Read by QxMD icon Read

Polo-like kinase

Daibiao Xiao, Ming Yue, Hexiu Su, Ping Ren, Jue Jiang, Feng Li, Yufeng Hu, Haining Du, Hudan Liu, Guoliang Qing
MYCN amplification in human cancers predicts poor prognosis and resistance to therapy. However, pharmacological strategies that directly target N-Myc, the protein encoded by MYCN, remain elusive. Here, we identify a molecular mechanism responsible for reciprocal activation between Polo-like kinase-1 (PLK1) and N-Myc. PLK1 specifically binds to the SCF(Fbw7) ubiquitin ligase, phosphorylates it, and promotes its autopolyubiquitination and proteasomal degradation, counteracting Fbw7-mediated degradation of N-Myc and additional substrates, including cyclin E and Mcl1...
October 4, 2016: Molecular Cell
Wayne Ng, Joo-Shik Shin, Bin Wang, Cheok Soon Lee
No abstract text is available yet for this article.
February 2016: Pathology
Wayne Ng, Joo-Shik Shin, Tao Yang, Tara Roberts, Bin Wang, Jarrad Begg, Cheok Soon Lee
No abstract text is available yet for this article.
February 2016: Pathology
Irena Zurnic, Sylvia Hütter, Ute Rzeha, Roger Helbig, Nicole Stanke, Juliane Reh, Erik Müllers, Martin V Hamann, Tobias Kern, Gesche K Gerresheim, Fabian Lindel, Erik Serrao, Paul Lesbats, Alan N Engelman, Peter Cherepanov, Dirk Lindemann
[This corrects the article DOI: 10.1371/journal.ppat.1005860.].
October 2016: PLoS Pathogens
W Bruinsma, M Aprelia, I García-Santisteban, J Kool, Y J Xu, R H Medema
When cells in G2 phase are challenged with DNA damage, several key mitotic regulators such as Cdk1/Cyclin B, Aurora A and Plk1 are inhibited to prevent entry into mitosis. Here we have studied how inhibition of Plk1 is established after DNA damage. Using a Förster resonance energy transfer (FRET)-based biosensor for Plk1 activity, we show that inhibition of Plk1 after DNA damage occurs with relatively slow kinetics and is entirely dependent on loss of Plk1-T210 phosphorylation. As T210 is phosphorylated by the kinase Aurora A in conjunction with its co-factor Bora, we investigated how they are affected by DNA damage...
October 10, 2016: Oncogene
Tyler S Machovina, Rana Mainpal, Anahita Daryabeigi, Olivia McGovern, Dimitra Paouneskou, Sara Labella, Monique Zetka, Verena Jantsch, Judith L Yanowitz
Crossover (CO) recombination creates a physical connection between homologs that promotes their proper segregation at meiosis I (MI). Failure to realize an obligate CO causes homologs to attach independently to the MI spindle and separate randomly, leading to nondisjunction. However, mechanisms that determine whether homolog pairs have received crossovers remain mysterious. Here we describe a surveillance system in C. elegans that monitors recombination intermediates and couples their formation to meiotic progression...
October 1, 2016: Current Biology: CB
Andreas Ritter, Alexandra Friemel, Nina-Naomi Kreis, Frank Louwen, Juping Yuan
Polo-like kinase 1 (Plk1) has been established as one of the most promising targets for molecular anticancer intervention. In fact, various Plk1 inhibitors have been identified and characterized. While the data derived from the bench are prospective, the clinical outcomes are less encouraging by showing modest efficacy. One of the explanations for this discrepancy could be unintendedly targeting of non-malignant cells by Plk1 inhibitors. In this work, we have addressed the effect of Plk1 inhibition in adipose tissue-derived mesenchymal stem cells (ASCs)...
October 5, 2016: Oncotarget
Arancha Cebrián, Teresa Gómez Del Pulgar, Maria Jesús Fernández-Aceñero, Aurea Borrero-Palacios, Laura Del Puerto-Nevado, Javier Martínez-Useros, Juan Pablo Marín-Arango, Cristina Caramés, Ricardo Vega-Bravo, María Rodríguez-Remírez, Felix Manzarbeitia, Jesús García-Foncillas
AIM: Polo-like kinase 1 (Plk1) plays a key role in mitotic cell division and DNA damage repair. It has been observed that either up-regulated or down-regulated Plk1 could induce mitotic defects that results in aneuploidy and tumorigenesis, probably depending on the context. Few previous reports have associated Plk1 expression with prognosis and response to radiotherapy in rectal carcinomas. The aim of this study is to investigate the prognostic impact of Plk1 expression and its role in predicting response to neoadjuvant cheomoradiotherapy in rectal cancer...
