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Polo-like kinase

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https://www.readbyqxmd.com/read/29228663/targeting-plk1-as-a-novel-chemopreventive-approach-to-eradicate-preneoplastic-mucosal-changes-in-the-head-and-neck
#1
D Vicky de Boer, Sanne R Martens-de Kemp, Marijke Buijze, Marijke Stigter-van Walsum, Elisabeth Bloemena, Ralf Dietrich, C René Leemans, Victor W van Beusechem, Boudewijn J M Braakhuis, Ruud H Brakenhoff
Head and neck squamous cell carcinomas (HNSCC) and local relapses thereof develop in preneoplastic fields in the mucosal linings of the upper aerodigestive tract. These fields are characterized by tumor-associated genetic changes, are frequently dysplastic and occasionally macroscopically visible. Currently, no adequate treatment options exist to prevent tumor development. Array-based screening with a panel of tumor-lethal small interfering RNAs (siRNAs) identified Polo-like kinase 1 (PLK1) as essential for survival of preneoplastic cells...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228610/targeting-polo-like-kinase-1-in-smarcb1-deleted-atypical-teratoid-rhabdoid-tumor
#2
Irina Alimova, Angela M Pierce, Peter Harris, Andrew Donson, Diane K Birks, Eric Prince, Ilango Balakrishnan, Nicholas K Foreman, Marcel Kool, Lindsey Hoffman, Sujatha Venkataraman, Rajeev Vibhakar
Atypical teratoid rhabdoid tumor (ATRT) is an aggressive and malignant pediatric brain tumor. Polo-like kinase 1 (PLK1) is highly expressed in many cancers and essential for mitosis. Overexpression of PLK1 promotes chromosome instability and aneuploidy by overriding the G2-M DNA damage and spindle checkpoints. Recent studies suggest that targeting PLK1 by small molecule inhibitors is a promising approach to tumor therapy. We investigated the effect of PLK1 inhibition in ATRT. Gene expression analysis showed that PLK1 was overexpressed in ATRT patient samples and tumor cell lines...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220793/design-synthesis-and-biological-evaluation-of-novel-highly-selective-polo-like-kinase-2-inhibitors-based-on-the-tetrahydropteridin-chemical-scaffold
#3
Mei-Miao Zhan, Yang Yang, Jinfeng Luo, Xing-Xing Zhang, Xuan Xiao, Shiyu Li, Kai Cheng, Zhouling Xie, Zhengchao Tu, Chenzhong Liao
Polo-like kinase 2 (Plk2) is a potential target for the treatment of cancer, which displays an important role in tumor cell proliferation and survival. In this report, according to the analysis of critical amino acid residue differences among Plk1, Plk2 and Plk3, and structure-based drug design strategies, two novel series of selective Plk2 inhibitors based on tetrahydropteridin chemical scaffold were designed and synthesized to target two specific residues, Lys86 and Tyr161 of Plk2. All compounds were evaluated for their inhibitory activity against Plk1-Plk3 and the cellular inhibition activity on six different human cancer cell lines...
November 23, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29209646/re-investigating-plk1-inhibitors-as-antimitotic-agents
#4
Quentin Delacour, Olivier Gavet
Polo-like kinase 1 (PLK1) plays key roles during mitosis, prompting the development of PLK1 inhibitors for anticancer therapy. We recently determined that PLK1 is crucially required for entry into mitosis. Hence, we discuss the potential and limitations of PLK1 inhibition strategies to promote mitotic arrest and death of cancer cells.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/29201613/genome-editing-for-cancer-therapy-delivery-of-cas9-protein-sgrna-plasmid-via-a-gold-nanocluster-lipid-core-shell-nanocarrier
#5
Peng Wang, Lingmin Zhang, Yangzhouyun Xie, Nuoxin Wang, Rongbing Tang, Wenfu Zheng, Xingyu Jiang
The type II bacterial clustered, regularly interspaced, short palindromic repeats (CRISPR)-Cas9 (CRISPR-associated protein) system (CRISPR-Cas9) is a powerful toolbox for gene-editing, however, the nonviral delivery of CRISPR-Cas9 to cells or tissues remains a key challenge. This paper reports a strategy to deliver Cas9 protein and single guide RNA (sgRNA) plasmid by a nanocarrier with a core of gold nanoclusters (GNs) and a shell of lipids. By modifying the GNs with HIV-1-transactivator of transcription peptide, the cargo (Cas9/sgRNA) can be delivered into cell nuclei...
November 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://www.readbyqxmd.com/read/29196561/hierarchical-regulation-of-centromeric-cohesion-protection-by-meikin-and-shugoshin-during-meiosis-i
#6
Seira Miyazaki, Jihye Kim, Takeshi Sakuno, Yoshinori Watanabe
The kinetochore is the key apparatus regulating chromosome segregation. Particularly in meiosis, unlike in mitosis, sister kinetochores are captured by microtubules emanating from the same spindle pole (mono-orientation), and sister chromatid cohesion mediated by cohesin is protected at centromeres in the following anaphase. Shugoshin, which localizes to centromeres depending on the phosphorylation of histone H2A by Bub1 kinase, plays a central role in protecting meiotic cohesin Rec8 from separase cleavage...
