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Polo-like kinase

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https://www.readbyqxmd.com/read/28330257/generation-of-an-inducible-system-to-express-polo-like-kinase-cdc5-as-tap-fusion-protein-during-meiosis-in-saccharomyces-cerevisiae
#1
Rajni Vaid, Kamal Dev, Michael Lichten, Anuradha Sourirajan
Tandem affinity purification (TAP) is a highly efficient method for isolation of protein complexes from endogenous biological macromolecules. TAP system consists of dual affinity tags that facilitates the sequential purification of the desired proteins expressed at their low levels in vivo. Polo-like kinases (PLK) are serine/threonine protein kinases that are the crucial regulators of cell cycle. Cdc5, the solitary PLK in budding yeast Saccharomyces cerevisiae, has diverse array of targets in cell cycle. The present study was undertaken to construct an estrogen-inducible system for expression of Cdc5-TAP to isolate the substrates of Cdc5 during meiosis, particularly, pachytene stage of meiosis I...
December 2016: 3 Biotech
https://www.readbyqxmd.com/read/28314279/comparative-analysis-of-a-fret-based-plk1-kinase-assay-to-identify-plk1-inhibitors-for-chemotherapy
#2
Sol-Bi Shin, Sang-Uk Woo, Young-Joo Lee, Hyungshin Yim
Advanced techniques for detecting kinase inhibitors are in demand due to limitations of traditional approaches. Here, we used a fluorescence resonance energy transfer (FRET)-based kinase assay, a sensitive fluorescence turn-on biosensing platform, to identify a Polo-like kinase 1 (PLK1) inhibitor. The assay was developed with the Z'-Lyte™ FRET-peptide and PLK1 kinase purified from a baculovirus expression system. Using PLK1 inhibitors, sensitivity and efficiency of this FRET-based PLK1 kinase assay were compared to those of radioisotope-based and immunoblot-based assays...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28296906/anticancer-activity-of-a-novel-small-molecule-tubulin-inhibitor-stk899704
#3
Krisada Sakchaisri, Sun-Ok Kim, Joonsung Hwang, Nak Kyun Soung, Kyung Ho Lee, Tae Woong Choi, Yongjun Lee, Chan-Mi Park, Naraganahalli R Thimmegowda, Phil Young Lee, Bettaswamigowda Shwetha, Ganipisetti Srinivasrao, Thi Thu Huong Pham, Jae-Hyuk Jang, Hye-Won Yum, Young-Joon Surh, Kyung S Lee, Hwangseo Park, Seung Jun Kim, Yong Tae Kwon, Jong Seog Ahn, Bo Yeon Kim
We have identified the small molecule STK899704 as a structurally novel tubulin inhibitor. STK899704 suppressed the proliferation of cancer cell lines from various origins with IC50 values ranging from 0.2 to 1.0 μM. STK899704 prevented the polymerization of purified tubulin in vitro and also depolymerized microtubule in cultured cells leading to mitotic arrest, associated with increased Cdc25C phosphorylation and the accumulation of both cyclin B1 and polo-like kinase 1 (Plk1), and apoptosis. Unlike many anticancer drugs such as Taxol and doxorubicin, STK899704 effectively displayed antiproliferative activity against multidrug-resistant cancer cell lines...
2017: PloS One
https://www.readbyqxmd.com/read/28296169/pyrrole-based-macrocyclic-small-molecule-inhibitors-targeting-oocyte-maturation
#4
Jeong Kyu Bang, Pethaiah Gunasekaran, So Rim Lee, Seung-Min Jeong, Jeong-Woo Kwon, Toshiki Takei, Yuya Asahina, Geul Bang, Seongnyeon Kim, Mija Ahn, Eun Kyung Ryu, Hak Nam Kim, Ki-Yub Nam, Song Yub Shin, Hironobu Hojo, Suk Namgoong, Nam-Hyung Kim
Polo-like kinase 1 (PLK1) plays crucial roles in various stages of oocyte maturation. Recently, we reported that the peptidomimetic AB103-8 that targets polo box domain (PBD) of PLK1 affected oocyte meiotic maturation and meiosis resumption. However, to overcome the peptidic drawbacks, we designed and synthesized a series of pyrrole-based small-molecule inhibitors and screened against porcine oocyte maturation rates. Among them, compound 4 showed the highest inhibitory activity with enhanced inhibition against the embryos blastocyst formation...
