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Ck2 casein kinase

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https://www.readbyqxmd.com/read/28332063/decreased-interaction-between-zo-1-and-occludin-is-involved-in-alteration-of-tight-junctions-in-transplanted-epiphora-submandibular-glands
#1
Chong Ding, Xin Cong, Xue-Ming Zhang, Sheng-Lin Li, Li-Ling Wu, Guang-Yan Yu
Tight junctions (TJs) in salivary epithelium play an important role in regulating saliva secretion. Autologous transplantation of submandibular glands (SMGs) is an effective method to treat severe dry eye syndrome. However, epiphora occurs in some patients 6 months after transplantation. We previously found that the acinar TJs are enlarged in rabbit SMGs after long-term transplantation, but the exact TJ components involved in the epiphora are still unknown. Here, we found that the mRNA and protein expression of ZO-1 and occludin were increased in the transplanted SMGs obtained from epiphora patients, while other TJs were unchanged...
March 22, 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/28288821/reversal-of-cisplatin-resistance-in-human-gastric-cancer-cells-by-a-wogonin-conjugated-pt-iv-prodrug-via-attenuating-casein-kinase-2-mediated-nuclear-factor-%C3%AE%C2%BAb-pathways
#2
Feihong Chen, Xiaodong Qin, Gang Xu, Shaohua Gou, Xiufeng Jin
Pt(IV) prodrugs, with two additional coordination sites in contrast to Pt(II) drugs, have been actively studied nowadays, for they can perform well in enhancing the accumulation and retention of the corresponding Pt(II) drugs in cancer cells. Our designed Pt(II) drug, DN604, was recently found to exhibit significant anticancer activity and low toxicity. While, wogonin, a naturally O-methylated flavones, has been widely investigated for its tumor therapeutic potential. Thus, two Pt(IV)-based prodrugs were derived by addition of a wogonin unit to the axial position of DN604 and its analogue DN603 via a linker group...
March 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28282370/tor1-and-ck2-kinases-control-a-switch-between-alternative-ribosome-biogenesis-pathways-in-a-growth-dependent-manner
#3
Isabelle C Kos-Braun, Ilona Jung, Martin Koš
Ribosome biogenesis is a major energy-consuming process in the cell that has to be rapidly down-regulated in response to stress or nutrient depletion. The target of rapamycin 1 (Tor1) pathway regulates synthesis of ribosomal RNA (rRNA) at the level of transcription initiation. It remains unclear whether ribosome biogenesis is also controlled directly at the posttranscriptional level. We show that Tor1 and casein kinase 2 (CK2) kinases regulate a rapid switch between a productive and a non-productive pre-rRNA processing pathways in yeast...
March 2017: PLoS Biology
https://www.readbyqxmd.com/read/28237649/protein-kinase-ck2%C3%AE-catalytic-subunit-ameliorates-diabetic-renal-inflammatory-fibrosis-via-nf-%C3%AE%C2%BAb-signaling-pathway
#4
Junying Huang, Zhiquan Chen, Jie Li, Qiuhong Chen, Jingyan Li, Wenyan Gong, Jiani Huang, Peiqing Liu, Heqing Huang
Activation of casein kinase 2 (CK2) is closely linked to the body disturbance of carbohydrate metabolism and inflammatory reaction. The renal chronic inflammatory reaction in the setting of diabetes is one of the important hallmarks of diabetic renal fibrosis. However, it remains unknown whether CK2 influences the process of diabetic renal fibrosis. The current study is aimed to investigate if CK2α ameliorates renal inflammatory fibrosis in diabetes via NF-κB pathway. To explore potential regulatory mechanism of CK2α, the expression and activity of CK2α, which were studied by plasmid transfection, selective inhibitor, small-interfering RNA (siRNA) and adenovirus infection in vitro or in vivo, were analyzed by means of western blotting (WB), dual luciferase reporter assay and electrophoretic mobility shift assay (EMSA)...
February 22, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28230762/the-development-of-ck2-inhibitors-from-traditional-pharmacology-to-in-silico-rational-drug-design
#5
REVIEW
Giorgio Cozza
Casein kinase II (CK2) is an ubiquitous and pleiotropic serine/threonine protein kinase able to phosphorylate hundreds of substrates. Being implicated in several human diseases, from neurodegeneration to cancer, the biological roles of CK2 have been intensively studied. Upregulation of CK2 has been shown to be critical to tumor progression, making this kinase an attractive target for cancer therapy. Several CK2 inhibitors have been developed so far, the first being discovered by "trial and error testing". In the last decade, the development of in silico rational drug design has prompted the discovery, de novo design and optimization of several CK2 inhibitors, active in the low nanomolar range...
