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https://www.readbyqxmd.com/read/28074435/plk1-inhibition-leads-to-a-failure-of-mitotic-division-during-the-first-mitotic-division-in-pig-embryos
#1
Zixiao Zhang, Changchao Chen, Panpan Cui, Yaya Liao, Lingyun Yao, Yue Zhang, Rong Rui, Shiqiang Ju
PURPOSE: This study was conducted to examine the dynamic distribution of polo-like 1 kinase (Plk1) and the possible role it plays in first mitotic division during early porcine embryo development. METHODS: Indirect immunofluorescence and confocal microscopy imaging techniques combined with western blot analyses were used to study the dynamic expression and subcellular localization of Plk1 protein in pig parthenogenetic embryos. Finally, a selective Plk1 inhibitor, GSK461364, was used to evaluate the potential role of Plk1 during this special stage...
January 10, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28069876/targeting-plk1-to-enhance-efficacy-of-olaparib-in-castration-resistant-prostate-cancer
#2
Xiaoqi Liu, Jie Li, Ruixin Wang, Yifan Kong, Meaghan M Broman, Colin Carlock, Long Chen, Zhiguo Li, Elia Farah, Timothy L Ratliff
Olaparib is a FDA-approved PARP inhibitor (PARPi) that has shown promise as a synthetic lethal treatment approach for BRCA-mutant castration-resistant prostate cancer (CRPC) in clinical use. However, emerging data has also shown that even BRCA-mutant cells may be resistant to PARPi. The mechanistic basis for these drug resistances is poorly understood. Polo-like kinase 1 (Plk1), a critical regulator of many cell cycle events, is significantly elevated upon castration of mice carrying xenograft prostate tumors...
January 9, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28069132/molecular-regulation-of-the-spindle-assembly-checkpoint-by-kinases-and-phosphatases
#3
G Manic, F Corradi, A Sistigu, S Siteni, I Vitale
The spindle assembly checkpoint (SAC) is a surveillance mechanism contributing to the preservation of genomic stability by monitoring the microtubule attachment to, and/or the tension status of, each kinetochore during mitosis. The SAC halts metaphase to anaphase transition in the presence of unattached and/or untensed kinetochore(s) by releasing the mitotic checkpoint complex (MCC) from these improperly-oriented kinetochores to inhibit the anaphase-promoting complex/cyclosome (APC/C). The reversible phosphorylation of a variety of substrates at the kinetochore by antagonistic kinases and phosphatases is one major signaling mechanism for promptly turning on or turning off the SAC...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28066849/gold-nanorod-embedded-large-pore-mesoporous-organosilica-nanospheres-for-gene-and-photothermal-cooperative-therapy-of-triple-negative-breast-cancer
#4
Qianqian Ni, Zhaogang Teng, Meng Dang, Ying Tian, Yunlei Zhang, Peng Huang, Xiaodan Su, Nan Lu, Zhenlu Yang, Wei Tian, Shouju Wang, Wenfei Liu, Yuxia Tang, Guangming Lu, Longjiang Zhang
To date, clinicians still lack an effective strategy to treat triple negative breast cancer (TNBC). In this work, we design for the first time a gold nanorod embedded large-pore mesoporous organosilica (GNR@LPMO) nanoplatform for gene and photothermal cooperative therapy of TNBC. The synthesized GNR@LPMOs possess a uniform size (175 nm), high surface area (631 m(2) g(-1)), large pore size, excellent photothermal efficiency, and good biocompatibility. Thanks to the large-pore mesoporous organosilica layer, the GNR@LPMO nanoplatforms display much higher loading capacity of siRNA compared with traditional liposome and bare gold nanorods...
January 9, 2017: Nanoscale
https://www.readbyqxmd.com/read/28043128/formulation-and-evaluation-of-anisamide-targeted-amphiphilic-cyclodextrin-nanoparticles-to-promote-therapeutic-gene-silencing-in-a-3d-prostate-cancer-bone-metastases-model
#5
James C Evans, Meenakshi Malhotra, Kathleen A Fitzgerald, Jianfeng Guo, Michael F Cronin, Caroline M Curtin, Fergal J O'Brien, Raphael Darcy, Caitriona M O'Driscoll
In recent years, RNA interference (RNAi) has emerged as a potential therapeutic offering the opportunity to treat a wide range of diseases, including prostate cancer. Modified cyclodextrins have emerged as effective gene delivery vectors in a range of disease models. The main objective of the current study was to formulate anisamide-targeted cyclodextrin nanoparticles to interact with the sigma receptor (overexpressed on the surface of prostate cancer cells). The inclusion of octaarginine in the nanoparticle optimized uptake and endosomal release of siRNA in two different prostate cancer cell lines (PC3 and DU145 cells)...
