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https://www.readbyqxmd.com/read/28107777/the-dc1-domain-protein-vacuoleless-gametophytes-is-essential-for-female-and-male-gametophyte-development-in-arabidopsis
#1
Sebastián D'Ippólito, Leonardo Agustín Arias, Claudia Anahí Casalongué, Gabriela Carolina Pagnussat, Diego Fernando Fiol
In this work we identified VACUOLELESS GAMETOPHYTES (VLG) as a DC1 domain containing protein present in the endomembrane system essential for both female and male gametophyte development. VLG was originally annotated as a gene coding for an unknown function protein containing DC1 domains. DC1 domains are cysteine and histidine -rich zinc finger domains found exclusively in the plant Kingdom that have been named based on its similarity with the C1 domain present in protein kinase C (PKC). In Arabidopsis, both male and female gametophytes are characterized by the formation of a big vacuole early in development, which is absent in vlg mutant plants...
January 20, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28105216/identification-of-potential-therapeutic-targets-for-colorectal-cancer-by-bioinformatics-analysis
#2
Ming Yan, Maomin Song, Rixing Bai, Shi Cheng, Wenmao Yan
The aim of the present study was to identify potential therapeutic targets for colorectal cancer (CRC). The gene expression profile GSE32323, containing 34 samples, including 17 specimens of CRC tissues and 17 of paired normal tissues from CRC patients, was downloaded from the Gene Expression Omnibus database. Following data preprocessing using the Affy and preprocessCore packages, the differentially-expressed genes (DEGs) between the two types of samples were identified with the Linear Models for Microarray Analysis package...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28100785/protein-kinase-c-controls-binding-of-igo-ensa-proteins-to-protein-phosphatase-2a-in-budding-yeast
#3
Vu Thai, Noah Dephoure, Amit Weiss, Jacqueline Ferguson, Ricardo Leitao, Steven P Gygi, Douglas R Kellogg
Protein phosphatase 2A (PP2A) plays important roles in controlling mitosis in all eukaryotic cells. The form of PP2A that controls mitosis is associated with a conserved regulatory subunit that is called B55 in vertebrates and Cdc55 in budding yeast. The activity of this form of PP2A can be inhibited by binding of conserved Igo/ENSA proteins. Although the mechanisms that activate Igo/ENSA to bind to PP2A are well understood, little is known about how they are inactivated. Here, we have analyzed regulation of Igo/ENSA in the context of a checkpoint pathway that links mitotic entry to membrane growth in budding yeast...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28096334/role-of-cct-chaperonin-in-the-disassembly-of-mitotic-checkpoint-complexes
#4
Sharon Kaisari, Danielle Sitry-Shevah, Shirly Miniowitz-Shemtov, Adar Teichner, Avram Hershko
The mitotic checkpoint system prevents premature separation of sister chromatids in mitosis and thus ensures the fidelity of chromosome segregation. When this checkpoint is active, a mitotic checkpoint complex (MCC), composed of the checkpoint proteins Mad2, BubR1, Bub3, and Cdc20, is assembled. MCC inhibits the ubiquitin ligase anaphase promoting complex/cyclosome (APC/C), whose action is necessary for anaphase initiation. When the checkpoint signal is turned off, MCC is disassembled, a process required for exit from checkpoint-arrested state...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28079003/colorectal-cancer-chemotherapy-the-evolution-of-treatment-and-new-approaches
#5
Rachel M McQuade, Vanesa Stojanovska, Joel C Bornstein, Kulmira Nurgali
Colorectal cancer (CRC) is one the greatest contributors to cancer related mortality. Although 5 year survival rate for patients at the early stage of CRC (stages I and II) is above 60%, more than 50% of patients are diagnosed at or beyond stage III when distant metastasis has already occurred, in which case 5 year survival rate drops to 10%. Chemotherapeutic intervention coupled with surgery is the backbone of metastatic CRC treatment and the only means of enhanced survival. For decades following its discovery, an antimetabolite 5-fluorouracil (5-FU) was the only chemotherapeutic agent available to successfully improve 12 month survival in CRC patients...
January 11, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28074435/plk1-inhibition-leads-to-a-failure-of-mitotic-division-during-the-first-mitotic-division-in-pig-embryos
#6
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/28072818/glucose-abl1-tor-signaling-modulates-cell-cycle-tuning-to-control-terminal-appressorial-cell-differentiation
#7
Margarita Marroquin-Guzman, Guangchao Sun, Richard A Wilson
The conserved target of rapamycin (TOR) pathway integrates growth and development with available nutrients, but how cellular glucose controls TOR function and signaling is poorly understood. Here, we provide functional evidence from the devastating rice blast fungus Magnaporthe oryzae that glucose can mediate TOR activity via the product of a novel carbon-responsive gene, ABL1, in order to tune cell cycle progression during infection-related development. Under nutrient-free conditions, wild type (WT) M. oryzae strains form terminal plant-infecting cells (appressoria) at the tips of germ tubes emerging from three-celled spores (conidia)...
