCR and reverse-transcription PCR assays followed by direct Sanger sequencing...
August 2017: American Journal of Veterinary Research
https://www.readbyqxmd.com/read/28698370/g9a-coordinates-with-the-rpa-complex-to-promote-dna-damage-repair-and-cell-survival
#14
Qiaoyan Yang, Qian Zhu, Xiaopeng Lu, Yipeng Du, Linlin Cao, Changchun Shen, Tianyun Hou, Meiting Li, Zhiming Li, Chaohua Liu, Di Wu, Xingzhi Xu, Lina Wang, Haiying Wang, Ying Zhao, Yang Yang, Wei-Guo Zhu
Histone methyltransferase G9a has critical roles in promoting cancer-cell growth and gene suppression, but whether it is also associated with the DNA damage response is rarely studied. Here, we report that loss of G9a impairs DNA damage repair and enhances the sensitivity of cancer cells to radiation and chemotherapeutics. In response to DNA double-strand breaks (DSBs), G9a is phosphorylated at serine 211 by casein kinase 2 (CK2) and recruited to chromatin. The chromatin-enriched G9a can then directly interact with replication protein A (RPA) and promote loading of the RPA and Rad51 recombinase to DSBs...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28683323/identification-of-a-druggable-pathway-controlling-glioblastoma-invasiveness
#15
Nora Pencheva, Mark C de Gooijer, Daniel J Vis, Lodewyk F A Wessels, Tom Würdinger, Olaf van Tellingen, René Bernards
Diffuse and uncontrollable brain invasion is a hallmark of glioblastoma (GBM), but its mechanism is understood poorly. We developed a 3D ex vivo organotypic model to study GBM invasion. We demonstrate that invading GBM cells upregulate a network of extracellular matrix (ECM) components, including multiple collagens, whose expression correlates strongly with grade and clinical outcome. We identify interferon regulatory factor 3 (IRF3) as a transcriptional repressor of ECM factors and show that IRF3 acts as a suppressor of GBM invasion...
July 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28674151/kinase-activity-ranking-using-phosphoproteomics-data-karp-quantifies-the-contribution-of-protein-kinases-to-the-regulation-of-cell-viability
#16
Edmund H Wilkes, Pedro Casado, Vinothini Rajeeve, Pedro R Cutillas
Cell survival is regulated by a signaling network driven by the activity of protein kinases; however, determining the contribution that each kinase in the network makes to such regulation remains challenging. Here, we report a computational approach that uses mass spectrometry-based phosphoproteomics data to rank protein kinases based on their contribution to cell regulation. We found that the scores returned by this algorithm, which we have termed kinase activity ranking using phosphoproteomics data (KARP), were a quantitative measure of the contribution that individual kinases make to the signaling output...
September 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28672764/interaction-of-tubulin-and-protein-kinase-ck2-in-trypanosoma-equiperdum
#17
Beatriz E Boscán, Graciela L Uzcanga, Maritza Calabokis, Rocío Camargo, Frank Aponte, José Bubis
A polypeptide band with an apparent molecular weight of 55,000 was phosphorylated in vitro in whole-cell lysates of Trypanosoma equiperdum. This band corresponds to tubulin as demonstrated by immunoprecipitation of the phosphorylated polypeptide from T. equiperdum extracts when anti-α and anti-β tubulin monoclonal antibodies were employed. A parasite protein kinase CK2 was in charge of modifying tubulin given that common mammalian CK2 inhibitors such as emodin and GTP, hindered the phosphorylation of tubulin and exogenously added casein...
June 27, 2017: Zeitschrift Für Naturforschung. C, A Journal of Biosciences
https://www.readbyqxmd.com/read/28671992/signaling-pathways-induced-by-serine-proteases-to-increase-intestinal-epithelial-barrier-function
#18
Kelcie A Lahey, Natalie J Ronaghan, Judie Shang, Sébastien P Dion, Antoine Désilets, Richard Leduc, Wallace K MacNaughton
Changes in barrier function of the gastrointestinal tract are thought to contribute to the inflammatory bowel diseases Crohn's disease and ulcerative colitis. Previous work in our lab demonstrated that apical exposure of intestinal epithelial cell lines to serine proteases results in an increase in transepithelial electrical resistance (TER). However, the underlying mechanisms governing this response are unclear. We aimed to determine the requirement for proteolytic activity, epidermal growth factor receptor (EGFR) activation, and downstream intracellular signaling in initiating and maintaining enhanced barrier function following protease treatment using a canine intestinal epithelial cell line (SCBN)...
2017: PloS One
https://www.readbyqxmd.com/read/28649667/impact-of-protein-kinase-ck2-inhibitors-on-proliferation-and-differentiation-of-neural-stem-cells
#19
Melanie Bender, Lisa Schwind, David Grundmann, Monika Martin, Markus Klotz, Claudia Götz, Mathias Montenarh, Karl-Herbert Schäfer
BACKGROUND: Protein kinases play central roles in cell and tissue development. Protein kinase CK2, an ubiquitously expressed serine/threonine kinase has severe impacts on embryo- and spermatogenesis. Since its role in neurogenesis has so far only been investigated in very few studies, we analysed the role of CK2 in neural stem cells by using two specific inhibitors. METHODS: Neural stem cells were isolated from the subventricular zone of neonatal mice, using a neurosphere approach...
June 2017: Heliyon
https://www.readbyqxmd.com/read/28623166/casein-kinase-ii-ck2-glycogen-synthase-kinase-3-gsk-3-and-ikaros-mediated-regulation-of-leukemia
#20
REVIEW
Chandrika Gowda, Mario Soliman, Malika Kapadia, Yali Ding, Kimberly Payne, Sinisa Dovat
Signaling networks that regulate cellular proliferation often involve complex interactions between several signaling pathways. In this manuscript we review the crosstalk between the Casein Kinase II (CK2) and Glycogen Synthase Kinase-3 (GSK-3) pathways that plays a critical role in the regulation of cellular proliferation in leukemia. Both CK2 and GSK-3 are potential targets for anti-leukemia treatment. Previously published data suggest that CK2 and GSK-3 act synergistically to promote the phosphatidylinositol-3 kinase (PI3K) pathway via phosphorylation of PTEN...
June 13, 2017: Advances in Biological Regulation
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