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https://www.readbyqxmd.com/read/29307372/biphasic-regulation-of-spindle-assembly-checkpoint-by-low-and-high-concentrations-of-resveratrol-leads-to-the-opposite-effect-on-chromosomal-instability
#1
Xihan Guo, Juan Ni, Xueqin Dai, Tao Zhou, Guofang Yang, Jinglun Xue, Xu Wang
Resveratrol (RSV) is a naturally occurring polyphenolic phytoalexin possessing numerous health-promoting effects. Chromosomal instability (CIN), usually results from defective spindle assembly checkpoint (SAC), is a major contributor to many diseases. While it's recently recognized that RSV exhibits a nonlinear dose response for disease prevention, whether it's the case for its role in CIN remains unknown. Here, we investigated the potential of a broad range of RSV concentrations (0.01-100μM) on CIN and the underlying mechanisms in human normal colon epithelial NCM460 cells...
January 2018: Mutation Research
https://www.readbyqxmd.com/read/29296234/the-pyrazolyl-urea-gege3-inhibits-tumor-angiogenesis-and-reveals-dystrophia-myotonica-protein-kinase-dmpk-1-as-a-novel-angiogenesis-target
#2
Elda Meta, Beat A Imhof, Patricia Ropraz, Richard J Fish, Chiara Brullo, Olga Bruno, Adama Sidibé
The limitation of targeting VEGF/VEGFR2 signalling to stop angiogenesis in cancer therapy has been blamed on re-activation of alternative receptor tyrosine kinases by compensatory angiogenic factors. Targeting MAPK and PI3K signaling pathways in endothelial cells may be an alternative or complementary approach. Herein we aimed to evaluate the antitumor and antiangiogenic potential of a novel pyrazolyl-urea kinase inhibitor, GeGe3, and to identify its kinase targets. We found GeGe3 to inhibit the proliferation of HUVEC and endothelial tube formation...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29282854/thermo-triggered-release-of-crispr-cas9-system-by-lipid-encapsulated-gold-nanoparticles-for-tumor-therapy
#3
Peng Wang, Lingmin Zhang, Wenfu Zheng, Liman Cong, Zhaorong Guo, Yangzhouyun Xie, Le Wang, Rongbing Tang, Qiang Feng, Yoh Hamada, Kohsuke Gonda, Zhijian Hu, Xiaochun Wu, Xingyu Jiang
CRISPR/Cas9 system is a powerful toolbox for gene editing. However, the low delivery efficiency is still a big hurdle influencing its applications. Herein, we report a strategy to deliver Cas9-sgPlk-1 plasmids (CP) by a multifunctional vehicle for tumor therapy. We condensed CP on TAT peptide-modified Au nanoparticles (AuNPs/CP, ACP) via electrostatic interactions, and coated lipids (DOTAP, DOPE, Cholesterol, PEG2000-DSPE) on the ACP to form lipid-encapsulated, AuNPs-condensed CP (LACP). LACP can enter tumor cells and release the CP into the cytosol by laser-triggered thermo-effects of the AuNPs and the CP can enter nuclei by TAT guidance, enabling effective knock-outs of target gene (Plk-1) of tumor (melanoma) and inhibition of the tumor both in vitro and in vivo...
December 28, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29276126/polo-like-kinase-couples-cytoplasmic-protein-gradients-in-the-c-%C3%A2-elegans-zygote
#4
Bingjie Han, Katianna R Antkowiak, Xintao Fan, Mallory Rutigliano, Sean P Ryder, Erik E Griffin
Intracellular protein gradients underlie essential cellular and developmental processes, but the mechanisms by which they are established are incompletely understood. During the asymmetric division of the C. elegans zygote, the RNA-binding protein MEX-5 forms an anterior-rich cytoplasmic gradient that causes the RNA-binding protein POS-1 to form an opposing, posterior-rich gradient. We demonstrate that the polo-like kinase PLK-1 mediates the repulsive coupling between MEX-5 and POS-1 by increasing the mobility of POS-1 in the anterior...
December 19, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29222184/phosphorylation-of-the-synaptonemal-complex-protein-syp-1-promotes-meiotic-chromosome-segregation
#5
Aya Sato-Carlton, Chihiro Nakamura-Tabuchi, Stephane Kazuki Chartrand, Tomoki Uchino, Peter Mark Carlton
Chromosomes that have undergone crossing over in meiotic prophase must maintain sister chromatid cohesion somewhere along their length between the first and second meiotic divisions. Although many eukaryotes use the centromere as a site to maintain cohesion, the holocentric organism Caenorhabditis elegans instead creates two chromosome domains of unequal length termed the short arm and long arm, which become the first and second site of cohesion loss at meiosis I and II. The mechanisms that confer distinct functions to the short and long arm domains remain poorly understood...