December 1, 2017: Cold Spring Harbor Symposia on Quantitative 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
#7
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/29190933/the-anticipating-value-of-plk1-for-diagnosis-progress-and-prognosis-and-its-prospective-mechanism-in-gastric-cancer-a-comprehensive-investigation-based-on-high-throughput-data-and-immunohistochemical-validation
#8
Peng Lin, Dan-Dan Xiong, Yi-Wu Dang, Hong Yang, Yun He, Dong-Yue Wen, Xin-Gan Qin, Gang Chen
Polo-like kinase 1 (PLK1) is a multi-functional protein and its aberrant expression is a driver of cancerous transformation and progression. To increase our understanding of the clinical value and potential molecular mechanism of PLK1 in gastric cancer (GC), we performed this comprehensive investigation. A total of 25 datasets and 12 publications were finally incorporated. Additional immunohistochemistry was conducted to validate the expression pattern of PLK1 in GC. The pooled standard mean deviation (SMD) indicated that PLK1 mRNA was up-regulated in GC (SMD=1...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29187890/decreased-kpnb1-expression-is-induced-by-plk1-inhibition-and-leads-to-apoptosis-in-lung-adenocarcinoma
#9
Noboru Sekimoto, Yutaka Suzuki, Sumio Sugano
Lung cancer is a major cause of death worldwide, with lung adenocarcinoma being the most frequently diagnosed subtype in Japan. Finding the target of an anticancer drug can improve lung adenocarcinoma treatments. Polo-like kinase 1 (PLK1) is an essential mitotic kinase in mitotic progression, and PLK1 inhibition induces cell cycle arrest and apoptosis in tumor cells. In addition, a variety of PLK1 inhibitors have been identified for cancer treatments. In this study, we looked for the target gene of the anticancer drug that has synergy with PLK1 inhibitors...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29186071/volasertib-enhances-sensitivity-to-trail-in-renal-carcinoma-caki-cells-through-downregulation-of-c-flip-expression
#10
Mi-Yeon Jeon, Kyoung-Jin Min, Seon Min Woo, Seung Un Seo, Shin Kim, Jong-Wook Park, Taeg Kyu Kwon
Polo-like kinase 1 (PLK1) plays major roles in cell cycle control and DNA damage response. Therefore, PLK1 has been investigated as a target for cancer therapy. Volasertib is the second-in class dihydropteridinone derivate that is a specific PLK1 inhibitor. In this study, we examined that combining PLK1 inhibitor with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) would have an additive and synergistic effect on induction of apoptosis in cancer cells. We found that volasertib alone and TRAIL alone had no effect on apoptosis, but the combined treatment of volasertib and TRAIL markedly induced apoptosis in Caki (renal carcinoma), A498 (renal carcinoma) and A549 (lung carcinoma) cells, but not in normal cells (human skin fibroblast cells and mesangial cells)...
November 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29178204/tbsmee1-regulates-hook-complex-morphology-and-the-rate-of-flagellar-pocket-uptake-in-trypanosoma-brucei
#11
Jenna A Perry, Amy N Sinclair-Davis, Michael R McAllaster, Christopher L de Graffenried
Trypanosoma brucei employs multiple mechanisms to evade detection by its insect and mammalian hosts. The flagellar pocket (FP) is the exclusive site of uptake from the environment in trypanosomes and shields receptors from exposure to the host. The FP neck is tightly associated with the flagellum via a series of cytoskeletal structures that include the hook complex (HC) and the centrin arm. These structures are implicated in facilitating macromolecule entry into the FP and nucleating the flagellum attachment zone (FAZ), which adheres the flagellum to the cell surface...
November 27, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/29171762/plk4-a-link-between-centriole-biogenesis-and-cancer
#12
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/29170437/the-responses-of-cancer-cells-to-plk1-inhibitors-reveal-a-novel-protective-role-for-p53-in-maintaining-centrosome-separation
#13
Linda Smith, Raed Farzan, Simak Ali, Laki Buluwela, Adrian Saurin, David W Meek
Polo-like kinase-1 (PLK1) plays a major role in driving mitotic events, including centrosome disjunction and separation, and is frequently over-expressed in human cancers. PLK1 inhibition is a promising therapeutic strategy and works by arresting cells in mitosis due to monopolar spindles. The p53 tumour suppressor protein is a short-lived transcription factor that can inhibit the growth, or stimulate the death, of developing cancer cells. Curiously, although p53 normally acts in an anti-cancer capacity, it can offer significant protection against inhibitors of PLK1, but the events underpinning this effect are not known...
