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Casein kinase 1

Hao Zhou, Pingjun Zhu, Jin Wang, Hong Zhu, Jun Ren, Yundai Chen
Disturbed mitochondrial homeostasis contributes to the pathogenesis of cardiac ischemia reperfusion (IR) injury, although the underlying mechanism remains elusive. Here, we demonstrated that casein kinase 2α (CK2α) was upregulated following acute cardiac IR injury. Increased CK2α was shown to be instrumental to mitochondrial damage, cardiomyocyte death, infarction area expansion and cardiac dysfunction, whereas cardiac-specific CK2α knockout (CK2αCKO ) mice were protected against IR injury and mitochondrial damage...
March 14, 2018: Cell Death and Differentiation
Katy Billot, Charlène Coquil, Benoit Villiers, Béatrice Josselin-Foll, Nathalie Desban, Claire Delehouze, Nassima Oumata, Yannick Le Meur, Alessandra Boletta, Thomas Weimbs, Melanie Grosch, Ralph Witzgall, Sophie Saunier, Evelyne Fischer, Marco Pontoglio, Alain Fautrel, Michal Mrug, Darren Paul Wallace, Pamela V Tran, Marie Trudel, Nikolay O Bukanov, Oxana Ibraghimov-Beskrovnaya, Laurent Meijer
Following the discovery of (R)-roscovitine's beneficial effects in three polycystic kidney disease (PKD) mouse models, cyclin-dependent kinases (CDKs) inhibitors are investigated as potential treatments. We have used various affinity chromatography approaches to identify the molecular targets of roscovitine and its more potent analogue (S)-CR8 in human and murine polycystic kidneys. These methods revealed casein kinases 1 (CK1) as additional targets of the two drugs. CK1ε expression at the mRNA and protein levels is enhanced in polycystic kidneys of 11 different PKD mouse models, as well as in human polycystic kidneys...
March 14, 2018: American Journal of Physiology. Renal Physiology
Ondrej Benek, Lukas Hroch, Laura Aitken, Frank Gunn-Moore, Lucie Vinklarova, Kamil Kuca, Daniel I Perez, Concepcion Perez, Ana Martinez, Zdenek Fisar, Kamil Musilek
Several neurodegenerative disorders including Alzheimer's disease (AD) have been connected with deregulation of casein kinase 1 (CK1) activity. Inhibition of CK1 therefore presents a potential therapeutic strategy against such pathologies. Recently, novel class of CK1-specific inhibitors with N-(benzo[d]thiazol-2-yl)-2-phenylacetamide structural scaffold has been discovered. 1-(benzo[d]thiazol-2-yl)-3-phenylureas, on the other hand, are known inhibitors amyloid-beta binding alcohol dehydrogenase (ABAD), an enzyme also involved in pathophysiology of AD...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
Polyxeni Bozatzi, Kevin S Dingwell, Kevin Zl Wu, Fay Cooper, Timothy D Cummins, Luke D Hutchinson, Janis Vogt, Nicola T Wood, Thomas J Macartney, Joby Varghese, Robert Gourlay, David G Campbell, James C Smith, Gopal P Sapkota
The BMP and Wnt signalling pathways determine axis specification during embryonic development. Our previous work has shown that PAWS1 (also known as FAM83G) interacts with SMAD1 and modulates BMP signalling. Here, surprisingly, we show that overexpression of PAWS1 in Xenopus embryos activates Wnt signalling and causes complete axis duplication. Consistent with these observations in Xenopus , Wnt signalling is diminished in U2OS osteosarcoma cells lacking PAWS1, while BMP signalling is unaffected. We show that PAWS1 interacts and co-localises with the α isoform of casein kinase 1 (CK1), and that PAWS1 mutations incapable of binding CK1 fail both to activate Wnt signalling and to elicit axis duplication in Xenopus embryos...
March 7, 2018: EMBO Reports
Jordi Vilardell, Cristina Girardi, Oriano Marin, Giorgio Cozza, Lorenzo A Pinna, Maria Ruzzene
CK2 is a pleiotropic S/T protein kinase (formerly known as casein kinase 2) which is attracting increasing interest as therapeutic target, and the identification of its substrates is a crucial step in determining its involvement in different pathological conditions. We recently found that S131 of Akt2 (homologous to the well established CK2 target S129 of Akt1) is not phosphorylated by CK2 either in vitro or in vivo, although the consensus sequence recognized by CK2 (S/T-x-x-E/D/pS/pT) is conserved in it. Here, by exploiting synthetic peptides, in cell transfection experiments, and computational analysis, we show that a single sequence element, a T at position n+1, hampers phosphorylation, causing an α-helix structure organization which prevents the recognition of its own consensus by CK2...
