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https://www.readbyqxmd.com/read/28934593/big-lessons-from-little-yeast-budding-and-fission-yeast-centrosome-structure-duplication-and-function
#1
Ann M Cavanaugh, Sue L Jaspersen
Centrosomes are a functionally conserved feature of eukaryotic cells that play an important role in cell division. The conserved γ-tubulin complex organizes spindle and astral microtubules, which, in turn, separate replicated chromosomes accurately into daughter cells. Like DNA, centrosomes are duplicated once each cell cycle. Although in some cell types it is possible for cell division to occur in the absence of centrosomes, these divisions typically result in defects in chromosome number and stability. In singlecelled organisms such as fungi, centrosomes [known as spindle pole bodies (SPBs)] are essential for cell division...
September 15, 2017: Annual Review of Genetics
https://www.readbyqxmd.com/read/28933593/dynein-promotes-porcine-oocyte-meiotic-progression-by-maintaining-cytoskeletal-structures-and-cortical-granule-arrangement
#2
Yilong Miao, Changyin Zhou, Zhaokang Cui, Liansheng Tang, Xiayan ShiYang, Yajuan Lu, Mianqun Zhang, Xiaoxin Dai, Bo Xiong
Cytoplasmic dynein is a family of cytoskeletal motor proteins that move towards the minus-end of the microtubules to perform functions in a variety of mitotic processes such as cargo transport, organelle positioning, chromosome movement and centrosome assembly. However, its specific roles during mammalian oocyte meiosis have not been fully defined. Herein, we investigated the critical events during porcine oocyte meiotic maturation after inhibition of dynein by Ciliobrevin D treatment. We found that oocyte meiotic progression was arrested when inhibited of dynein by showing the poor expansion of cumulus cells and decreased rate of polar body extrusion...
September 21, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28931596/non-random-%C3%AE-tuna-dependent-spatial-pattern-of-microtubule-nucleation-at-the-golgi
#3
Anna A W M Sanders, Kevin Chang, Xiaodong Zhu, Roslin J Thoppil, William R Holmes, Irina Kaverina
Non-centrosomal microtubule (MT) nucleation at the Golgi generates MT network asymmetry in motile vertebrate cells. Investigating Golgi-derived MT (GDMT) distribution, we find that MT asymmetry arises from non-random nucleation sites at the Golgi (hotspots). Using computational simulations, we propose two plausible mechanistic models of GDMT nucleation leading to this phenotype. In the "Cooperativity" model, formation of a single GDMT promotes further nucleation at the same site. In the "Heterogeneous Golgi" model, MT nucleation is dramatically upregulated at discrete and sparse locations within the Golgi...
September 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28931032/a-microtubule-based-minimal-model-for-spontaneous-and-persistent-spherical-cell-polarity
#4
Panayiotis Foteinopoulos, Bela M Mulder
We propose a minimal model for the spontaneous and persistent generation of polarity in a spherical cell based on dynamic microtubules and a single mobile molecular component. This component, dubbed the polarity factor, binds to microtubules nucleated from a centrosome located in the center of the cell, is subsequently delivered to the cell membrane, where it diffuses until it unbinds. The only feedback mechanism we impose is that the residence time of the microtubules at the membrane increases with the local density of the polarity factor...