March 12, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28287096/blockade-of-vascular-endothelial-growth-factor-receptors-by-tivozanib-has-potential-anti-tumour-effects-on-human-glioblastoma-cells
#5
Majid Momeny, Farima Moghaddaskho, Narges K Gortany, Hassan Yousefi, Zahra Sabourinejad, Ghazaleh Zarrinrad, Shahab Mirshahvaladi, Haniyeh Eyvani, Farinaz Barghi, Leila Ahmadinia, Mahmoud Ghazi-Khansari, Ahmad R Dehpour, Saeid Amanpour, Seyyed M Tavangar, Leila Dardaei, Amir H Emami, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
Glioblastoma (GBM) remains one of the most fatal human malignancies due to its high angiogenic and infiltrative capacities. Even with optimal therapy including surgery, radiotherapy and temozolomide, it is essentially incurable. GBM is among the most neovascularised neoplasms and its malignant progression associates with striking neovascularisation, evidenced by vasoproliferation and endothelial cell hyperplasia. Targeting the pro-angiogenic pathways is therefore a promising anti-glioma strategy. Here we show that tivozanib, a pan-inhibitor of vascular endothelial growth factor (VEGF) receptors, inhibited proliferation of GBM cells through a G2/M cell cycle arrest via inhibition of polo-like kinase 1 (PLK1) signalling pathway and down-modulation of Aurora kinases A and B, cyclin B1 and CDC25C...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28286049/insulin-signaling-regulates-the-foxm1-plk1-cenp-a-pathway-to-promote-adaptive-pancreatic-%C3%AE-%C3%A2-cell-proliferation
#6
Jun Shirakawa, Megan Fernandez, Tomozumi Takatani, Abdelfattah El Ouaamari, Prapaporn Jungtrakoon, Erin R Okawa, Wei Zhang, Peng Yi, Alessandro Doria, Rohit N Kulkarni
Investigation of cell-cycle kinetics in mammalian pancreatic β cells has mostly focused on transition from the quiescent (G0) to G1 phase. Here, we report that centromere protein A (CENP-A), which is required for chromosome segregation during the M-phase, is necessary for adaptive β cell proliferation. Receptor-mediated insulin signaling promotes DNA-binding activity of FoxM1 to regulate expression of CENP-A and polo-like kinase-1 (PLK1) by modulating cyclin-dependent kinase-1/2. CENP-A deposition at the centromere is augmented by PLK1 to promote mitosis, while knocking down CENP-A limits β cell proliferation and survival...
February 26, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28285924/enhancing-polo-like-kinase-1-selectivity-of-polo-box-domain-binding-peptides
#7
Xue Zhi Zhao, David Hymel, Terrence R Burke
An important goal in the development of polo-like kinase 1 (Plk1) polo-box domain (PBD) binding inhibitors is selectivity for Plk1 relative to Plk2 and Plk3. In our current work we show that Plk1 PBD selectivity can be significantly enhanced by modulating interactions within a previously discovered "cryptic pocket" and a more recently identified proximal "auxiliary pocket."
February 28, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28283778/plk1-associated-micrornas-are-correlated-with-pediatric-medulloblastoma-prognosis
#8
Julia Alejandra Pezuk, María Sol Brassesco, Ricardo Santos de Oliveira, Hélio Rubens Machado, Luciano Neder, Carlos Alberto Scrideli, Luiz Gonzaga Tone
PURPOSE: Medulloblastoma (MB) is the most common malignant tumor of the central nervous system (CNS) in children. Despite its relative good survival rates, treatment can cause long time sequels and may impair patients' lifespan and quality, making the search for new treatment options still necessary. Polo like kinases (PLKs) constitute a five-member serine/threonine kinases family (PLK 1-5) that regulates different stages during cell cycle. Abnormal PLKs expression has been observed in several cancer types, including MB...
March 10, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28270075/comparative-effects-of-polo-like-kinase-1-inhibitors-as-monotherapy-and-in-combination-with-current-treatments-for-medulloblastoma
#9
Julia Alejandra Pezuk, Maria Sol Brassesco, Priscila Maria Manzini Ramos, Carlos Alberto Scrideli, Luiz Gonzaga Tone
BACKGROUND: Medulloblastoma (MB) is one of most frequent malignant tumors that affects children. Despite relative good survival rates, long time sequels are still significant and represent a challenge for treatment of MB patients. Therefore, in an attempt to reduce treatment aftereffects new therapeutic targets are constantly being explored. Polo like kinase 1 (PLK1) is a master cell cycle regulator that has been reported increased in proliferative cells, while its depletion has been repeatedly proposed as an oncological therapeutic strategy...
