18 results match your criteria source plk1

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Dysregulated G2 phase checkpoint recovery pathway reduces DNA repair efficiency and increases chromosomal instability in a wide range of tumours.

Oncogenesis 2021 May 15;10(5):41. Epub 2021 May 15.

Mater Research Institute-The University of Queensland, Brisbane, QLD, Australia.

Defective DNA repair is being demonstrated to be a useful target in cancer treatment. Currently, defective repair is identified by specific gene mutations, however defective repair is a common feature of cancers without these mutations. DNA damage triggers cell cycle checkpoints that are responsible for co-ordinating cell cycle arrest and DNA repair. Read More

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METTL3-mediated mA modification regulates cell cycle progression of dental pulp stem cells.

Stem Cell Res Ther 2021 Mar 1;12(1):159. Epub 2021 Mar 1.

Stomatological Hospital, Southern Medical University, Guangzhou, 510280, China.

Background: Dental pulp stem cells (DPSCs) are a promising cell source in endodontic regeneration and tissue engineering with limited self-renewal and pluripotency capacity. N-methyladenosine (mA) is the most prevalent, reversible internal modification in RNAs associated with stem cell fate determination. In this study, we aim to explore the biological effect of mA methylation in DPSCs. Read More

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Discovery of Targeted Covalent Natural Products against PLK1 by Herb-Based Screening.

J Chem Inf Model 2020 09 28;60(9):4350-4358. Epub 2020 May 28.

BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

Natural products (NPs) are a rich source of drug discovery, and some of them act by covalently binding to the targets. Recently, targeted covalent natural product (TCNP) design has gained considerable attention since this approach offers significant benefits in improving biological efficacy and decreasing the off-target side effects. However, most of the known TCNPs were discovered by chance. Read More

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September 2020

CDK1 and PLK1 coordinate the disassembly and reassembly of the nuclear envelope in vertebrate mitosis.

Oncotarget 2018 Jan 23;9(8):7763-7773. Epub 2017 Dec 23.

College of Health and Life Science, Research Institute for Environment Health and Society, Brunel University London, UB8 3PH, UK.

Micronuclei (MN) arise from chromosomes or fragments that fail to be incorporated into the primary nucleus after cell division. These structures are a major source of genetic instability caused by DNA repair and replication defects coupled to aberrant Nuclear Envelope (NE). These problems ultimately lead to a spectrum of chromosome rearrangements called chromothripsis, a phenomenon that is a hallmark of several cancers. Read More

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January 2018

Structure-Bioactivity Relationship for Benzimidazole Thiophene Inhibitors of Polo-Like Kinase 1 (PLK1), a Potential Drug Target in Schistosoma mansoni.

PLoS Negl Trop Dis 2016 Jan 11;10(1):e0004356. Epub 2016 Jan 11.

Center for Discovery and Innovation in Parasitic Diseases, University of California, San Francisco, San Francisco, California, United States of America.

Background: Schistosoma flatworm parasites cause schistosomiasis, a chronic and debilitating disease of poverty in developing countries. Praziquantel is employed for treatment and disease control. However, its efficacy spectrum is incomplete (less active or inactive against immature stages of the parasite) and there is a concern of drug resistance. Read More

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January 2016

Rice SNF2 family helicase ENL1 is essential for syncytial endosperm development.

Plant J 2015 Jan 11;81(1):1-12. Epub 2014 Nov 11.

Bioscience and Biotechnology Center, Nagoya University, Nagoya, 464-8601, Japan.

The endosperm of cereal grains represents the most important source of human nutrition. In addition, the endosperm provides many investigatory opportunities for biologists because of the unique processes that occur during its ontogeny, including syncytial development at early stages. Rice endospermless 1 (enl1) develops seeds lacking an endosperm but carrying a functional embryo. Read More

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January 2015

Crystal structure of triple-BRCT-domain of ECT2 and insights into the binding characteristics to CYK-4.

FEBS Lett 2014 Aug 25;588(17):2911-20. Epub 2014 Jul 25.

Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China. Electronic address:

Homo sapiens ECT2 is a cell cycle regulator that plays critical roles in cytokinesis. ECT2 activity is restrained during interphase via intra-molecular interactions that involve its N-terminal triple-BRCT-domain and its C-terminal DH-PH domain. At anaphase, this self-inhibitory mechanism is relieved by Plk1-phosphorylated CYK-4, which directly engages the ECT2 BRCT domain. Read More

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A screen of zebrafish mutants identifies ethanol-sensitive genetic loci.

Alcohol Clin Exp Res 2014 Mar 24;38(3):694-703. Epub 2013 Oct 24.

Waggoner Center for Alcohol & Addiction Research, Institute for Cell and Molecular Biology, University of Texas at Austin, Austin, Texas.

Background: Fetal alcohol spectrum disorders (FASD) are a highly variable set of phenotypes caused by fetal alcohol exposure. Numerous factors influence FASD phenotypes, including genetics. The zebrafish is a powerful vertebrate model system with which to identify these genetic factors. Read More

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Inhibition of polo-like kinase 1 induces cell cycle arrest and sensitizes glioblastoma cells to ionizing radiation.

Cancer Biother Radiopharm 2013 Sep 28;28(7):516-22. Epub 2013 May 28.

Department of Genetics, University of São Paulo, Brazil.

Despite efforts to improve surgical, radiologic, and chemotherapeutic strategies, the outcome of patients with glioblastoma (GBM) is still poor. Polo-like kinase 1 (PLK1) is a serine/threonine kinase that plays key roles in cell cycle control and has been associated with tumor growth and prognosis. Here, we aimed at testing the radiosensitizing effects of the PLK1 inhibitor BI 2536 on eight GBM cell lines. Read More

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September 2013

Identification of novel compounds that enhance colon cancer cell sensitivity to inflammatory apoptotic ligands.

Cancer Biol Ther 2013 May 1;14(5):436-49. Epub 2013 Feb 1.

Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA.

Immune and inflammatory death ligands expressed within neoplastic tissue could potentially target apoptosis to transformed cells. To develop approaches that accentuate the anti-cancer potential of the inflammatory response, the Chembridge DIVERSet (TM) library was screened for compounds that accentuated apoptosis in a strictly TNF-dependent manner. We identified a number of novel compounds with this activity, the most active of these, AK3 and AK10, sensitized colon cancer cells to TNF at 0. Read More

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DNA replication stress response involving PLK1, CDC6, POLQ, RAD51 and CLASPIN upregulation prognoses the outcome of early/mid-stage non-small cell lung cancer patients.

Oncogenesis 2012 Oct 22;1:e30. Epub 2012 Oct 22.

1] Cancer Research Center of Toulouse, Inserm U1037, CNRS ERL5294, University of Toulouse, University Paul Sabatier, Toulouse, France [2] Rangueil-Larrey University Hospital, University of Toulouse, University Paul Sabatier, Toulouse, France.

Lung cancer is the leading cause of cancer deaths worldwide. Clinical staging classification is generally insufficient to provide a reliable prognosis, particularly for early stages. In addition, prognostic factors are therefore needed to better forecast life expectancy and optimize adjuvant therapeutic strategy. Read More

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October 2012

Cohesion fatigue induces chromatid separation in cells delayed at metaphase.

Curr Biol 2011 Jun 9;21(12):1018-24. Epub 2011 Jun 9.

Program in Cell Cycle and Cancer Biology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.

Background: Chromosome instability is thought to be a major contributor to cancer malignancy and birth defects. For balanced chromosome segregation in mitosis, kinetochores on sister chromatids bind and pull on microtubules emanating from opposite spindle poles. This tension contributes to the correction of improper kinetochore attachments and is opposed by the cohesin complex that holds the sister chromatids together. Read More

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NMS-P937, a 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivative as potent and selective Polo-like kinase 1 inhibitor.

Bioorg Med Chem Lett 2011 May 21;21(10):2969-74. Epub 2011 Mar 21.