2017: PloS One
https://www.readbyqxmd.com/read/28930533/53bp1-a-guardian-for-centrosomal-integrity
#5
Haeyoung Kim, Hyungshin Yim
53BP1 is known as a mediator in DNA damage response and a regulator of DNA double-stranded breaks (DSBs) repair. 53BP1 was recently reported to be a centrosomal protein and a binding partner of mitotic polo-like kinase 1 (Plk1). The stability of 53BP1, in response to DSBs, is regulated by its phosphorylation, deubiquitination, and ubiquitination. During mitosis, 53BP1 is stabilized by phosphorylation at S380, a putative binding region with polo-box domain of Plk1, and deubiquitination by ubiquitin-specific protease 7 (USP7)...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28928827/inhibition-of-c-myc-expression-accounts-for-an-increase-in-the-number-of-multinucleated-cells-in-human-cervical-epithelial-cells
#6
Feng Mei Cui, Xiu Jin Sun, Cheng Cheng Huang, Qiu Chen, Yong Ming He, Shi Meng Zhang, Hua Guan, Man Song, Ping Kun Zhou, Jun Hou
The present study aimed to explore the mechanisms by which c-Myc is involved in mitotic catastrophe. HeLa-630 is a cell line stably silenced for c-Myc expression that was established in the laboratory of the School of Radiation Medicine and Protection. Multinucleated cells were observed in this line, and gene expression analysis was utilized to examine differences in gene expression in these cells compared with in the control cells transfected with the control plasmid. Gene ontology analysis was performed for differentially expressed genes...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28923976/catch-and-release-14-3-3-controls-ncd-in-meiotic-spindles
#7
Mary Dasso
During Drosophila melanogaster oogenesis, spindle assembly occurs without centrosomes and relies on signals from chromosomes. Beaven et al. (2017. J. Cell. Biol. https://doi.org/10.1083/jcb.201704120) show that 14-3-3 proteins bind and inhibit a key microtubule motor, Ncd, during oogenesis, but Aurora B releases Ncd inhibition near chromosomes, allowing Ncd to work in the right time and place.
September 18, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28922450/structural-insight-into-the-xtacc3-xmap215-interaction-from-cd-and-nmr-studies-on-model-peptides
#8
Angélica Partida-Hanon, Miguel A Treviño, Miguel Mompeán, Ma Ángeles Jiménez, Marta Bruix
TACC3 is a centrosomal adaptor protein that plays important roles during mitotic spindle assembly. It interacts with chTOG/XMAP215, which catalyzes the addition of tubulin dimers during microtubule growth. A 3D coiled-coil model for this interaction is available but the structural details are not well described. To characterize this interaction at atomic resolution, we have designed a simplified version of the system based on small peptides. Four different peptides have been studied by circular dichroism and nuclear magnetic resonance both singly and in all possible combinations; namely, five peptide pairs and two trios...
September 18, 2017: Biopolymers
https://www.readbyqxmd.com/read/28920929/structural-investigation-of-nucleophosmin-interaction-with-the-tumor-suppressor-fbw7%C3%AE
#9
A Di Matteo, M Franceschini, A Paiardini, A Grottesi, S Chiarella, S Rocchio, C Di Natale, D Marasco, L Vitagliano, C Travaglini-Allocatelli, L Federici
Nucleophosmin (NPM1) is a multifunctional nucleolar protein implicated in ribogenesis, centrosome duplication, cell cycle control, regulation of DNA repair and apoptotic response to stress stimuli. The majority of these functions are played through the interactions with a variety of protein partners. NPM1 is frequently overexpressed in solid tumors of different histological origin. Furthermore NPM1 is the most frequently mutated protein in acute myeloid leukemia (AML) patients. Mutations map to the C-terminal domain and lead to the aberrant and stable localization of the protein in the cytoplasm of leukemic blasts...
September 18, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28918951/collective-force-regulation-in-anti-parallel-microtubule-gliding-by-dimeric-kif15-kinesin-motors
#10
Dana N Reinemann, Emma G Sturgill, Dibyendu Kumar Das, Miriam Steiner Degen, Zsuzsanna Vörös, Wonmuk Hwang, Ryoma Ohi, Matthew J Lang
During cell division, the mitotic kinesin-5 Eg5 generates most of the force required to separate centrosomes during spindle assembly. However, Kif15, another mitotic kinesin, can replace Eg5 function, permitting mammalian cells to acquire resistance to Eg5 poisons. Unlike Eg5, the mechanism by which Kif15 generates centrosome separation forces is unknown. Here we investigated the mechanical properties and force generation capacity of Kif15 at the single-molecule level using optical tweezers. We found that the non-motor microtubule-binding tail domain interacts with the microtubule's E-hook tail with a rupture force higher than the stall force of the motor...