December 8, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29171762/plk4-a-link-between-centriole-biogenesis-and-cancer
#6
Radhika Radha Maniswami, Seema Prashanth, Archana Venkataramana Karanth, Sindhu Koushik, Hemalatha Govindaraj, Ramesh Mullangi, Sriram Rajagopal, Sooriya Kumar Jegatheesan
Polo like kinase (PLK) is known to play a pivotal role in various cell cycle processes to perpetuate proper division and growth of the cells. Polo like kinase-4 (PLK4) is one such kinase that appears in low abundance and plays a well-characterized role in centriole duplication. PLK4 deregulation (i.e. both overexpression and depletion of PLK4), leads to altered mitotic fidelity and thereby triggers tumorigenesis. Hence, over the last few years PLK4 has emerged as a potential therapeutic target for the treatment of various advanced cancers...
November 24, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29139009/lfm-a13-a-potent-inhibitor-of-polo-like-kinase-inhibits-breast-carcinogenesis-by-suppressing-proliferation-activity-and-inducing-apoptosis-in-breast-tumors-of-mice
#7
Kazim Sahin, Mehmet Tuzcu, Mehmet Yabas, Cemal Orhan, Nurhan Sahin, Ibrahim H Ozercan
The goals of the present study were to define the anticancer activity of LFM-A13 (α-cyano-β-hydroxy-β-methyl-N-(2,5-dibromophenyl)-propenamide), a potent inhibitor of Polo-like kinase (PLK), in a mouse mammary cancer model induced by 7,12-dimethylbenz(a)anthracene (DMBA) in vivo and explore its anticancer mechanism(s). We also examined whether the inhibition of PLK by LFM-A13 would improve the efficiency of paclitaxel in breast cancer growth in vivo. To do this, female BALB/c mice received 1 mg of DMBA once a week for 6 weeks with oral gavage...
November 15, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29122991/maternal-embryonic-leucine-zipper-kinase-is-a-novel-target-for-proliferation-associated-high-risk-myeloma
#8
Arnold Bolomsky, Roy Heusschen, Karin Schlangen, Kathrin Stangelberger, Joséphine Muller, Wolfgang Schreiner, Niklas Zojer, Jo Caers, Heinz Ludwig
Treatment of high-risk patients is a major challenge in multiple myeloma. This is especially true for patients assigned to the gene-expression-profiling defined proliferation subgroup. Although recent efforts have identified some key players of proliferative myeloma, genetic interactions and players that can be targeted with clinically effective drugs have to be identified to overcome the poor prognosis of these patients. We therefore examined maternal embryonic leucine zipper kinase (MELK) for its implications in hyper-proliferative myeloma and analysed the activity of the MELK inhibitor OTSSP167 in vitro and in vivo...
November 9, 2017: Haematologica
https://www.readbyqxmd.com/read/29122685/molecular-and-enzoinformatics-perspectives-of-targeting-polo-like-kinase-1-in-cancer-therapy
#9
REVIEW
Shazi Shakil, Mohammad H Baig, Shams Tabrez, Syed M Danish Rizvi, Syed K Zaidi, Ghulam M Ashraf, Shakeel A Ansari, Aftab Aslam Parwaz Khan, Mohammad H Al-Qahtani, Adel M Abuzenadah, Adeel G Chaudhary
Cancer is a disease that has been the focus of scientific research and discovery and continues to remain so. Polo-like kinases (PLKs) are basically serine/threonine kinase enzymes that control cell cycle from yeast to humans. PLK-1 stands for 'Polo-like kinase-1'. It is the most investigated protein among PLKs. It is crucial for intracellular processes, hence a 'hot' anticancer drug-target. Accelerating innovations in Enzoinformatics and associated molecular visualization tools have made it possible to literally perform a 'molecular level walk' traversing through and observing the minutest contours of the active site of relevant enzymes...