Nerviano Medical Sciences srl, Business Unit Oncology, Viale Pasteur 10, 20014 Nerviano, MI, Italy.

As part of our drug discovery effort, we identified and developed 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as PLK1 inhibitors. We now report the optimization of this class that led to the identification of NMS-P937, a potent, selective and orally available PLK1 inhibitor. Also, in order to understand the source of PLK1 selectivity, we determined the crystal structure of PLK1 with NMS-P937. Read More

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Depsides isolated from the Sri Lankan lichen Parmotrema sp. exhibit selective Plk1 inhibitory activity.

Pharm Biol 2011 Mar 1;49(3):296-301. Epub 2011 Feb 1.

Departments of Chemistry and Earth & Ocean Sciences, University of British Columbia, Vancouver, British Columbia, Canada.

Context: Mitotic kinase enzymes regulate critical stages of mitosis and are amenable to pharmacological inhibition. Since natural products have been a rich source of antimitotic inhibitors, we postulated that natural products would also provide effective inhibitors of mitotic kinases.

Objective: To explore unique marine and terrestrial natural product sources for new anticancer drug leads, we screened our natural product extract library for polo-like kinase-1 (Plk1) kinase inhibitors. Read More

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The Plk1-dependent phosphoproteome of the early mitotic spindle.

Mol Cell Proteomics 2011 Jan 22;10(1):M110.004457. Epub 2010 Sep 22.

Department of Cell Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.

Polo-like kinases regulate many aspects of mitotic and meiotic progression from yeast to man. In early mitosis, mammalian Polo-like kinase 1 (Plk1) controls centrosome maturation, spindle assembly, and microtubule attachment to kinetochores. However, despite the essential and diverse functions of Plk1, the full range of Plk1 substrates remains to be explored. Read More

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January 2011

Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation.

Nature 2010 Mar;464(7288):606-9

Center of Regenerative Medicine in Barcelona, Spain.

Although mammalian hearts show almost no ability to regenerate, there is a growing initiative to determine whether existing cardiomyocytes or progenitor cells can be coaxed into eliciting a regenerative response. In contrast to mammals, several non-mammalian vertebrate species are able to regenerate their hearts, including the zebrafish, which can fully regenerate its heart after amputation of up to 20% of the ventricle. To address directly the source of newly formed cardiomyocytes during zebrafish heart regeneration, we first established a genetic strategy to trace the lineage of cardiomyocytes in the adult fish, on the basis of the Cre/lox system widely used in the mouse. Read More

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Crystallization and preliminary X-ray diffraction studies on the human Plk1 Polo-box domain in complex with an unphosphorylated and a phosphorylated target peptide from Cdc25C.

Acta Crystallogr Sect F Struct Biol Cryst Commun 2006 Apr 25;62(Pt 4):372-5. Epub 2006 Mar 25.

Structural Biology and Biocomputing Programme, Spanish National Cancer Centre (CNIO) Macromolecular Crystallography Group, c/Melchor Fdez Almagro 3, 28029 Madrid, Spain.

Polo-like kinase (Plk1) is crucial for cell-cycle progression via mitosis. Members of the Polo-like kinase family are characterized by the presence of a C-terminal domain termed the Polo-box domain (PBD) in addition to the N-terminal kinase domain. The PBD of Plk1 was cloned and overexpressed in Escherichia coli. Read More

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Cell cycle dependent expression of Plk1 in synchronized porcine fetal fibroblasts.

Mol Reprod Dev 2003 Jul;65(3):245-53

Institute of Animal Physiology and Genetics, Libechov, Czech Republic.

Enzymes of the Polo-like kinase (Plk) family are active in the pathways controlling mitosis in several species. We have cloned cDNA fragments of the porcine homologues of Plk1, Plk2, and Plk3 employing fetal fibroblasts as source. All three partial cDNAs showed high sequence homology with their mouse and human counterparts and contained the Polo box, a domain characteristic for all Polo kinases. Read More

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