January 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28036269/the-gsk461364-plk1-inhibitor-exhibits-strong-antitumoral-activity-in-preclinical-neuroblastoma-models
#6
Kristian W Pajtler, Natalie Sadowski, Sandra Ackermann, Kristina Althoff, Kerstin Schönbeck, Katharina Batzke, Simon Schäfers, Andrea Odersky, Lukas Heukamp, Kathy Astrahantseff, Annette Künkele, Hedwig E Deubzer, Alexander Schramm, Annika Sprüssel, Theresa Thor, Sven Lindner, Angelika Eggert, Matthias Fischer, Johannes H Schulte
Polo-like kinase 1 (PLK1) is a serine/threonine kinase that promotes G2/M-phase transition, is expressed in elevated levels in high-risk neuroblastomas and correlates with unfavorable patient outcome. Recently, we and others have presented PLK1 as a potential drug target for neuroblastoma, and reported that the BI2536 PLK1 inhibitor showed antitumoral actvity in preclinical neuroblastoma models. Here we analyzed the effects of GSK461364, a competitive inhibitor for ATP binding to PLK1, on typical tumorigenic properties of preclinical in vitro and in vivo neuroblastoma models...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28024153/hiv-1-blocks-the-signaling-adaptor-mavs-to-evade-antiviral-host-defense-after-sensing-of-abortive-hiv-1-rna-by-the-host-helicase-ddx3
#7
Sonja I Gringhuis, Nina Hertoghs, Tanja M Kaptein, Esther M Zijlstra-Willems, Ramin Sarrami-Fooroshani, Joris K Sprokholt, Nienke H van Teijlingen, Neeltje A Kootstra, Thijs Booiman, Karel A van Dort, Carla M S Ribeiro, Agata Drewniak, Teunis B H Geijtenbeek
The mechanisms by which human immunodeficiency virus 1 (HIV-1) avoids immune surveillance by dendritic cells (DCs), and thereby prevents protective adaptive immune responses, remain poorly understood. Here we showed that HIV-1 actively arrested antiviral immune responses by DCs, which contributed to efficient HIV-1 replication in infected individuals. We identified the RNA helicase DDX3 as an HIV-1 sensor that bound abortive HIV-1 RNA after HIV-1 infection and induced DC maturation and type I interferon responses via the signaling adaptor MAVS...
December 26, 2016: Nature Immunology
https://www.readbyqxmd.com/read/28008150/prkar2b-plays-an-oncogenic-role-in-the-castration-resistant-prostate-cancer
#8
Jianjun Sha, Wei Xue, Baijun Dong, Jiahua Pan, Xiaorong Wu, Dong Li, Dongming Liu, Yiran Huang
Castration-resistant prostate cancer (CRPC) is an advanced form of prostate cancer. Despite some progresses have been made, the mechanism of CRPC development is still largely unknown, including the genes involved in its development have not been well defined. Here, we identifiedPRKAR2B to be a gene over-expressingin castration-resistant prostate cancer by analyzing the different online databases. Followed functional validation experiments showed that PRKAR2B promoted CRPC cell proliferation and invasion, and inhibited CRPC cell apoptosis...
December 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27997828/a-mechanism-for-controlled-breakage-of-under-replicated-chromosomes-during-mitosis
#9
Heike Duda, Meret Arter, Jiradet Gloggnitzer, Federico Teloni, Philipp Wild, Miguel G Blanco, Matthias Altmeyer, Joao Matos
While DNA replication and mitosis occur in a sequential manner, precisely how cells maintain their temporal separation and order remains elusive. Here, we unveil a double-negative feedback loop between replication intermediates and an M-phase-specific structure-selective endonuclease, MUS81-SLX4, which renders DNA replication and mitosis mutually exclusive. MUS81 nuclease is constitutively active throughout the cell cycle but requires association with SLX4 for efficient substrate targeting. To preclude toxic processing of replicating chromosomes, WEE1 kinase restrains CDK1 and PLK1-mediated MUS81-SLX4 assembly during S phase...
December 19, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27992122/phosphatase-stable-phosphoamino-acid-mimetics-that-enhance-binding-affinities-with-the-polo-box-domain-of-polo-like-kinase-1
#10
David Hymel, Terrence Burke
(2S,3R)-2-Amino-3-methyl-4-phosphono-butanoic acid (Pmab) is a phosphatase-stable analog of phosphothreonine (pThr), which has been used in a variety of biological contexts. These include peptidomimetic ligands that bind to the polo-box domain (PBD) of polo-like kinase 1 (Plk1) with affinities approaching that of the corresponding pThr-containing peptides. However, Pmab is not widely used, because there are no direct, high-yield preparations of suitably protected reagents. We have now achieved an efficient synthesis of protected Pmab, as well as variants with different substituents at the 3R-center...