September 22, 2016: Pathology, Research and Practice
Yuma Nonomiya, Kohji Noguchi, Noritaka Tanaka, Takahiro Kasagaki, Kazuhiro Katayama, Yoshikazu Sugimoto
Polo-like kinase (PLK) is a cell-cycle regulator that is overexpressed in several cancer cell types. PLK is considered a novel target for cancer therapies, and several PLK inhibitors (PLKis), including BI 2536, BI 6727, and GSK461364, have been developed. In this study, we established five BI 2536-resistant cell lines from human colorectal cancer HCT 116 cells, to explore the resistance mechanism and identify predictable biomarkers of PLKis. We demonstrated that PLKi-induced caspase-8 activation was attenuated in the BI 2536-resistant cell lines...
October 3, 2016: Cancer Science
Anuj Rathi, Riyaz Syed, Vijay Singh, Han-Seung Shin, Rahul V Patel
Cancer accounts for a numbers of deaths each year. Consequently, prevention of this deadly disease though the invention of new anticancer agents is of utmost importance. The current review elaborates the importance of indole designs as patented in the form of anticancer drug-like molecules targeting different cites of biological arena, specifically kinases such as platelet-derived growth factor receptor, vascular endothelial growth factor receptor and fibroblast growth factor receptor, Bruton's tyrosine kinase, anaplastic lymphoma kinase, Janus kinase, cyclin-dependent kinase aurora kinases A, B and C, checkpoint kinases, protein kinase R, Pim kinases, phosphoinositide 3-kinase, altered proteins kinases, polo-like kinase and many more...
October 3, 2016: Recent Patents on Anti-cancer Drug Discovery
Dongzhi Wang, Renan Chang, Gang Wang, Baoying Hu, Yong Qiang, Zhong Chen
BACKGROUND: Recent investigations have implicated that Chitosan-nucleotide nanoparticles might be useful non-viral carriers in gene therapy. Polo-like kinase 1 (PLK1) has been reported to be an important oncogene that exerted considerable therapeutic value in hepatocellular carcinoma (HCC). OBJECTIVE: We explored whether Galactosylated chitosan-graft-poly(ethylene glycol) (GCP) nanoparticle-mediated delivery of PLK1 siRNA nucleotides could serve as an effective anti-cancer agent for HCC therapy...
September 26, 2016: Anti-cancer Agents in Medicinal Chemistry
Jia Li, Ruping Wang, Olivia J Gannon, Alyssa C Rezey, Sixin Jiang, Brennan D Gerlach, Guoning Liao, Dale D Tang
Polo-like kinase 1 (Plk1) is a serine/threonine protein kinase that has been implicated in mitosis, cytokinesis and smooth muscle cell proliferation. The role of Plk1 in smooth muscle contraction has not been investigated. Here, stimulation with acetylcholine induced Plk1 phosphorylation at Thr-210 (an indication of Plk1 activation) in smooth muscle. Contractile stimulation also activated Plk1 in live smooth muscle cells as evidenced by changes in fluorescence resonance energy transfer signal of a Plk1 sensor...
September 23, 2016: Journal of Biological Chemistry
Makiko Tsutsumi, Setsuri Yokoi, Fuyuki Miya, Masafumi Miyata, Mitsuhiro Kato, Nobuhiko Okamoto, Tatsuhiko Tsunoda, Mami Yamasaki, Yonehiro Kanemura, Kenjiro Kosaki, Shinji Saitoh, Hiroki Kurahashi
It has been well documented that variants in genes encoding centrosomal proteins cause primary autosomal recessive microcephaly, although the association between centrosomal defects and the etiology of microcephaly syndromes is not fully understood. Polo-like kinase 4 (PLK4) is one of the centrosomal proteins required for centriole duplication. We here describe a patient with microcephaly and chorioretinopathy that harbors compound heterozygous missense variants, c.[442A>G]; [2336G>A], in the PLK4 gene...
September 21, 2016: European Journal of Human Genetics: EJHG
Melanie Schwermer, Sabine Dreesmann, Angelika Eggert, Kristina Althoff, Laura Steenpass, Alexander Schramm, Johannes H Schulte, Petra Temming
BACKGROUND: Retinoblastoma is the most common malignant cancer of the eye in children. While metastatic retinoblastoma is rare, cure rates for this advanced disease remain below 50%. High-level PLK1 expression in retinoblastomas has previously been shown to be correlated with adverse outcome parameters. PLK1 is a serine/threonine kinase involved in cell cycle regulation at the G2/M transition. PLK1 inhibition has been demonstrated to have anti-tumour effects in preclinical models of several paediatric tumours...
