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https://www.readbyqxmd.com/read/29214152/identification-of-candidate-casein-kinase-2-substrates-in-mitosis-by-quantitative-phosphoproteomics
#1
Scott F Rusin, Mark E Adamo, Arminja N Kettenbach
Protein phosphorylation is a crucial regulatory mechanism that controls many aspects of cellular signaling. Casein kinase 2 (CK2), a constitutively expressed and active kinase, plays key roles in an array of cellular events including transcription and translation, ribosome biogenesis, cell cycle progression, and apoptosis. CK2 is implicated in cancerous transformation and is a therapeutic target in anti-cancer therapy. The specific and selective CK2 ATP competitive inhibitor, CX-4945 (silmitaseratib), is currently in phase 2 clinical trials...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29191835/phosphorylation-of-human-enhancer-filamentation-1-hef1-stimulates-interaction-with-polo-like-kinase-1-leading-to-hef1-localization-to-focal-adhesions
#2
Kyung Ho Lee, Jeong-Ah Hwang, Sun-Ok Kim, Jung Hee Kim, Sang Chul Shin, Eunice EunKyeong Kim, Kyung S Lee, Kunsoo Rhee, Byeong Hwa Jeon, Jeong Kyu Bang, Hyunjoo Cha-Molstad, Nak-Kyun Soung, Jae-Hyuk Jang, Sung-Kyun Ko, Hee Gu Lee, Jong Seog Ahn, Yong Tae Kwon, Bo Yeon Kim
Elevated expression of human enhancer filamentation 1 (HEF1; also known as NEDD9 or Cas-L) is an essential stimulus for the metastatic process of various solid tumors. This process requires HEF1 localization to focal adhesions (FAs). Although the association of HEF1 with FAs is considered to play a role in cancer cell migration, the mechanism targeting HEF1 to FAs remains unclear. Moreover, upregulation of polo-like kinase 1 (Plk1) positively correlates with human cancer metastasis, yet how Plk1 deregulation promotes metastasis remains elusive...
November 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29142273/a-novel-medium-for-enhancing-callus-growth-of-hazel-corylus-avellana-l
#3
Mina Salehi, Ahmad Moieni, Naser Safaie
Paclitaxel is a powerful antimitotic agent with excellent activity against a range of cancers. Hazel has been described as a paclitaxel-producing species among angiosperms. Fast-growing callus is a prerequisite for the success of callus production and then paclitaxel production. Therefore, optimizing the medium culture for enhancing callus growth is a crucial step for paclitaxel production. In this research, Murashige and Skoog (1962) (MS) medium was optimized for improving callus growth of hazel (Corylus avellana L...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29141220/phosphorylation-and-ubiquitination-regulate-protein-phosphatase-5-activity-and-its-prosurvival-role-in-kidney-cancer
#4
Natela Dushukyan, Diana M Dunn, Rebecca A Sager, Mark R Woodford, David R Loiselle, Michael Daneshvar, Alexander J Baker-Williams, John D Chisholm, Andrew W Truman, Cara K Vaughan, Timothy A Haystead, Gennady Bratslavsky, Dimitra Bourboulia, Mehdi Mollapour
The serine/threonine protein phosphatase 5 (PP5) regulates multiple cellular signaling networks. A number of cellular factors, including heat shock protein 90 (Hsp90), promote the activation of PP5. However, it is unclear whether post-translational modifications also influence PP5 phosphatase activity. Here, we show an "on/off switch" mechanism for PP5 regulation. The casein kinase 1δ (CK1δ) phosphorylates T362 in the catalytic domain of PP5, which activates and enhances phosphatase activity independent of Hsp90...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29113166/expression-of-circadian-clock-genes-in-human-colorectal-adenoma-and-carcinoma
#5
Tomoyuki Momma, Hirokazu Okayama, Masaru Saitou, Hidekazu Sugeno, Nobuhiro Yoshimoto, Yuji Takebayashi, Shinji Ohki, Seiichi Takenoshita