2018: PloS One
Howard A Burris, Ian W Flinn, Manish R Patel, Timothy S Fenske, Changchun Deng, Danielle M Brander, Martin Gutierrez, James H Essell, John G Kuhn, Hari P Miskin, Peter Sportelli, Michael S Weiss, Swaroop Vakkalanka, Michael R Savona, Owen A O'Connor
BACKGROUND: Umbralisib (TGR-1202) is a novel next-generation inhibitor of phosphatidylinositol 3-kinase (PI3K) isoform p110δ (PI3Kδ), which is structurally distinct from other PI3Kδ inhibitors and shows improved isoform selectivity. Umbralisib also uniquely inhibits casein kinase-1ε, a major regulator of protein translation. The aim of this first-in-human phase 1 study was to establish the safety and preliminary activity profile of umbralisib in patients with haematological malignancies...
February 20, 2018: Lancet Oncology
Paula M De Angelis, Aasa R Schjølberg, Juliana B Hughes, Henrik S Huitfeldt, Solveig Norheim Andersen, Anne Carine Østvold
Background: The colon and rectum are continuously exposed to oxidative stress that generates reactive oxygen species, which are a major cause of DNA double-strand breaks (DSB). Furthermore, chronic inflammatory diseases such as ulcerative colitis (UC) are characterized by an excess of reactive nitrogen species that can also lead to DNA double-strand breakage and genomic instability. We investigated the expression of the nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) protein in UC and sporadic colorectal cancer (CRC) due to its involvement in both DNA double-strand break repair and inflammatory signaling...
February 15, 2018: Inflammatory Bowel Diseases
Xiao-Lin Shi, Bo-Cheng Liang, Peng Wu, Bo Wang, Zhen-Yu Shi, Ling-Cheng Kong, Jian-Liang Yao, Jun-Jun Huang, Chun-Wen Li
OBJECTIVE: To explore the effects and related mechanisms of total flavone of epimedium treatment(TFE)on primary callus for mation in ovariectomized rats. METHODS: Forty male SD rats weighted from 209 to 246 g and aged 6 to 8 weeks were selected. Six weeks after ovariectomy a femur fracture model with middiaphyseal segment fracture was established, estimated and randomly divided into TFE group (150 mg·kg⁻¹·d⁻¹) and control group(received saline). HE staining was used to evaluate the morphologic difference of primary callus during the bone callus healing between these two groups...
August 25, 2017: Zhongguo Gu Shang, China Journal of Orthopaedics and Traumatology
Qingquan Ma, Shengdi Hu, Makoto Bannai, Guoyao Wu
Milk is an important food for mammalian neonates, but its insufficient production is a nutritional problem for humans and other animals. Recent studies indicate that dietary supplementation with L-arginine (Arg) increases milk production in mammals, including sows, rabbits, and cows. However, the underlying molecular mechanisms remain largely unknown. The present study was conducted with porcine mammary epithelial cells (PMECs) to test the hypothesis that Arg enhances milk protein synthesis via activation of the mechanistic target of rapamycin (mTOR) cell signaling...
February 12, 2018: Amino Acids
Shukuan Ling, Yuheng Li, Guohui Zhong, Yongjun Zheng, Qing Xu, Dingsheng Zhao, Weijia Sun, Xiaoyan Jin, Hongxing Li, Jianwei Li, Huiyuan Sun, Dengchao Cao, Jinping Song, Caizhi Liu, Xinxin Yuan, Xiaorui Wu, Yinlong Zhao, Zizhong Liu, Qi Li, Yingxian Li
Human cardiovascular system has adapted to Earth's gravity of 1G. The microgravity during space flight can induce cardiac remodeling and decline of cardiac function. At present, the mechanism of cardiac remodeling induced by microgravity remains to be disclosed. Casein kinase-2 interacting protein-1 (CKIP-1) is an important inhibitor of pressure-overload induced cardiac remodeling by decreasing the phosphorylation level of HDAC4. However, the role of CKIP-1 in the cardiac remodeling induced by microgravity is unknown...
