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Polo-like kinase

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https://www.readbyqxmd.com/read/27924005/sub1-contacts-the-rna-polymerase-ii-stalk-to-modulate-mrna-synthesis
#1
Miguel Garavís, Noelia González-Polo, Paula Allepuz-Fuster, Jaime Alegrio Louro, Carlos Fernández-Tornero, Olga Calvo
Biogenesis of messenger RNA is critically influenced by the phosphorylation state of the carboxy-terminal domain (CTD) in the largest RNA polymerase II (RNAPII) subunit. Several kinases and phosphatases are required to maintain proper CTD phosphorylation levels and, additionally, several other proteins modulate them, including Rpb4/7 and Sub1. The Rpb4/7 heterodimer, constituting the RNAPII stalk, promote phosphatase functions and Sub1 globally influences CTD phosphorylation, though its mechanism remains mostly unknown...
December 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27922680/identification-of-key-genes-induced-by-platelet-rich-plasma-in-human-dermal-papilla-cells-using-bioinformatics-methods
#2
Haiyan Shen, Hanxiao Cheng, Haihua Chen, Jufang Zhang
Dermal papilla cells (DPCs) are located at the base of hair follicles, and are known to induce hair follicle regeneration. Platelet-rich plasma (PRP) functions in hair follicle regeneration. To investigate the influence of PRP on DPCs, the present study analyzed RNA‑seq data of human hair dermal papilla cells (HHDPCs) that were treated or untreated by PRP. The data included in the RNA‑seq were from two normal and two treated HHDPC samples. Following identification by Cuffdiff software, differentially expressed genes (DEGs) underwent enrichment analyses, and protein-protein interaction networks were constructed using Cytoscape software...
December 6, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27911707/the-plk4-stil-sas-6-module-at-the-core-of-centriole-duplication
#3
REVIEW
Christian Arquint, Erich A Nigg
Centrioles are microtubule-based core components of centrosomes and cilia. They are duplicated exactly once during S-phase progression. Central to formation of each new (daughter) centriole is the formation of a nine-fold symmetrical cartwheel structure onto which microtubule triplets are deposited. In recent years, a module comprising the protein kinase polo-like kinase 4 (PLK4) and the two proteins STIL and SAS-6 have been shown to stay at the core of centriole duplication. Depletion of any one of these three proteins blocks centriole duplication and, conversely, overexpression causes centriole amplification...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27908889/microrna-146a-induces-lineage-negative-bone-marrow-cell-apoptosis-and-senescence-by-targeting-polo-like-kinase-2-expression
#4
Shanming Deng, Huilan Wang, Chunling Jia, Shoukang Zhu, Xianming Chu, Qi Ma, Jianqin Wei, Emily Chen, Wei Zhu, Conrad J Macon, Dushyantha T Jayaweera, Derek M Dykxhoorn, Chunming Dong
OBJECTIVE: Lineage-negative bone marrow cells (lin- BMCs) are enriched in endothelial progenitor cells and mediate vascular repair. Aging-associated senescence and apoptosis result in reduced number and functionality of lin- BMCs, impairing their prorepair capacity. The molecular mechanisms underlying lin- BMC senescence and apoptosis are poorly understood. MicroRNAs (miRNAs) regulate many important biological processes. The identification of miRNA-mRNA networks that modulate the health and functionality of lin- BMCs is a critical step in understanding the process of vascular repair...
December 1, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27906199/microduplication-of-the-arid1a-gene-causes-intellectual-disability-with-recognizable-syndromic-features
#5
Marie Bidart, Michèle El Atifi, Sarra Miladi, John Rendu, Véronique Satre, Pierre F Ray, Caroline Bosson, Françoise Devillard, Daphné Lehalle, Valérie Malan, Jeanne Amiel, Maria Antonietta Mencarelli, Margherita Baldassarri, Alessandra Renieri, Jill Clayton-Smith, Gaëlle Vieville, Julien Thevenon, Florence Amblard, François Berger, Pierre-Simon Jouk, Charles Coutton
PURPOSE: To determine whether duplication of the ARID1A gene is responsible for a new recognizable syndrome. METHODS: We describe four patients with a 1p36.11 microduplication involving ARID1A as identified by array-comparative genomic hybridization . We performed comparative transcriptomic analysis of patient-derived fibroblasts using RNA sequencing and evaluated the impact of ARID1A duplication on the cell cycle using fluorescence-activated cell sorting. Functional relationships between differentially expressed genes were investigated with ingenuity pathway analysis (IPA)...