September 19, 2016: Clinical & Experimental Ophthalmology
Xue Zhi Zhao, David Hymel, Terrence R Burke
By a process involving initial screening of a set of 87 aldehydes using an oxime ligation-based strategy, we were able to achieve a several-fold affinity enhancement over one of the most potent previously known polo-like kinase 1 (Plk1) polo-box domain (PBD) binding inhibitors. This improved binding may result by accessing a newly identified auxiliary region proximal to a key hydrophobic cryptic pocket on the surface of the protein. Our findings could have general applicability to the design of PBD-binding antagonists...
October 15, 2016: Bioorganic & Medicinal Chemistry Letters
Ward G Walkup, Tara L Mastro, Leslie T Schenker, Jost Vielmetter, Rebecca Hu, Ariella Iancu, Meera Reghunathan, Barry Dylan Bannon, Mary B Kennedy
SynGAP is a Ras/Rap GTPase-activating protein (GAP) that is a major constituent of postsynaptic densities (PSDs) from mammalian forebrain. Its α1 isoform binds to all three PDZ (PSD-95, Discs-large, ZO-1) domains of PSD-95, the principal PSD scaffold, and can occupy as many as 15% of these PDZ domains. We present evidence that synGAP-α1 regulates the composition of the PSD by restricting binding to the PDZ domains of PSD-95. We show that phosphorylation by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and Polo-like kinase-2 (PLK2) decreases its affinity for the PDZ domains by several fold, which would free PDZ domains for occupancy by other proteins...
September 13, 2016: ELife
Dante Lepore, Olya Spassibojko, Gabrielle Pinto, Ruth N Collins
Intracellular trafficking is an essential and conserved eukaryotic process. Rab GTPases are a family of proteins that regulate and provide specificity for discrete membrane trafficking steps by harnessing a nucleotide-bound cycle. Global proteomic screens have revealed many Rab GTPases as phosphoproteins, but the effects of this modification are not well understood. Using the Saccharomyces cerevisiae Rab GTPase Sec4p as a model, we have found that phosphorylation negatively regulates Sec4p function by disrupting the interaction with the exocyst complex via Sec15p...
September 12, 2016: Journal of Cell Biology
Jonathan Canaani, Arnon Nagler
INTRODUCTION: Therapy for the myelodysplastic syndromes (MDS) is an evolving area of research which has made significant use of the increased understanding of the complex biology of these disorders. Novel agents targeting multiple pathogenic pathways are being actively tested in preclinical and clinical settings and hold the potential to be available to clinicians before long. AREAS COVERED: Herein we provide an historical framework for understanding the current use of hypomethylating agents in MDS and discuss recent developments in the field of targeted therapy in MDS including data from published and ongoing clinical studies with oral hypomethylating agents, PI3/polo-like kinase inhibitors, TGF-β inhibitor/ligand traps, and immune checkpoint inhibitors...
October 2016: Expert Review of Hematology
David Mahato, Dipayan Samanta, Sudit S Mukhopadhyay, R Navanietha Krishnaraj
Fanconi anemia (FA) is an autosomal recessive disorder with a high risk of malignancies including acute myeloid leukemia and squamous cell carcinoma. There is a constant search out of new potential therapeutic molecule to combat this disorder. In most cases, patients with FA develop haematological malignancies with acute myeloid leukemia and acute lymphoblastic leukemia. Identifying drugs which can efficiently block the pathways of both these disorders can be an ideal and novel strategy to treat FA. The curcumin, a natural compound obtained from turmeric is an interesting therapeutic molecule as it has been reported in the literature to combat both FA as well as leukemia...
September 8, 2016: Journal of Receptor and Signal Transduction Research
Piotr Donizy, Agnieszka Halon, Pawel Surowiak, Maciej Kaczorowski, Cyprian Kozyra, Rafal Matkowski
Polo-like kinase 1 (PLK1) is a serine-threonine kinase that plays a crucial role in the regulation of cell division. In addition, it acts as a modulator of the DNA damage response and as a novel factor in the maintenance of genome stability during DNA replication. The present study aimed to reveal the associations between PLK1 expression and clinicopathological features of patients with breast cancer (BC), particularly patient survival at 5-, 10- and 15-year follow-up. PLK1 expression was evaluated immunohistochemically in routine diagnostic tissue specimens from 83 patients treated radically for stage II BC...
September 2016: Oncology Letters
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"