February 20, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28223413/transcriptional-activation-of-lipogenesis-by-insulin-requires-phosphorylation-of-med17-by-ck2
#6
Jose A Viscarra, Yuhui Wang, Il-Hwa Hong, Hei Sook Sul
De novo lipogenesis is precisely regulated by nutritional and hormonal conditions. The genes encoding various enzymes involved in this process, such as fatty acid synthase (FASN), are transcriptionally activated in response to insulin. We showed that USF1, a key transcription factor for FASN activation, directly interacted with the Mediator subunit MED17 at the FASN promoter. This interaction recruited Mediator, which can bring POL II and other general transcription machinery to the complex. Moreover, we showed that MED17 was phosphorylated at Ser(53) by casein kinase 2 (CK2) in the livers of fed mice or insulin-stimulated hepatocytes, but not in the livers of fasted mice or untreated hepatocytes...
February 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28196025/autophagy-induced-by-cx-4945-a-casein-kinase-2-inhibitor-enhances-apoptosis-in-pancreatic-cancer-cell-lines
#7
Dae Wook Hwang, Kwang Sup So, Song Cheol Kim, Kwang-Min Park, Young-Joo Lee, Sun-Whe Kim, Chang-Min Choi, Jin Kyung Rho, Yun Jung Choi, Jae Cheol Lee
OBJECTIVES: Pancreatic cancer is the most lethal malignancy with only a few effective chemotherapeutic drugs. Because the inhibition of casein kinase 2 (CK2) has been reported as a novel therapeutic strategy for many cancers, we investigated the effects of CK2 inhibitors in pancreatic cancer cell lines. METHODS: The BxPC3, 8902, MIA PaCa-2 human pancreatic cancer cell lines, and CX-4945, a novel CK2 inhibitor, were used. Autophagy was analyzed by acridine orange staining, fluorescence microscope detection of punctuate patterns of GFP-tagged LC3 and immunoblotting for LC3...
April 2017: Pancreas
https://www.readbyqxmd.com/read/28152014/apigenin-selective-ck2-inhibitor-increases-ikaros-expression-and-improves-t-cell-homeostasis-and-function-in-murine-pancreatic-cancer
#8
Nadine Nelson, Karoly Szekeres, Cristina Iclozan, Ivannie Ortiz Rivera, Andrew McGill, Gbemisola Johnson, Onyekachi Nwogu, Tomar Ghansah
Pancreatic cancer (PC) evades immune destruction by favoring the development of regulatory T cells (Tregs) that inhibit effector T cells. The transcription factor Ikaros is critical for lymphocyte development, especially T cells. We have previously shown that downregulation of Ikaros occurs as a result of its protein degradation by the ubiquitin-proteasome system in our Panc02 tumor-bearing (TB) mouse model. Mechanistically, we observed a deregulation in the balance between Casein Kinase II (CK2) and protein phosphatase 1 (PP1), which suggested that increased CK2 activity is responsible for regulating Ikaros' stability in our model...
2017: PloS One
https://www.readbyqxmd.com/read/28130399/constitutive-phosphorylation-of-stat3-by-the-ck2-blnk-cd5-complex
#9
Uri Rozovski, David M Harris, Ping Li, Zhiming Liu, Preetesh Jain, Ivo Veletic, Alessandra Ferrajoli, Jan Burger, Susan O'Brien, Prithviraj Bose, Philip Thompson, Nitin Jain, William Wierda, Michael J Keating, Zeev Estrov
In chronic lymphocytic leukemia (CLL), STAT3 is constitutively phosphorylated on serine 727 and plays a role in the pathobiology of CLL. However, what induces constitutive phosphorylation of STAT3 is currently unknown. Mass spectrometry was used to identify casein kinase 2 (CK2), a serine/threonine kinase that co-immunoprecipitated with serine phosphorylated STAT3 (pSTAT3). Furthermore, activated CK2 incubated with recombinant STAT3 induced phosphorylation of STAT3 on serine 727. Although STAT3 and CK2 are present in normal B- and T-cells, STAT3 is not constitutively phosphorylated in these cells...
January 27, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28117670/exploring-the-ck2-paradox-restless-dangerous-dispensable
#10
REVIEW
Cinzia Franchin, Christian Borgo, Silvia Zaramella, Luca Cesaro, Giorgio Arrigoni, Mauro Salvi, Lorenzo A Pinna
The history of protein kinase CK2 is crowded with paradoxes and unanticipated findings. Named after a protein (casein) that is not among its physiological substrates, CK2 remained in search of its targets for more than two decades after its discovery in 1954, but it later came to be one of the most pleiotropic protein kinases. Being active in the absence of phosphorylation and/or specific stimuli, it looks unsuitable to participate in signaling cascades, but its "lateral" implication in a variety of signaling pathways is now soundly documented...