December 1, 2016: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/27904765/volasertib-suppresses-the-growth-of-human-hepatocellular-carcinoma-in-vitro-and-in-vivo
#6
Di-Wei Zheng, You-Qiu Xue, Yong Li, Jin-Ming Di, Jian-Ge Qiu, Wen-Ji Zhang, Qi-Wei Jiang, Yang Yang, Yao Chen, Meng-Ning Wei, Jia-Rong Huang, Kun Wang, Xing Wei, Zhi Shi
Hepatocellular carcinoma (HCC) is the sixth most frequent malignant tumor with poor prognosis, and its clinical therapeutic outcome is poor. Volasertib, a potent small molecular inhibitor of polo-like kinase 1 (PLK1), is currently tested for treatment of multiple cancers in the clinical trials. However, the antitumor effect of volasertib on HCC is still unknown. In this study, our data show that volasertib is able to induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the spindle abnormalities in human HCC cells...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27902970/activity-of-the-novel-polo-like-kinase-4-inhibitor-cfi-400945-in-pancreatic-cancer-patient-derived-xenografts
#7
I Lohse, J M Mason, P J Cao, Melania Pintilie, M R Bray, D W Hedley
BACKGROUND: Polo-like kinase 4 (PKL4) plays a key role in centriole replication. Hence PLK4 inhibition disrupts mitosis, and offers a novel approach to treating chromosomally unstable cancers, including pancreatic cancer. CFI-400945 is a first in class small molecule PLK4 inhibitor, currently undergoing early phase clinical trials. RESULTS: Treatment with CFI-400945 significantly reduced tumor growth and increased survival in four out of the six models tested. Consistent with PLK4 inhibition, we observed reduced expression of the proliferation marker Ki-67 associated with an increase in nuclear diameter during treatment with CFI-400945...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902479/identification-of-a-novel-polo-like-kinase-1-inhibitor-that-specifically-blocks-the-functions-of-polo-box-domain
#8
Yunyu Chen, Jing Zhang, Dongsheng Li, Jiandong Jiang, Yanchang Wang, Shuyi Si
Polo-like kinase 1 (Plk1) is a promising target for cancer therapy due to its essential role in cell division. In addition to a highly conserved kinase domain, Plk1 also contains a Polo-Box domain (PBD), which is essential for Plk1's subcellular localization and mitotic functions. We adopted a fluorescence polarization assay and identified a new Plk1 PBD inhibitor T521 from a small-molecule compound library. T521 specifically inhibits the PBD of Plk1, but not those of Plk2-3. T521 exhibits covalent binding to some lysine residues of Plk1 PBD, which causes significant changes in the secondary structure of Plk1 PBD...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899378/cervical-cancer-growth-is-regulated-by-a-c-abl-plk1-signaling-axis
#9
Xu Yang, Gang Chen, Wei Li, Changmin Peng, Yue Zhu, Xiaoming Yang, Teng Li, Cheng Cao, Huadong Pei
The non-receptor tyrosine kinase c-ABL controls cell growth but its contributions in solid tumors are not fully understood. Here we report that the Polo-like kinase PLK1, an essential mitotic kinase regulator, is an important downstream effector of c-ABL in regulating the growth of cervical cancer. c-ABL interacted with and phosphorylated PLK1. Phosphorylation of PLK1 by c-ABL inhibited PLK1 ubiquitination and degradation and enhanced its activity, leading to cell cycle progression and tumor growth. Both c-ABL and PLK1 were overexpressed in cervical carcinoma...
November 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27888710/plk1-a-potential-target-for-cancer-therapy
#10
REVIEW
Zhixian Liu, Qingrong Sun, Xiaosheng Wang
Polo-like kinase 1 (PLK1) plays an important role in the initiation, maintenance, and completion of mitosis. Dysfunction of PLK1 may promote cancerous transformation and drive its progression. PLK1 overexpression has been found in a variety of human cancers and was associated with poor prognoses in cancers. Many studies have showed that inhibition of PLK1 could lead to death of cancer cells by interfering with multiple stages of mitosis. Thus, PLK1 is expected to be a potential target for cancer therapy. In this article, we examined PLK1's structural characteristics, its regulatory roles in cell mitosis, PLK1 expression, and its association with survival prognoses of cancer patients in a wide variety of cancer types, PLK1 interaction networks, and PLK1 inhibitors under investigation...