September 8, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28916777/the-catalytic-subunit-of-dna-polymerase-%C3%AE-inhibits-%C3%AE-turc-activity-and-regulates-golgi-derived-microtubules
#11
Yuehong Shen, Pengfei Liu, Taolue Jiang, Yu Hu, Franco K C Au, Robert Z Qi
γ-Tubulin ring complexes (γTuRCs) initiate microtubule growth and mediate microtubule attachment at microtubule-organizing centers, such as centrosomes and the Golgi complex. However, the mechanisms that control γTuRC-mediated microtubule nucleation have remained mostly unknown. Here, we show that the DNA polymerase δ catalytic subunit (PolD1) binds directly to γTuRCs and potently inhibits γTuRC-mediated microtubule nucleation. Whereas PolD1 depletion through RNA interference does not influence centrosome-based microtubule growth, the depletion augments microtubule nucleation at the Golgi complex...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28915666/ard1-mediated-aurora-kinase-a-acetylation-promotes-cell-proliferation-and-migration
#12
Tam Thuy Lu Vo, Ji-Hyeon Park, Ji Hae Seo, Eun Ji Lee, Hoon Choi, Sung-Jin Bae, Hoang Le, Sunho An, Hye Shin Lee, Hee-Jun Wee, Kyu-Won Kim
Aurora kinase A (AuA) is a prerequisite for centrosome maturation, separation, and mitotic spindle assembly, thus, it is essential for cell cycle regulation. Overexpression of AuA is implicated in poor prognosis of many types of cancer. However, the regulatory mechanisms underlying the functions of AuA are still not fully understood. Here, we report that AuA colocalizes with arrest defective protein 1 (ARD1) acetyltransferase during cell division and cell migration. Additionally, AuA is acetylated by ARD1 at lysine residues at positions 75 and 125...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903390/association-between-the-functional-polymorphism-ile31phe-in-the-aurka-gene-and-susceptibility-of-hepatocellular-carcinoma-in-chronic-hepatitis-b-virus-carriers
#13
Zhiyu Bao, Lei Lu, Xinyi Liu, Bingqian Guo, Yun Zhai, Yuanfeng Li, Yahui Wang, Bobo Xie, Qian Ren, Pengbo Cao, Yuqing Han, Weihua Jia, Minshan Chen, Xinqiang Liang, Xuan Wang, Yi-Xin Zeng, Fuchu He, Hongxing Zhang, Ying Cui, Gangqiao Zhou
Aurora kinase A (AURKA) is a serine threonine kinase which affects chromosomal separation and mitotic spindle stability through interaction with the centrosome during mitosis. Two functional nonsynonymous polymorphisms of the AURKA gene (Ile31Phe and Val57Ile) have been reported recently. We analyzed the association between the two polymorphisms and risk of the occurrence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in the Guangxi population consisting of 348 patients with HCC and 359 control subjects, and then validated the significant association in the Guangdong population consisting of 440 cases and 456 controls...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28902444/genomewide-association-studies-of-suicide-attempts-in-us-soldiers
#14
Murray B Stein, Erin B Ware, Colter Mitchell, Chia-Yen Chen, Susan Borja, Tianxi Cai, Catherine L Dempsey, Carol S Fullerton, Joel Gelernter, Steven G Heeringa, Sonia Jain, Ronald C Kessler, James A Naifeh, Matthew K Nock, Stephan Ripke, Xiaoying Sun, Jean C Beckham, Nathan A Kimbrel, Robert J Ursano, Jordan W Smoller
Suicide is a global public health problem with particular resonance for the US military. Genetic risk factors for suicidality are of interest as indicators of susceptibility and potential targets for intervention. We utilized population-based nonclinical cohorts of US military personnel (discovery: N = 473 cases and N = 9778 control subjects; replication: N = 135 cases and N = 6879 control subjects) and a clinical case-control sample of recent suicide attempters (N = 51 cases and N = 112 control subjects) to conduct GWAS of suicide attempts (SA)...