2018: Frontiers in Physiology
Xuehui Hong, He Huang, Xingfeng Qiu, Zhijie Ding, Xing Feng, Yuekun Zhu, Huiqin Zhuo, Jingjing Hou, Jiabao Zhao, Wangyu Cai, Ruihua Sha, Xinya Hong, Yongxiang Li, Hongjiang Song, Zhiyong Zhang
RIOK1 has recently been shown to play important roles in cancers, but its posttranslational regulation is largely unknown. Here we report that RIOK1 is methylated at K411 by SETD7 methyltransferase and that lysine-specific demethylase 1 (LSD1) reverses its methylation. The mutated RIOK1 (K411R) that cannot be methylated exhibits a longer half-life than does the methylated RIOK1. FBXO6 specifically interacts with K411-methylated RIOK1 through its FBA domain to induce RIOK1 ubiquitination. Casein kinase 2 (CK2) phosphorylates RIOK1 at T410, which stabilizes RIOK1 by antagonizing K411 methylation and impeding the recruitment of FBXO6 to RIOK1...
January 31, 2018: ELife
Abdelhamid Nacereddine, Andre Bollacke, Eszter Róka, Christelle Marminon, Zouhair Bouaziz, Ferenc Fenyvesi, Ildikó Katalin Bácskay, Joachim Jose, Florent Perret, Marc Le Borgne
Since the approval of imatinib in 2001, kinase inhibitors have revolutionized cancer therapies. Inside this family of phosphotransferases, casein kinase 2 (CK2) is of great interest and numerous scaffolds have been investigated to design CK2 inhibitors. Recently, functionalized indeno[1,2-b]indoles have been revealed to have high potency against human cancer cell lines such as MCF-7 breast carcinoma and A-427 lung carcinoma. 4-Methoxy-5-isopropyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione (THN7), identified as a potent inhibitor of CK2 (IC50 = 71 nM), was selected for an encapsulation study in order to evaluate its antiproliferative activity as THN7-loaded cyclodextrin nanoparticles...
January 26, 2018: Pharmaceuticals
Jeng-Shyan Deng, Jui-Shu Chang, Jung-Chun Liao, Wei Chao, Ming-Ming Lee, Chien-Hua Cheng, Guan-Jhong Huang
BACKGROUND: Cancer cell metastasis involving multi-step procedures and cytophysiological property changes may make difficult in the clinical management and death rate increasing. RESULTS: In this study, we first observed that ethyl acetate fraction of Actinidia callosa var. callosa (EAAC) carry out a dose-dependent inhibitory effect without cytotoxicity on the mobility and invasion of highly metastatic SK-Hep1 cells. To investigate the EAAC in cancer metastasis, SK-Hep1 cells were treated with EAAC at various concentrations and then subjected to gelatin zymography, casein zymography and western blot to study the impacts of EAAC on metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1/2 (TIMP-1/2), respectively...
January 22, 2018: Botanical Studies (Taipei, Taiwan)
Chuan Xia, Jennifer J Wolf, Madhuvanthi Vijayan, Caleb J Studstill, Wenjun Ma, Bumsuk Hahm
Although influenza A virus (IAV) evades cellular defense systems to effectively propagate in the host, the viral immune evasive mechanisms are incompletely understood. Our recent data showed that hemagglutinin (HA) of IAV induces degradation of type I IFN receptor 1 (IFNAR1). Here, we demonstrate that IAV HA induces degradation of type II IFN (IFN-γ) receptor 1 (IFNGR1) as well as IFNAR1 via casein kinase 1α (CK1α), resulting in the impairment of cellular responsiveness to both type I and II IFNs. IAV infection or transient HA expression induced degradation of both IFNGR1 and IFNAR1, whereas HA gene-deficient IAV failed to downregulate the receptors...
January 17, 2018: Journal of Virology
Qing-Bo Yu, Tuan-Tuan Zhao, Lin-Shan Ye, Ling Cheng, Ying-Qian Wu, Chao Huang, Zhong-Nan Yang
In higher plant chloroplasts, the plastid-encoded RNA polymerase (PEP) consists of four catalytic subunits and numerous nuclear-encoded accessory proteins, including pTAC10, an S1-domain-containing protein. In this study, pTAC10 knockout lines were characterized. Two ptac10 mutants had an albino phenotype and severely impaired chloroplast development. The pTAC10 genomic sequence fused to a four-tandem MYC tag driven by its own promoter functionally complemented the ptac10-1 mutant phenotype. pTAC10 was present in both the chloroplast stroma and thylakoids...