November 23, 2016: Translational Oncology
https://www.readbyqxmd.com/read/27882722/designed-inhibitor-for-nuclear-localization-signal-of-polo-like-kinase-1-induces-mitotic-arrest
#11
Fangjin Chen, Xiaolong Zhuo, Tan Qin, Xiao Guo, Chuanmao Zhang, Luhua Lai
Polo-like kinase 1 (Plk1), a member of polo-like kinase family, regulates multiple essential steps of the cell cycle progression. Plk1 is overexpressed in multiple cancer cell lines and considered to be a prime anticancer target. Plk1 accumulates in the nucleus during S and G2 phases by its bipartite nuclear localization signal (NLS) sequence, which is crucial for Plk1 regulation during normal cell cycle progression. Here, through combined computational and experimental studies, we identified compound D110, which inhibits Plk1 kinase activity with an IC50 of 85 nm and blocks the nuclear localization of Plk1 during S and G2 phases...
November 24, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27878946/targeted-inhibition-of-polo-like-kinase-1-by-a-novel-small-molecule-inhibitor-induces-mitotic-catastrophe-and-apoptosis-in-human-bladder-cancer-cells
#12
Zhe Zhang, Guojun Zhang, Chuize Kong
Bladder cancer is a common cancer with particularly high recurrence after transurethral resection. Despite improvements in neoadjuvant chemotherapy, the outcome of patients with advanced bladder cancer has changed very little. In this study, the anti-tumour activities of a novel Polo-like kinase 1 (PLK1) inhibitor (RO3280) was evaluated in vitro and in vivo in the bladder carcinoma cell lines 5637 and T24. MTT assays, colony-formation assays, flow cytometry, cell morphological analysis and trypan blue exclusion assays were used to examine the proliferation, cell cycle distribution and apoptosis of bladder carcinoma cells with or without RO3280 treatment...
November 23, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27875595/phosphorylation-of-serine-235-of-the-hepatitis-c-virus-non-structural-protein-ns5a-by-multiple-kinases
#13
Kuan-Ying Lee, Yi-Hung Chen, Shih-Chin Hsu, Ming-Jiun Yu
Phosphorylation at serine 235 (S235) of the hepatitis C virus (HCV) non-structural protein 5A (NS5A) plays a critical role in the viral life cycle. For medical and virological interests, we exploited the HEK293T kidney cells to test 3 candidate protein kinases on NS5A S235 phosphorylation. Inhibitors that inhibit casein kinase I α (CKIα), polo-like kinase I (PlKI) or calmodulin-dependent kinase II (CaMKII) all reduced NS5A S235 phosphorylation. CKIα was studied previously and PlKI had severe cytotoxicity, thus CaMKII was selected for validation in the Huh7...
2016: PloS One
https://www.readbyqxmd.com/read/27874094/identification-of-polo-like-kinase-1-interaction-inhibitors-using-a-novel-cell-based-assay
#14
Karine Normandin, Jean-François Lavallée, Marie Futter, Alexandre Beautrait, Jean Duchaine, Sébastien Guiral, Anne Marinier, Vincent Archambault
Polo-like kinase 1 (Plk1) plays several roles in cell division and it is a recognized cancer drug target. Plk1 levels are elevated in cancer and several types of cancer cells are hypersensitive to Plk1 inhibition. Small molecule inhibitors of the kinase domain (KD) of Plk1 have been developed. Their selectivity is limited, which likely contributes to their toxicity. Polo-like kinases are characterized by a Polo-Box Domain (PBD), which mediates interactions with phosphorylation substrates or regulators. Inhibition of the PBD could allow better selectivity or result in different effects than inhibition of the KD...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27863657/development-and-characterization-of-polo-like-kinase-2-loaded-nanoparticles-a-novel-strategy-for-serine-129-phosphorylation-of-alpha-synuclein
#15
C Rodríguez-Nogales, E Garbayo, I Martínez-Valbuena, V Sebastián, M R Luquin, M J Blanco-Prieto
Polo like kinase 2 (PLK2), a serine/threonine serum inducible kinase, has been proposed to be the major factor responsible for phosphorylating alpha-synuclein (α-syn) at Serine-129 (Ser-129) in Parkinson's disease (PD). A suitable strategy to gain insights into PLK2's biological effects might be to increase PLK2 intracellular levels with the aim of reproducing the slow progressive neuronal changes that occur in PD. The goal of this study was to develop and characterize a novel drug delivery system (DDS) for PLK2 cytosolic delivery using Total recirculating one machine system (TROMS), a technique capable of encapsulating fragile molecules while maintaining their native properties...