December 19, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27987384/salmonella-typhimurium-ptsj-is-a-novel-mocr-like-transcriptional-repressor-involved-in-regulating-the-vitamin-b6-salvage-pathway
#11
Angela Tramonti, Teresa Milano, Caterina Nardella, Martino L di Salvo, Stefano Pascarella, Roberto Contestabile
The vitamin B6 salvage pathway, involving pyridoxine 5'-phosphate oxidase (PNPOx) and pyridoxal kinase (PLK), recycles B6 vitamers from nutrients and protein turnover to produce pyridoxal 5'-phosphate (PLP), the catalytically active form of the vitamin. Regulation of this pathway, widespread in living organisms including humans and many bacteria, is very important to vitamin B6 homeostasis but poorly understood. Although some information is available on the enzymatic regulation of PNPOx and PLK, little is known on their regulation at the transcriptional level...
December 17, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27979967/daz-interacting-protein-1-dzip1-phosphorylation-by-polo-like-kinase-1-plk1-regulates-the-centriolar-satellites-localization-of-the-bbsome-during-the-cell-cycle
#12
Boyan Zhang, Gang Wang, Xiaowei Xu, Sisi Yang, Tenghan Zhuang, Guopeng Wang, He Ren, Steven Y Cheng, Qing Jiang, Chuanmao Zhang
The function of the primary cilia, which is assembled in most vertebrate cells, is achieved by transport in and out of kinds of signaling receptors. The BBSome protein complex could recognize and target membrane proteins to the cilia, but how the BBSome itself is transported into the cilia is poorly understood. Here we demonstrate that the centrosome protein Dzip1 mediates the assembly of the BBSome-Dzip1-PCM1 complex in the centriolar satellites (CS) at the G0 phase for ciliary translocation of the BBSome...
December 15, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27965426/mitotic-phosphotyrosine-network-analysis-reveals-that-tyrosine-phosphorylation-regulates-polo-like-kinase-1-plk1
#13
Danielle Caron, Dominic P Byrne, Philippe Thebault, Denis Soulet, Christian R Landry, Patrick A Eyers, Sabine Elowe
Tyrosine phosphorylation is closely associated with cell proliferation. During the cell cycle, serine and threonine phosphorylation plays the leading role, and such phosphorylation events are most dynamic during the mitotic phase of the cell cycle. However, mitotic phosphotyrosine is not well characterized. Although a few functionally-relevant mitotic phosphotyrosine sites have been characterized, evidence suggests that this modification may be more prevalent than previously appreciated. Here, we examined tyrosine phosphorylation in mitotic human cells including those on spindle-associated proteins...
December 13, 2016: Science Signaling
https://www.readbyqxmd.com/read/27956081/gene-markers-of-fracture-healing-in-early-stage-and-the-regulatory-mechanism-during-the-process-using-microarray-analysis
#14
Chengxue Wang, Baochang Qi, Lei Tan, Jieping Cheng
BACKGROUND: The aim of this study was to explore crucial markers and uncover the regulatory mechanisms of fracture healing in the early stage. METHODS: Gene expression profile of GSE45156 was downloaded, in which 3 fractured samples and 3 unfractured samples were used in our present study. Based on the threshold value, differentially expressed genes (DEGs) were selected between two kinds of samples using limma package in R. Enrichment analysis of these DEGs was performed by DAVID software...
December 9, 2016: Acta Orthopaedica et Traumatologica Turcica
https://www.readbyqxmd.com/read/27941070/phosphorylation-of-pp1-regulator-sds22-by-plk1-ensures-accurate-chromosome-segregation
#15
Hequan Duan, Chunli Wang, Ming Wang, Xinjiao Gao, Maomao Yan, Saima Akram, Wei Peng, Hanfa Zou, Dong Wang, Jiajia Zhou, Youjun Chu, Zhen Dou, Gregory Barrett, Hadiyah-Nicole Green, Fangjun Wang, Ruijun Tian, Ping He, Wenwen Wang, Xing Liu, Xuebiao Yao
No abstract text is available yet for this article.
December 9, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27922680/identification-of-key-genes-induced-by-platelet-rich-plasma-in-human-dermal-papilla-cells-using-bioinformatics-methods
#16
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...
January 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27904765/volasertib-suppresses-the-growth-of-human-hepatocellular-carcinoma-in-vitro-and-in-vivo
#17
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/27902479/identification-of-a-novel-polo-like-kinase-1-inhibitor-that-specifically-blocks-the-functions-of-polo-box-domain
#18
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
#19
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
#20
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
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