January 12, 2018: Photosynthesis Research
Qiliang Liu, Yong Guo, Yang Wang, Xianqiong Zou, Zhixiong Yan
Casein kinase 2-interacting protein 1 (CKIP-1) is a negative regulator for bone formation. Previously, using bioinformatics analysis, CKIP‑1 has been predicted to serve the role of target gene of miR‑98‑5p. In the present study, the potential role of miR‑98‑5p in regulating osteoblast differentiation through CKIP‑1 was investigated. Following pre‑treatment with microRNA (miR)‑98‑5p agomir or miR‑98‑5p antagomir, MC3T3‑E1 cells were cultured in an osteoinductive medium. Subsequently, the expression of miR‑98‑5p, CKIP‑1 and levels of osteoblast differentiation markers, including alkaline phosphatase, matrix mineralization, osteocaicin, collagen type I, runt‑related transcription factor 2 and osteopontin were assayed...
January 9, 2018: Molecular Medicine Reports
Pavlina Janovska, Jan Verner, Jiri Kohoutek, Lenka Bryjova, Michaela Gregorova, Marta Dzimkova, Hana Skabrahova, Tomasz Radaszkiewicz, Petra Ovesna, Olga Vondalova Blanarova, Tereza Nemcova, Zuzana Hoferova, Katerina Vasickova, Lucie Smyckova, Alexander Egle, Sarka Pavlova, Lucie Poppova, Karla Plevova, Sarka Pospisilova, Vitezslav Bryja
Casein kinase (CK) 1δ/ε is a key component of non-canonical Wnt signaling pathways, which were shown previously to drive pathogenesis of chronic lymphocytic leukemia (CLL). In this study we investigated thoroughly the effects of CK1δ/ε inhibition on the primary CLL cells and analyzed the therapeutic potential in vivo using two murine model systems based on the Eµ-TCL1-induced leukemia (syngeneic adoptive transfer model and spontaneous disease development), which resemble closely the human CLL. We can demonstrate that CK1δ/ε inhibitor PF-670462 significantly blocks microenvironmental interactions - chemotaxis, invasion and communication with stromal cells in primary CLL cells in all major subtypes of CLL...
January 9, 2018: Blood
Rui Wang, Yuxing Cai, Baoping Zhang, Zhengxia Wu
The present study aimed to perform screening of a gene signature for the discrimination and prognostic prediction of stage I and II lung squamous carcinoma. A microarray meta‑analysis was performed to identify differentially expressed genes (DEGs) between stage I and II lung squamous carcinoma samples in seven microarray datasets collected from the Gene Expression Omnibus database via the MetaQC and MetaDE package in R. The important DEGs were selected according to the betweenness centrality value of the protein‑protein interaction (PPI) network...
December 19, 2017: International Journal of Molecular Medicine
Andrea Polo, Sakshi Singh, Anna Crispo, Marilina Russo, Aldo Giudice, Maurizio Montella, Giovanni Colonna, Susan Costantini
Network analysis is a useful approach in cancer biology as it provides information regarding the genes and proteins. In our previous study, a network analysis was performed on dysregulated genes in HepG2 cells, a hepatoblastoma cell line that lacks the viral infection, compared with normal hepatocytes, identifying the presence of 26 HUB genes. The present study aimed to identify whether these previously identified HUB genes participate in the network that controls the human circadian rhythms. The results of the present study demonstrated that 20/26 HUB genes were associated with the metabolic processes that control human circadian rhythms, which supports the hypothesis that a number of cancer types are dependent from circadian cycles...
December 2017: Oncology Letters
Wenyan Gong, Zhiquan Chen, Yezi Zou, Lei Zhang, Junying Huang, Peiqing Liu, Heqing Huang
Our previous study indicated that Casein kinase 2 interacting protein-1 (CKIP-1) could promote the activation of the nuclear factor E2-related factor 2 (Nrf2)/ antioxidant response element (ARE) pathway, playing a significant role in inhibiting the fibrosis of diabetic nephropathy (DN). However, the underlying mechanism is still unknown. Here, we investigated whether CKIP-1 affects the polyubiquitination of Nrf2 and its cytosolic inhibitor kelch like ECH-associated protein 1 (Keap1) via mediating Smad ubiquitylation regulatory factor-1 (Smurf1) to promote the activation of the Nrf2/ARE signaling and resist high glucose (HG)-induced renal fibrosis in glomerular mesangial cells (GMCs) and diabetic mice kidneys...
February 1, 2018: Free Radical Biology & Medicine
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