November 6, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29108241/identification-of-volasertib-resistant-mechanism-and-evaluation-of-combination-effects-with-volasertib-and-other-agents-on-acute-myeloid-leukemia
#10
Yoshiya Adachi, Yuichi Ishikawa, Hitoshi Kiyoi
Volasertib, a selective PLK1 inhibitor, was effective for acute myeloid leukemia (AML) patients in clinical trials. However, its efficacy was limited in mono-therapy, and a higher incidence of fatal events was revealed in the combination with low-dose cytarabine. Thus, optimization of combination therapy with volasertib and other agents is necessary for its clinical development, and the predictive factors for response or resistance to volasertib remain largely unknown. In this study, we investigated the resistance mechanism in volasertib-resistant cell lines and the combination effects with other agents, such as azacitidine (AZA), on AML cells...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29065307/channel-nucleoporins-recruit-plk-1-to-nuclear-pore-complexes-to-direct-nuclear-envelope-breakdown-in-c-%C3%A2-elegans
#11
Lisa Martino, Stéphanie Morchoisne-Bolhy, Dhanya K Cheerambathur, Lucie Van Hove, Julien Dumont, Nicolas Joly, Arshad Desai, Valérie Doye, Lionel Pintard
In animal cells, nuclear envelope breakdown (NEBD) is required for proper chromosome segregation. Whereas mitotic kinases have been implicated in NEBD, how they coordinate their activity to trigger this event is unclear. Here, we show that both in human cells and Caenorhabditis elegans, the Polo-like kinase 1 (PLK-1) is recruited to the nuclear pore complexes, just prior to NEBD, through its Polo-box domain (PBD). We provide evidence that PLK-1 localization to the nuclear envelope (NE) is required for efficient NEBD...
October 23, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29046358/translationally-controlled-tumor-protein-is-required-for-the-fast-growth-of-toxoplasma-gondii-and-maintenance-of-its-intracellular-development
#12
Jun Zheng, Yaping Chen, Zhaoran Li, Shinuo Cao, Zhaoxia Zhang, Honglin Jia
Translationally controlled tumor protein (TCTP) is a highly conserved, multifunctional protein that has been implicated in a range of cell physiologic processes, especially cell growth and development. A TCTP-like gene has been identified in the Toxoplasma genome [Toxoplasma gondii TCTP (TgTCTP)], although its function remains unknown. The sequence analysis of TgTCTP indicated that it is a highly conserved protein in eukaryotes. We found that the expression level of TgTCTP in the virulent RH strain was significantly higher than that in the avirulent PLK strain...
October 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28881998/systematic-identification-of-feature-combinations-for-predicting-drug-response-with-bayesian-multi-view-multi-task-linear-regression
#13
Muhammad Ammad-Ud-Din, Suleiman A Khan, Krister Wennerberg, Tero Aittokallio
Motivation: A prime challenge in precision cancer medicine is to identify genomic and molecular features that are predictive of drug treatment responses in cancer cells. Although there are several computational models for accurate drug response prediction, these often lack the ability to infer which feature combinations are the most predictive, particularly for high-dimensional molecular datasets. As increasing amounts of diverse genome-wide data sources are becoming available, there is a need to build new computational models that can effectively combine these data sources and identify maximally predictive feature combinations...
July 15, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28858266/kinases-involved-in-both-autophagy-and-mitosis
#14
REVIEW
Zhiyuan Li, Xin Zhang
Both mitosis and autophagy are highly regulated dynamic cellular processes and involve various phosphorylation events catalysed by kinases, which play vital roles in almost all physiological and pathological conditions. Mitosis is a key event during the cell cycle, in which the cell divides into two daughter cells. Autophagy is a process in which the cell digests its own cellular contents. Although autophagy regulation has mainly been studied in asynchronous cells, increasing evidence indicates that autophagy is in fact tightly regulated in mitosis...
August 31, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28819179/identification-of-polo-like-kinases-as-potential-novel-drug-targets-for-influenza-a-virus
#15
Marie O Pohl, Jessica von Recum-Knepper, Ariel Rodriguez-Frandsen, Caroline Lanz, Emilio Yángüez, Stephen Soonthornvacharin, Thorsten Wolff, Sumit K Chanda, Silke Stertz
In recent years genome-wide RNAi screens have revealed hundreds of cellular factors required for influenza virus infections in human cells. The long-term goal is to establish some of them as drug targets for the development of the next generation of antivirals against influenza. We found that several members of the polo-like kinases (PLK), a family of serine/threonine kinases with well-known roles in cell cycle regulation, were identified as hits in four different RNAi screens and we therefore studied their potential as drug target for influenza...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28778089/identification-of-volasertib-resistant-mechanism-and-evaluation-of-combination-effects-with-volasertib-and-other-agents-on-acute-myeloid-leukemia
#16
Yoshiya Adachi, Yuichi Ishikawa, Hitoshi Kiyoi
Volasertib, a selective PLK1 inhibitor, was effective for acute myeloid leukemia (AML) patients in clinical trials. However, its efficacy was limited in mono-therapy, and a higher incidence of fatal events was revealed in the combination with low-dose cytarabine. Thus, optimization of combination therapy with volasertib and other agents is necessary for its clinical development, and the predictive factors for response or resistance to volasertib remain largely unknown. In this study, we investigated the resistance mechanism in volasertib-resistant cell lines and the combination effects with other agents, such as azacitidine (AZA), on AML cells...