Circadian rhythms are fundamental biological systems in most organisms. Epidemiological and animal studies have demonstrated that disruption of circadian rhythms is linked to tumor progression and mammalian tumorigenesis. However, the clinical significance of in situ clock gene expression in precancerous and cancerous colorectal lesions remains unknown. The present study aimed to investigate mRNA transcript levels of circadian clock genes within human colorectal cancer and adenoma tissue sections. Using in situ hybridization, the expression of key clock genes, including period circadian protein homolog (Per) 1 and 2, cryptochrome 1 (Cry1), circadian locomoter output cycles protein kaput (Clock), brain and muscle ARNT-like protein 1 (Bmal1) and casein kinase 1ε (CK1ε) were retrospectively examined in 51 cases of colorectal carcinoma and 10 cases of adenoma...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29104459/effects-of-oral-glutamine-on-inflammatory-and-autophagy-responses-in-cancer-patients-treated-with-abdominal-radiotherapy-a-pilot-randomized-trial
#6
Juan J Ortiz de Urbina, Beatriz San-Miguel, Alfonso Vidal-Casariego, Irene Crespo, Diana I Sánchez, José L Mauriz, Jesús M Culebras, Javier González-Gallego, María J Tuñón
Background and Aims: Abdominal radiotherapy (RT) causes harm to the mid gastrointestinal mucosa by release of pro-inflammatory cytokines and promotes autophagic changes in tumor cells. This study was aimed to measure the effect of glutamine administration on markers of inflammation and autophagy in cancer patients treated with RT. Methods: In this double-blind, randomized, controlled pilot trial 43 patients under abdominal RT diagnosed of pelvic or abdominal malignancies receiving glutamine (30 g/d) or placebo (casein, 30 g/d)...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29069804/progesterone-receptor-membrane-component-1-is-phosphorylated-upon-progestin-treatment-in-breast-cancer-cells
#7
Marina Willibald, Giuliano Bayer, Vanessa Stahlhut, Gereon Poschmann, Kai Stühler, Berthold Gierke, Michael Pawlak, Harald Seeger, Alfred O Mueck, Dieter Niederacher, Tanja Fehm, Hans Neubauer
Menopausal hormone therapy, using estrogen and synthetic progestins, is associated with an increased risk of developing breast cancer. The effect of progestins on breast cells is complex and not yet fully understood. In previous in vitro and in vivo studies, we found different progestins to increase the proliferation of Progesterone Receptor Membrane Component-1 (PGRMC1)-overexpressing MCF7 cells (MCF7/PGRMC1), suggesting a possible role of PGRMC1 in transducing membrane-initiated progestin signals. Understanding the activation mechanism of PGRMC1 by progestins will provide deeper insights into the mode of action of progestins on breast cells and the often-reported phenomenon of elevated breast cancer rates upon progestin-based hormone therapy...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29042609/structural-analysis-of-pim1-kinase-complexes-with-atp-competitive-inhibitors
#8
Jozefina Bogusz, Karol Zrubek, Krzysztof P Rembacz, Przemyslaw Grudnik, Przemyslaw Golik, Malgorzata Romanowska, Benedykt Wladyka, Grzegorz Dubin
PIM1 is an oncogenic kinase overexpressed in a number of cancers where it correlates with poor prognosis. Several studies demonstrated that inhibition of PIM1 activity is an attractive strategy in fighting overexpressing cancers, while distinct structural features of ATP binding pocket make PIM1 an inviting target for the design of selective inhibitors. To facilitate development of specific PIM1 inhibitors, in this study we report three crystal structures of ATP-competitive inhibitors at the ATP binding pocket of PIM1...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29033852/activation-of-casein-kinase-ii-by-gallic-acid-induces-bik-bax-bak-mediated-er-ca-ros-dependent-apoptosis-of-human-oral-cancer-cells
#9
Meng-Liang Lin, Shih-Shun Chen