February 13, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28257888/polo-like-kinase-2-phosphorylation-of-amyloid-precursor-protein-regulates-activity-dependent-amyloidogenic-processing
#10
Yeunkum Lee, Ji Soo Lee, Kea Joo Lee, R Scott Turner, Hyang-Sook Hoe, Daniel T S Pak
Alzheimer's disease (AD) is a neurodegenerative disorder with cognitive deficits. Amyloidogenic processing of amyloid precursor protein (APP) produces amyloid β (Aβ), the major component of hallmark AD plaques. Synaptic activity stimulates APP cleavage, whereas APP promotes excitatory synaptic transmission, suggesting APP participates in neuronal homeostasis. However, mechanisms linking synaptic activity to APP processing are unclear. Here we show that Polo-like kinase 2 (Plk2), an activity-inducible regulator of homeostatic plasticity, directly binds and phosphorylates threonine-668 and serine-675 of APP in vitro and associates with APP in vivo...
March 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28249986/coordination-of-double-strand-break-repair-and-meiotic-progression-in-yeast-by-a-mek1-ndt80-negative-feedback-loop
#11
Evelyn Prugar, Cameron Burnett, Xiangyu Chen, Nancy M Hollingsworth
During meiosis, homologous chromosomes are physically connected by crossovers and sister chromatid cohesion. Interhomolog crossovers are generated by the highly regulated repair of programmed double strand breaks (DSBs). The meiosis-specific kinase, Mek1, is critical for this regulation. Mek1 down-regulates the mitotic recombinase Rad51, indirectly promoting interhomolog strand invasion by the meiosis-specific recombinase, Dmc1. Mek1 also promotes the formation of crossovers that are distributed throughout the genome by interference and is the effector kinase for a meiosis-specific checkpoint that delays entry into Meiosis I until DSBs have been repaired...
March 1, 2017: Genetics
https://www.readbyqxmd.com/read/28249963/cell-death-response-to-anti-mitotic-drug-treatment-in-cell-culture-mouse-tumor-model-and-the-clinic
#12
Jue Shi, Timothy J Mitchison
Anti-mitotic cancer drugs include classic microtubule-targeting drugs, such as taxanes and vinca alkaloids, and the newer spindle-targeting drugs, such as inhibitors of the motor protein, Kinesin-5 (aka KSP, Eg5, KIF11), and Aurora-A, Aurora-B and Polo-like kinases. Microtubule-targeting drugs are among the first line of chemotherapies for a wide spectrum of cancers, but patient responses vary greatly. We still lack understanding of how these drugs achieve a favorable therapeutic index, and why individual patient responses vary...
March 1, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28238495/maternal-common-variant-rs2305957-spanning-plk4-is-associated-with-blastocyst-formation-and-early-recurrent-miscarriage
#13
Qian Zhang, Guangyu Li, Lei Zhang, Xiaohe Sun, Dandan Zhang, Juanjuan Lu, Jinlong Ma, Junhao Yan, Zi-Jiang Chen
OBJECTIVE: To investigate whether the common variant rs2305957 spanning PLK4 (Polo-like kinase 4) confers risk to embryo development in Northern Chinese Han (CHN) women. DESIGN: Genetic association study. SETTING: University hospital. PATIENT(S): A total of 2,015 infertile women who underwent in vitro fertilization (IVF), 530 women with early recurrent miscarriage (ERM), and 600 fertile control women in the CHN population...
February 23, 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/28235541/targeted-knockdown-of-polo-like-kinase-1-alters-metabolic-regulation-in-melanoma
#14
Rosie Elizabeth Ann Gutteridge, Chandra K Singh, Mary Ann Ndiaye, Nihal Ahmad
A limited number of studies have indicated an association of the mitotic kinase polo-like kinase 1 (PLK1) and cellular metabolism. Here, employing an inducible RNA interference approach in A375 melanoma cells coupled with a PCR array and multiple validation approaches, we demonstrated that PLK1 alters a number of genes associated with cellular metabolism. PLK1 knockdown resulted in a significant downregulation of IDH1, PDP2 and PCK1 and upregulation of FBP1. Ingenuity Pathway Analysis (IPA) identified that 1) glycolysis and the pentose phosphate pathway are major canonical pathways associated with PLK1, and 2) PLK1 inhibition-modulated genes were largely associated with cellular proliferation, with FBP1 being the key modulator...
February 22, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28229117/dna-methylation-data-for-identification-of-epigenetic-targets-of-resveratrol-in-triple-negative-breast-cancer-cells
#15
Rubiceli Medina-Aguilar, Carlos Pérez-Plasencia, Patricio Gariglio, Laurence A Marchat, Ali Flores-Pérez, César López-Camarillo, Jaime García Mena
Previous studies revealed that some bioactive food components have anti-cancer effects. However epigenetic effects of dietary compound resveratrol are largely unknown in breast cancer cells (M.A. Dawson, T. Kouzarides, 2012) [1]. Here we provide novel data and comparisons of DNA methylation status of promoter gene regions in response to resveratrol treatment at 24 h and 48 h versus untreated MDA-MB-231 breast cancer cells. DNA methylation changes were measured using Array-PRIMES method (aPRIMES) followed by whole-genome hybridization using human DNA methylation promoter microarray NimbleGen HG18 Refseq Promoter 3×720 K array...