July 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28652654/bcl-2-degradation-is-an-additional-pro-apoptotic-effect-of-polo-like-kinase-inhibition-in-cholangiocarcinoma-cells
#17
Svenja Sydor, Sami Jafoui, Lena Wingerter, Sandra Swoboda, Joachim C Mertens, Guido Gerken, Ali Canbay, Andreas Paul, Christian D Fingas
AIM: To examine the influence on apoptotic mechanisms following inhibition of polo-like kinases as therapeutically approach for cholangiocellular cancer treatment. METHODS: As most cholangiocarcinomas are chemotherapy-resistant due to mechanisms preventing tumor cell death, we investigated the effect of Cisplatin on cholangiocellular carcinoma (CCA) cell lines KMCH-1 and Mz-Ch-1. Polo-like kinases (PLK) are important regulators of the cell cycle and their inhibition is discussed as a potential therapy while PLK inhibition can regulate apoptotic mediators...
June 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28648742/polo-like-kinase-2-modulates-%C3%AE-synuclein-protein-levels-by-regulating-its-mrna-production
#18
Rikke H Kofoed, Jin Zheng, Nelson Ferreira, Søren Lykke-Andersen, Mauro Salvi, Cristine Betzer, Lasse Reimer, Torben Heick Jensen, Karina Fog, Poul H Jensen
Variations in the α-synuclein-encoding SNCA gene represent the greatest genetic risk factor for Parkinson's disease (PD), and duplications/triplications of SNCA cause autosomal dominant familial PD. These facts closely link brain levels of α-synuclein with the risk of PD, and make lowering α-synuclein levels a therapeutic strategy for the treatment of PD and related synucleinopathies. In this paper, we corroborate previous findings on the ability of overexpressed Polo-like kinase 2 (PLK-2) to decrease cellular α-synuclein, but demonstrate that the process is independent of PLK-2 phosphorylating S129 in α-synuclein because a similar reduction is achieved with the non-phosphorable S129A mutant α-synuclein...
October 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28626898/polo-like-kinase-1-immunoreactivity-is-associated-with-metastases-in-cutaneous-melanoma
#19
Maciej Kaczorowski, Tomasz Borowiec, Piotr Donizy, Konrad Pagacz, Wojciech Fendler, Artur Lipinski, Agnieszka Halon, Rafal Matkowski
BACKGROUND: Polo-like kinase-1 (PLK-1) is one of the key regulators of cell cycle progression. Increased expression of PLK-1 was observed in several tumor types. METHODS: We immunohistochemically assessed PLK-1 expression in neoplastic and stromal compartments of 96 cutaneous melanomas, and analyzed associations between PLK-1 expression and clinicopathological characteristics. RESULTS: PLK-1 expression in cancer cells was not associated with basic clinical (eg, age, gender and tumor location) or histopathological (eg, Breslow thickness, mitotic rate and ulceration) parameters...
June 19, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28591657/agc-kinases-mechanisms-of-regulation-%C3%A2-and-innovative-drug-development
#20
REVIEW
Alejandro E Leroux, Jörg O Schulze, Ricardo M Biondi
The group of AGC kinases consists of 63 evolutionarily related serine/threonine protein kinases comprising PDK1, PKB/Akt, SGK, PKC, PRK/PKN, MSK, RSK, S6K, PKA, PKG, DMPK, MRCK, ROCK, NDR, LATS, CRIK, MAST, GRK, Sgk494, and YANK, while two other families, Aurora and PLK, are the most closely related to the group. Eight of these families are physiologically activated downstream of growth factor signalling, while other AGC kinases are downstream effectors of a wide range of signals. The different AGC kinase families share aspects of their mechanisms of inhibition and activation...
June 4, 2017: Seminars in Cancer Biology
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