Induction of the generation of endoplasmic reticulum (ER) calcium (Ca(++))-mediated reactive oxygen species (ROS) by gallic acid (GA) has been implicated in the mitochondrial apoptotic death of human oral cancer (OC) cells, but the molecular mechanism by which GA causes ER Ca(++) release of OC cells to undergo cell death remains unclear. Here, we report that GA-induced phosphorylation of B-cell lymphoma 2 (BCL-2)-interacting killer (BIK) (threonine (Thr) 33/Serine (Ser) 35) and p53 (Ser 15 and Ser 392), Bcl-2-associated x protein (BAX)/BCL-2 antagonist killer 1 (BAK) oligomerization on the ER and mitochondria, rising of cytosolic Ca(+)(+) and ROS, cytochrome c (Cyt c) release from the mitochondria, Ψm loss, and apoptosis were suppressed in cells co-treated with a specific inhibitor of casein kinase II (CK II) (4,5,6,7-tetrabromobenzotriazole)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28945225/oncogenic-ras-induced-ck1%C3%AE-drives-nuclear-foxo-proteolysis
#10
F Zhang, D M Virshup, J K Cheong
Evasion of forkhead box O (FOXO) family of longevity-related transcription factors-mediated growth suppression is necessary to promote cancer development. Since somatic alterations or mutations and transcriptional dysregulation of the FOXO genes are infrequent in human cancers, it remains unclear how these tumour suppressors are eliminated from cancer cells. The protein stability of FOXO3A is regulated by Casein Kinase 1 alpha (CK1α) in an oncogenic RAS-specific manner, but whether this mode of regulation extends to related FOXO family members is unknown...
September 25, 2017: Oncogene
https://www.readbyqxmd.com/read/28918013/mir-135b-stimulates-osteosarcoma-recurrence-and-lung-metastasis-via-notch-and-wnt-%C3%AE-catenin-signaling
#11
Hua Jin, Song Luo, Yun Wang, Chang Liu, Zhenghao Piao, Meng Xu, Wei Guan, Qing Li, Hua Zou, Qun-You Tan, Zhen-Zhou Yang, Yan Wang, Dong Wang, Cheng-Xiong Xu
Cancer stem cells (CSCs) play an important role in osteosarcoma (OS) metastasis and recurrence, and both Wnt/β-catenin and Notch signaling are essential for the development of the biological traits of CSCs. However, the mechanism that underlies the simultaneous hyperactivation of both Wnt/β-catenin and Notch signaling in OS remains unclear. Here, we report that expression of miR-135b correlates with the overall and recurrence-free survival of OS patients, and that miR-135b has an activating effect on both Wnt/β-catenin and Notch signaling...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28877654/nucks-nuclear-elevated-expression-indicates-progression-and-prognosis-of-ovarian-cancer
#12
Ce Shi, Ling Qin, Hongyu Gao, Lina Gu, Chang Yang, Hebing Liu, Tianbo Liu
NUCKS (nuclear, casein kinase, and cyclin-dependent kinase substrate) is implicated in the tumorigenesis of several human malignancies, but its role in ovarian cancer remains unknown. We aim to investigate NUCKS expression and its clinical significance in ovarian cancer. The messenger RNA expression of NUCKS was determined in normal and malignant ovarian tissues using quantitative polymerase chain reaction assay. Immunohistochemistry was applied to detect the status of NUCKS protein expression in 121 ovarian cancer tissues...
September 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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
#13
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/28797931/changes-in-the-gut-microbial-communities-following-addition-of-walnuts-to-the-diet
#14
Lauri O Byerley, Derrick Samuelson, Eugene Blanchard, Meng Luo, Brittany N Lorenzen, Shelia Banks, Monica A Ponder, David A Welsh, Christopher M Taylor
Walnuts are rich in omega-3 fatty acids, phytochemicals and antioxidants making them unique compared to other foods. Consuming walnuts has been associated with health benefits including a reduced risk of heart disease and cancer. Dysbiosis of the gut microbiome has been linked to several chronic diseases. One potential mechanism by which walnuts may exert their health benefit is through modifying the gut microbiome. This study identified the changes in the gut microbial communities that occur following the inclusion of walnuts in the diet...