September 13, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28900114/programmed-self-assembly-of-a-biochemical-and-magnetic-scaffold-to-trigger-and-manipulate-microtubule-structures
#15
Rémi Ducasse, Wei-An Wang, Marina Garcia-Jove Navarro, Nicolas Debons, Alexandra Colin, Jérémie Gautier, Jean-Michel Guigner, François Guyot, Zoher Gueroui
Artificial bio-based scaffolds offer broad applications in bioinspired chemistry, nanomedicine, and material science. One current challenge is to understand how the programmed self-assembly of biomolecules at the nanometre level can dictate the emergence of new functional properties at the mesoscopic scale. Here we report a general approach to design genetically encoded protein-based scaffolds with modular biochemical and magnetic functions. By combining chemically induced dimerization strategies and biomineralisation, we engineered ferritin nanocages to nucleate and manipulate microtubule structures upon magnetic actuation...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28900014/regulation-of-the-cell-cycle-and-centrosome-biology-by-deubiquitylases
#16
REVIEW
Sarah Darling, Andrew B Fielding, Dorota Sabat-Pośpiech, Ian A Prior, Judy M Coulson
Post-translational modification of proteins by ubiquitylation is increasingly recognised as a highly complex code that contributes to the regulation of diverse cellular processes. In humans, a family of almost 100 deubiquitylase enzymes (DUBs) are assigned to six subfamilies and many of these DUBs can remove ubiquitin from proteins to reverse signals. Roles for individual DUBs have been delineated within specific cellular processes, including many that are dysregulated in diseases, particularly cancer. As potentially druggable enzymes, disease-associated DUBs are of increasing interest as pharmaceutical targets...
September 12, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28898644/centrosome-biology-polymer-based-centrosome%C3%A2-maturation
#17
Gagan D Gupta, Laurence Pelletier
The molecular mechanisms that control how the centrosome increases in size and microtubule nucleation capacity during mitosis have remained elusive. Recent work using in vitro assays provide exciting clues as to how this may occur.
September 11, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28884397/brca1-gene-function-and-deficiency
#18
REVIEW
Miho Takaoka, Yoshio Miki
The BRCA1 protein, a hereditary breast and ovarian cancer-causing gene product, is known as a multifunctional protein that performs various functions in cells. It is well known, along with BRCA 2, to cause hereditary breast and ovarian cancer, but here we will specifically focus on BRCA1. We introduce the mechanism and the latest report on homologous recombination repair, replication, involvement in checkpoint regulation, transcription, chromatin remodeling, and cytoplasmic function (centrosome regulation, apoptosis, selective autophagy), and consider the possibility of carcinogenesis from inhibition of the intracellular functions in each...
September 7, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28881819/apio-ee-9-is-a-novel-aurora-a-and-b-antagonist-that-suppresses-esophageal-cancer-growth-in-a-pdx-mouse-model
#19
Guoguo Jin, Ke Yao, Zhiping Guo, Zhenjiang Zhao, Kangdong Liu, Fangfang Liu, Hanyong Chen, Dhilli Rao Gorja, Kanamata Reddy, Ann M Bode, Ziming Dong, Zigang Dong
Esophageal cancer (EC) is one of the most aggressive malignancies of the upper aerodigestive tract. Over the past three decades, with advances in surgical techniques and treatment, the prognosis of esophageal cancer has only slowly improved. Thus identifying novel molecular targets and developing therapeutic agents are critical. Aurora kinases play a crucial role in mitosis and selective inhibitors might provide an effective therapeutic treatment for cancer. However, the role of Aurora kinases in EC is still inadequately studied...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881785/mir-486-5p-negatively-regulates-oncogenic-nek2-in-hepatocellular-carcinoma
#20
Shun-Jun Fu, Jian Chen, Fei Ji, Wei-Qiang Ju, Qiang Zhao, Mao-Gen Chen, Zhi-Yong Guo, Lin-Wei Wu, Yi Ma, Dong-Ping Wang, Xiao-Feng Zhu, Xiao-Shun He
NEK2 is a member of the NIMA-related family of serine/threonine centrosomal kinases. We analyzed the relationship between differential expression of NEK2 and hepatocellular carcinoma (HCC) patient outcomes after liver transplants. We also studied the microRNAs that affect NEK2 expression. Analysis of multiple microarrays in the Oncomine database revealed that NEK2 expression was higher in HCC tissues than adjacent normal liver tissues. High NEK2 expression correlated with tumor size, pathological grade and macro- and microvascular invasion...
August 8, 2017: Oncotarget
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