April 2017: Data in Brief
https://www.readbyqxmd.com/read/28228549/the-budding-yeast-polo-like-kinase-localizes-to-distinct-populations-at-centrosomes-during-mitosis
#16
Vladimir V Botchkarev, Mikael V Garabedian, Brenda Lemos, Eric Paulissen, James E Haber
The budding yeast Polo-like kinase Cdc5 is a key regulator of many mitotic events. Cdc5 coordinates its functions spatially and temporally by changing its localization during the cell cycle: Cdc5 is imported into the nucleus in G2 phase and is released to the cytoplasm in anaphase, where it accumulates at the bud neck. Cdc5 also localizes to the spindle pole bodies (SPBs) from S phase until the end of mitosis. Whether Cdc5 changes its SPB population during the cell cycle is not known. We find that Cdc5 localizes to distinct SPB subpopulations depending on the mitotic stage...
February 22, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28223799/hypoxia-responsive-ionizable-liposome-delivery-sirna-for-glioma-therapy
#17
Hong-Mei Liu, Ya-Fei Zhang, Yan-Dong Xie, Yi-Fan Cai, Bai-Yang Li, Wen Li, Ling-Yu Zeng, Yu-Ling Li, Ru-Tong Yu
Here, we report the hypoxia-responsive ionizable liposomes to deliver small interference RNA (siRNA) anticancer drugs, which can selectively enhance cellular uptake of the siRNA under hypoxic and low-pH conditions to cure glioma. For this purpose, malate dehydrogenase lipid molecules were synthesized, which contain nitroimidazole groups that impart hypoxia sensitivity and specificity as hydrophobic tails, and tertiary amines as hydrophilic head groups. These malate dehydrogenase molecules, together with DSPE-PEG2000 and cholesterol, were self-assembled into O'(1),O(1)-(3-(dimethylamino)propane-1,2-diyl) 16-bis(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl) di(hexadecanedioate) liposomes (MLP) to encapsulate siRNA through electrostatic interaction...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28212994/an-open-label-phase-ii-study-of-the-polo-like-kinase-1-plk-1-inhibitor-bi-2536-in-patients-with-relapsed-small-cell-lung-cancer-sclc
#18
Mark M Awad, Quincy S-C Chu, Leena Gandhi, Joe J Stephenson, Ramaswamy Govindan, Daniel S Bradford, Philip D Bonomi, David M Ellison, Keith D Eaton, Holger Fritsch, Gerd Munzert, Bruce E Johnson, Mark A Socinski
OBJECTIVES: This phase II, open-label study was designed to evaluate the response rate to the polo-like kinase 1 (Plk-1) inhibitor BI 2536 in patients with sensitive-relapsed small cell lung cancer (SCLC). Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response, and safety. MATERIALS AND METHODS: Patients were treated with the recommended phase II dose of 200mg of BI 2536 intravenously every 21days. This was a two-stage design with an early stopping rule in place if responses were not seen in at least 2 of the first 18 enrolled patients...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28185436/corrigendum-phosphatase-stable-phosphoamino-acid-mimetics-that-enhance-binding-affinities-with-the-polo-box-domain-of-polo-like-kinase%C3%A2-1
#19
David Hymel, Terrence R Burke
No abstract text is available yet for this article.
February 3, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28184925/inhibiting-plk1-induces-autophagy-of-acute-myeloid-leukemia-cells-via-mammalian-target-of-rapamycin-pathway-dephosphorylation
#20
Yan-Fang Tao, Zhi-Heng Li, Wei-Wei Du, Li-Xiao Xu, Jun-Li Ren, Xiao-Lu Li, Fang Fang, Yi Xie, Mei Li, Guang-Hui Qian, Yan-Hong Li, Yi-Ping Li, Gang Li, Yi Wu, Xing Feng, Jian Wang, Wei-Qi He, Shao-Yan Hu, Jun Lu, Jian Pan
Decreased autophagy is accompanied by the development of a myeloproliferative state or acute myeloid leukemia (AML). AML cells are often sensitive to autophagy‑inducing stimuli, prompting the idea that targeting autophagy can be useful in AML cytotoxic therapy. AML NB4 cells overexpressing microtubule-associated protein 1 light chain 3-green fluorescent protein were screened with 69 inhibitors to analyze autophagy activity. AML cells were treated with the polo-like kinase 1 (PLK1) inhibitors RO3280 and BI2536 before autophagy analysis...
March 2017: Oncology Reports
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