January 20, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28105499/cx4945-suppresses-the-growth-of-castration-resistant-prostate-cancer-cells-by-reducing-ar-v7-expression
#11
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/28089218/nkg2d-signaling-the-immune-subversive-side-of-hdac3
#12
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.
March 2017: Trends in Immunology
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
#13
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/28052864/lipopolysaccharide-inhibits-colonic-biotin-uptake-via-interference-with-membrane-expression-of-its-transporter-a-role-for-casein-kinase-2-mediated-pathway
#14
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/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...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28027904/esculentoside-a-suppresses-lipopolysaccharide-induced-pro-inflammatory-molecule-production-partially-by-casein-kinase-2
#16
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/27994036/microhomology-mediated-end-joining-is-activated-in-irradiated-human-cells-due-to-phosphorylation-dependent-formation-of-the-xrcc1-repair-complex
#17
Arijit Dutta, Bradley Eckelmann, Sanjay Adhikari, Kazi Mokim Ahmed, Shiladitya Sengupta, Arvind Pandey, Pavana M Hegde, Miaw-Sheue Tsai, John A Tainer, Michael Weinfeld, Muralidhar L Hegde, Sankar Mitra
Microhomology-mediated end joining (MMEJ), an error-prone pathway for DNA double-strand break (DSB) repair, is implicated in genomic rearrangement and oncogenic transformation; however, its contribution to repair of radiation-induced DSBs has not been characterized. We used recircularization of a linearized plasmid with 3'-P-blocked termini, mimicking those at X-ray-induced strand breaks, to recapitulate DSB repair via MMEJ or nonhomologous end-joining (NHEJ). Sequence analysis of the circularized plasmids allowed measurement of relative activity of MMEJ versus NHEJ...
December 19, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27965149/involvement-of-brd4-in-different-steps-of-the-papillomavirus-life-cycle
#18
REVIEW
Thomas Iftner, Juliane Haedicke-Jarboui, Shwu-Yuan Wu, Cheng-Ming Chiang
Bromodomain-containing protein 4 (Brd4) is a cellular chromatin-binding factor and transcriptional regulator that recruits sequence-specific transcription factors and chromatin modulators to control target gene transcription. Papillomaviruses (PVs) have evolved to hijack Brd4's activity in order to create a facilitating environment for the viral life cycle. Brd4, in association with the major viral regulatory protein E2, is involved in multiple steps of the PV life cycle including replication initiation, viral gene transcription, and viral genome segregation and maintenance...
March 2, 2017: Virus Research
https://www.readbyqxmd.com/read/27959425/inhibition-of-casein-kinase%C3%A2-2-prevents-growth-of-human-osteosarcoma
#19
Kengo Takahashi, Takao Setoguchi, Arisa Tsuru, Yoshinobu Saitoh, Satoshi Nagano, Yasuhiro Ishidou, Shingo Maeda, Tatsuhiko Furukawa, Setsuro Komiya
High-dose chemotherapy and surgical treatment have improved the prognosis of osteosarcoma. However, more than 20% of patients with osteosarcoma still have a poor prognosis. We investigated the expression and function of casein kinase 2 (CK2) in osteosarcoma growth. We then examined the effects of CX-4945, a CK2 inhibitor, on osteosarcoma growth in vitro and in vivo to apply our findings to the clinical setting. We examined the expression of CK2α and CK2β by western blot analysis, and performed WST-1 assays using CK2α and CK2β siRNA or CX-4945...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/27957526/mammalian-fmrp-s499-is-phosphorylated-by-ck2-and-promotes-secondary-phosphorylation-of-fmrp
#20
Christopher M Bartley, Rachel A O'Keefe, Anna Blice-Baum, Mihaela-Rita Mihailescu, Xuan Gong, Laura Miyares, Esra Karaca, Angélique Bordey
The fragile X mental retardation protein (FMRP) is an mRNA-binding regulator of protein translation that associates with 4-6% of brain transcripts and is central to neurodevelopment. Autism risk genes' transcripts are overrepresented among FMRP-binding mRNAs, and FMRP loss-of-function mutations are responsible for fragile X syndrome, the most common cause of monogenetic autism. It is thought that FMRP-dependent translational repression is governed by the phosphorylation of serine residue 499 (S499). However, recent evidence suggests that S499 phosphorylation is not modulated by metabotropic glutamate receptor class I (mGluR-I) or protein phosphatase 2A (PP2A), two molecules shown to regulate FMRP translational repression...
November 2016: ENeuro
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