November 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29166821/the-ribosomal-dna-metaphase-loop-of-saccharomyces-cerevisiae-gets-condensed-upon-heat-stress-in-a-cdc14-independent-torc1-dependent-manner
#14
Emiliano Matos-Perdomo, Félix Machín
Chromosome morphology in Saccharomyces cerevisiae is only visible at the microscopic level in the ribosomal DNA array (rDNA). The rDNA has been thus used as a model to characterize condensation and segregation of sister chromatids in mitosis. It has been established that the metaphase structure ("loop") depends, among others, on the condensin complex; whereas its segregation also depends on that complex, the Polo-like kinase Cdc5 and the cell cycle master phosphatase Cdc14. In addition, Cdc14 also drives rDNA hypercondensation in telophase...
November 23, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29166606/sumoylation-promotes-nuclear-import-and-stabilization-of-polo-like-kinase-1-to-support-its-mitotic-function
#15
Donghua Wen, Jianguo Wu, Lei Wang, Zheng Fu
As a pivotal mitotic regulator, polo-like kinase 1 (PLK1) is under highly coordinated and multi-layered regulation. However, the pathways that control PLK1's activity and function have just begun to be elucidated. PLK1 has recently been shown to be functionally modulated by post-translational modifications (PTMs), including phosphorylation and ubiquitination. Herein, we report that SUMOylation plays an essential role in regulating PLK1's mitotic function. We found that Ubc9 was recruited to PLK1 upon initial phosphorylation and activation by CDK1/cyclin B...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29163849/the-therapeutic-potential-of-cell-cycle-targeting-in-multiple-myeloma
#16
REVIEW
Anke Maes, Eline Menu, Kim De Veirman, Ken Maes, Karin Vand Erkerken, Elke De Bruyne
Proper cell cycle progression through the interphase and mitosis is regulated by coordinated activation of important cell cycle proteins (including cyclin-dependent kinases and mitotic kinases) and several checkpoint pathways. Aberrant activity of these cell cycle proteins and checkpoint pathways results in deregulation of cell cycle progression, which is one of the key hallmarks of cancer. Consequently, intensive research on targeting these cell cycle regulatory proteins identified several candidate small molecule inhibitors that are able to induce cell cycle arrest and even apoptosis in cancer cells...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29158823/engineered-zn-ii-dipicolylamine-gold-nanorod-provides-effective-prostate-cancer-treatment-by-combining-sirna-delivery-and-photothermal-therapy
#17
Kyung Hyun Min, Young-Hwa Kim, Zhantong Wang, Jihoon Kim, Jee Seon Kim, Sun Hwa Kim, Kwangmeyung Kim, Ick Chan Kwon, Dale O Kiesewetter, Xiaoyuan Chen
Combination cancer treatment has emerged as a critical approach to achieve remarkable anticancer effect. In this study, we prepared a theranostic nanoformulation that allows for photoacoustic imaging as well as combination gene and photothermal therapy. Gold nanorods (GNR) were coated with dipicolyl amine (DPA), which forms stable complexes with Zn(2+) cations. The resulting nanoparticles, Zn(II)/DPA-GNR, recognize phosphate-containing molecules, including siRNA, because of the specific interaction between Zn(II) and the phosphates...
2017: Theranostics
https://www.readbyqxmd.com/read/29143380/polo-like-kinase-1-inhibition-results-in-misaligned-chromosomes-and-aberrant-spindles-in-porcine-oocytes-during-the-first-meiotic-division
#18
Y Liao, D Lin, P Cui, B Abbasi, C Chen, Z Zhang, Y Zhang, Y Dong, R Rui, S Ju
Polo-like kinase 1 (Plk1), a type of serine/threonine protein kinase, has been implicated in various functions in the regulation of mitotic processes. However, these kinase's roles in meiotic division are not fully understood, particularly in the meiotic maturation of porcine oocytes. In this study, the expression and spatiotemporal localization of Plk1 were initially assessed in the meiotic process of pig oocytes by utilizing Western blotting with immunofluorescent staining combined with confocal microscopy imaging technique...
November 16, 2017: Reproduction in Domestic Animals, Zuchthygiene
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
#19
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/29138491/sumoylation-regulates-the-localization-and-activity-of-polo-like-kinase-1-during-cell-cycle-in-the-silkworm-bombyx-mori
#20
Zhiqing Li, Qixin Cui, Jian Xu, Daojun Cheng, Xiaoyan Wang, Bingqian Li, Jae Man Lee, Qingyou Xia, Takahiro Kusakabe, Ping Zhao
Polo-like kinase 1 (Plk1) is a crucial cell cycle regulator by its specific localization and activity during cell cycle. It has been shown that the phosphorylation and ubiquitylation of Plk1 are required for its own activation and localization. Here, we report that SUMOylation regulates the activity of Plk1 in the lepidopteran insect of Bombyx mori. In the absence of SUMOylation, it causes the lost localization of Plk1 on centrosomes and kinetochores, as well as an uneven distribution in midzone. We further identify that the putative SUMOylation site of Bombyx Plk1 at lysine 466 is required for its localization on centrosomes, and K466 mutation in Plk1 could influence its interaction with Smt3/Ubc9 complex...
November 14, 2017: Scientific Reports
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