October 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28780347/nanoscale-observation-of-the-natural-structure-of-milk-fat-globules-and-casein-micelles-in-the-liquid-condition-using-a-scanning-electron-assisted-dielectric-microscopy
#15
Toshihiko Ogura, Tomoko Okada
Recently, aqueous nanoparticles have been used in drug-delivery systems for new type medicines. In particular, milk-casein micelles have been used as drug nanocarriers for targeting cancer cells. Therefore, nanostructure observation of particles and micelles in their native liquid condition is indispensable for analysing their function and mechanisms. However, traditional optical and scanning electron microscopy have difficulty observing the nanostructures of aqueous micelles. Recently, we developed a novel imaging technique called scanning electron-assisted dielectric microscopy (SE-ADM) that enables observation of various biological specimens in water with very little radiation damage and high-contrast imaging without staining or fixation at an 8-nm spatial resolution...
September 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28765774/increase-in-dietary-protein-content-exacerbates-colonic-inflammation-and-tumorigenesis-in-azoxymethane-induced-mouse-colon-carcinogenesis
#16
Ka-Hee Tak, Eunyeong Ahn, Eunjung Kim
BACKGROUND/OBJECTIVE: The incidence of colorectal cancer (CRC) has been attributed to higher intake of fat and protein. However, reports on the relationship between protein intake and CRC are inconsistent, possibly due to the complexity of diet composition. In this study, we addressed a question whether alteration of protein intake is independently associated with colonic inflammation and colon carcinogenesis. MATERIALS/METHODS: Balb/c mice were randomly divided into 4 experimental groups: 20% protein (control, 20P, 20% casein/kg diet), 10% protein (10P, 10% casein/kg diet), 30% protein (30P, 30% casein/kg diet), and 50% protein (50P, 50% casein/kg diet) diet groups and were subjected to azoxymethane-dextran sodium sulfate induced colon carcinogenesis...
August 2017: Nutrition Research and Practice
https://www.readbyqxmd.com/read/28748912/a-novel-allosteric-site-in-casein-kinase-2%C3%AE-discovered-using-combining-bioinformatics-and-biochemistry-methods
#17
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/28747709/trimethylamine-n-oxide-abolishes-the-chaperone-activity-of-%C3%AE-casein-an-intrinsically-disordered-protein
#18
Mohd Younus Bhat, Laishram Rajendrakumar Singh, Tanveer Ali Dar
Osmolytes (small molecules that help in circumventing stresses) are known to promote protein folding and prevent aggregation in the case of globular proteins. However, the effect of such osmolytes on the structure and function of intrinsically disordered proteins (IDPs) has not been clearly understood. Here we have investigated the effect of methylamine osmolytes on α-casein (an IDP present in mammalian milk) and discovered that TMAO (Trimethylamine-N-oxide) but not other methylamines renders α-casein functionless...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698370/g9a-coordinates-with-the-rpa-complex-to-promote-dna-damage-repair-and-cell-survival
#19
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/28655862/differential-abundance-of-ck1%C3%AE-provides-selectivity-for-pharmacological-ck1%C3%AE-activators-to-target-wnt-dependent-tumors
#20
Bin Li, Darren Orton, Leif R Neitzel, Luisana Astudillo, Chen Shen, Jun Long, Xi Chen, Kellye C Kirkbride, Thomas Doundoulakis, Marcy L Guerra, Julia Zaias, Dennis Liang Fei, Jezabel Rodriguez-Blanco, Curtis Thorne, Zhiqiang Wang, Ke Jin, Dao M Nguyen, Laurence R Sands, Floriano Marchetti, Maria T Abreu, Melanie H Cobb, Anthony J Capobianco, Ethan Lee, David J Robbins
Constitutive WNT activity drives the growth of various human tumors, including nearly all colorectal cancers (CRCs). Despite this prominence in cancer, no WNT inhibitor is currently approved for use in the clinic largely due to the small number of druggable signaling components in the WNT pathway and the substantial toxicity to normal gastrointestinal tissue. We have shown that pyrvinium, which activates casein kinase 1α (CK1α), is a potent inhibitor of WNT signaling. However, its poor bioavailability limited the ability to test this first-in-class WNT inhibitor in vivo...
June 27, 2017: Science Signaling
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