November 30, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27861885/sensitivity-of-tp53-mutated-cancer-cells-to-the-phytoestrogen-genistein-is-associated-with-direct-inhibition-of-plk1-activity
#16
Sol-Bi Shin, Sang-Uk Woo, Young Won Chin, Young-Joo Jang, Hyungshin Yim
Polo-like kinase 1 (Plk1), a conserved Ser/Thr mitotic kinase, has been identified as a promising target for anticancer drug development because its overexpression is correlated with malignancy. Here, we found that genistein, an isoflavone, inhibits Plk1 kinase activity directly. Previously the mitotic disturbance phenomenon induced by treatment with genistein was not fully explained by its inhibitory effect on EGFR. In kinase profiling assays, it showed selectivity relative to a panel of kinases, including EGFR...
November 9, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27857970/bora-dependent-plk1-regulation-a-new-weapon-for-cancer-therapy
#17
Luca Cirillo, Yann Thomas, Lionel Pintard, Monica Gotta
The mitotic kinase polo like kinase 1 (PLK1) is overexpressed in many cancers and its inhibition slows down proliferation and increases apoptosis in cancer cell lines. Understanding how PLK1 is activated is therefore crucial for the development of novel PLK1 inhibitors with anticancer properties. We recently identified a conserved regulatory loop leading to PLK1 activation that involves cyclin-dependent kinase 1 (CDK1).
2016: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/27831827/mitotic-entry-the-interplay-between-cdk1-plk1-and-bora
#18
Alfonso Parrilla, Luca Cirillo, Yann Thomas, Monica Gotta, Lionel Pintard, Anna Santamaria
Polo-like kinase 1 (Plk1) is an important mitotic kinase that is crucial for entry into mitosis after recovery from DNA damage-induced cell cycle arrest. Plk1 activation is promoted by the conserved protein Bora (SPAT-1 in C. elegans), which stimulates the phosphorylation of a conserved residue in the activation loop by the Aurora A kinase. In a recent article published in Cell Reports, we show that the master mitotic kinase Cdk1 contributes to Plk1 activation through SPAT-1/Bora phosphorylation. We identified 3 conserved Sp/Tp residues that are located in the N-terminal, most conserved part, of SPAT-1/Bora...
November 10, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27830001/plk1-promotes-epithelial-mesenchymal-transition-and-metastasis-of-gastric-carcinoma-cells
#19
Xiao Peng Cai, Liang Dong Chen, Hai Bin Song, Chun Xiao Zhang, Ze Wei Yuan, Zhen Xian Xiang
Cancer cell epithelial-mesenchymal transition (EMT) is the crucial event for cancer progression and plays a vital role in the metastasis of cancer cells. Activation of Polo-like kinase 1 (PLK1) signaling has been implicated as the critical event in several tumor metastasis and EMT, however, whether PLK1 participates in gastric carcinoma metastasis and EMT still remains unclear. For this study, we elucidated the potential physiological function of PLK1 in the metastasis of gastric tumors, as well its distinct role in cells EMT and subsequently determined the mechanism involved in PLK1 regulated...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27822032/co-delivery-of-doxorubicin-and-recombinant-plasmid-phsp70-plk1-shrna-by-bacterial-magnetosomes-for-osteosarcoma-therapy
#20
Li Cheng, Youqun Ke, Shuisheng Yu, Juehua Jing
To explore a novel combination of chemotherapy, gene therapy, and thermotherapy for osteosarcoma, a targeted heat-sensitive co-delivery system based on bacterial magnetosomes (BMs) was developed. The optimal culture conditions of magnetotactic bacteria (MTB) AMB-1 and characterization of BMs were achieved. A recombinant eukaryotic plasmid heat shock protein 70-polo-like kinase 1-short hairpin RNA (pHSP70-Plk1-shRNA) under transcriptional control of a thermosensitive promoter (human HSP70 promoter) was constructed for gene therapy...
2016: International Journal of Nanomedicine
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