January 10, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28067305/gomisin-n-inhibits-adipogenesis-and-prevents-high-fat-diet-induced-obesity
#8
Min-Kyung Jang, Ye-Rang Yun, Ji-Hyun Kim, Mi-Hee Park, Myeong Ho Jung
Gomisin N (GN) is a physiological lignan derived from Schisandra chinensis. In the present study, we investigated the inhibitory effects of GN on differentiation of 3T3-L1 preadipocytes and the anti-obesity effects of GN in high-fat diet (HFD)-induced obese mice. Incubation with GN significantly inhibited the differentiation of 3T3-L1 preadipocytes in a dose-dependent manner. This inhibitory effect primarily occurred at an early adipogenic stage through impairment of mitotic clonal expansion (MCE) caused by cell cycle arrest at the G1/S phase transition...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28064118/pb-low-doses-induced-genotoxicity-in-lactuca-sativa-plants
#9
S Silva, P Silva, H Oliveira, I Gaivão, M Matos, O Pinto-Carnide, C Santos
Soil and water contamination by lead (Pb) remains a topic of great concern, particularly regarding crop production. The admissible Pb values in irrigation water in several countries range from ≈0.1 to ≈5 mg L(-1). In order to evaluate putative effects of Pb within legal doses on crops growth, we exposed Lactuca sativa seeds and seedlings to increasing doses of Pb(NO3)2 up to 20 mg L(-1). The OECD parameter seed germination and seedling/plant growth were not affected by any of the Pb-concentrations used...
December 27, 2016: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28055975/mitotic-catastrophe-and-cell-cycle-arrest-are-alternative-cell-death-pathways-executed-by-bortezomib-in-rituximab-resistant-b-cell-lymphoma-cells
#10
Juan J Gu, Gregory P Kaufman, Cory Mavis, Myron S Czuczman, Francisco J Hernandez-Ilizaliturri
The ubiqutin-proteasome system (UPS) plays a role in rituximab-chemotherapy resistance and bortezomib (BTZ) possesses caspase-dependent (i.e. Bak stabilization) and a less characterized caspase-independent mechanism-of-action(s). Here, we define BTZ-induced caspase-independent cell death pathways. A panel of rituximab-sensitive (RSCL), rituximab-resistant cell lines (RRCL) and primary tumor cells derived from lymphoma patients (N = 13) were exposed to BTZ. Changes in cell viability, cell-cycle, senescence, and mitotic index were quantified...
December 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/28045256/n-heterocyclic-4-phenylpiperazin-1-yl-methanones-derived-from-phenoxazine-and-phenothiazine-as-highly-potent-inhibitors-of-tubulin-polymerization
#11
Helge Prinz, Ann-Kathrin Ridder, Kirsten Vogel, Konrad J Böhm, Igor Ivanov, Jahan B Ghasemi, Elham Aghaee, Klaus Müller
We report here a series of 27 10-(4-phenylpiperazin-1-yl)methanones derived from tricyclic heterocycles which were screened for effects on tumor cell growth, inhibition of tubulin polymerization, and induction of cell cycle arrest. Several analogues, among them the 10-(4-(3-methoxyphenyl)piperazine-1-carbonyl)-10H-phenoxazine-3-carbonitrile (16o), showed excellent antiproliferative properties, with low nanomolar GI50 values (16o, mean GI50 of 3.3 nM) against a large number (93) of cancer cell lines. Fifteen compounds potently inhibited tubulin polymerization...
January 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28040797/disease-subtype-independent-biomarkers-of-breast-cancer-chemoprevention-by-the-ayurvedic-medicine-phytochemical-withaferin-a
#12
Suman K Samanta, Anuradha Sehrawat, Su-Hyeong Kim, Eun-Ryeong Hahm, Yongli Shuai, Ruchi Roy, Subrata K Pore, Krishna B Singh, Susan M Christner, Jan H Beumer, Nancy E Davidson, Shivendra V Singh
BACKGROUND: A nontoxic chemopreventive intervention efficacious against different subtypes of breast cancer is still a clinically unmet need. The present study was undertaken to determine the efficacy of an Ayurvedic medicine phytochemical (Withaferin A, [WA]) for chemoprevention of breast cancer and to elucidate its mode of action. METHODS: Chemopreventive efficacy of WA (4 and 8 mg/kg body weight) was determined using a rat model of breast cancer induced by N-methyl-N-nitrosourea (MNU; n = 14 for control group, n = 15 for 4 mg/kg group, and n = 18 for 8 mg/kg group)...
June 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28034647/synthesis-and-biological-evaluation-of-cis-restricted-triazole-tetrazole-mimics-of-combretastatin-benzothiazole-hybrids-as-tubulin-polymerization-inhibitors-and-apoptosis-inducers
#13
A V Subba Rao, Konderu Swapna, Siddiq Pasha Shaik, V Lakshma Nayak, T Srinivasa Reddy, Satish Sunkari, Thokhir Basha Shaik, Chandrakant Bagul, Ahmed Kamal
A series of colchicine site binding tubulin inhibitors were synthesized by the modification of the combretastatin pharmacophore. The ring B was replaced by the pharmacologically relevant benzothiazole scaffolds, and the cis configuration of the olefinic bond was restricted by the incorporation of a triazole and tetrazole rings which is envisaged by the structural resemblance to a tubulin inhibitor like combretastatin (CA-4). These compounds were evaluated for their antiproliferative activity on selected cancer cell lines and an insight in the structure activity relationship was developed...
December 9, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28030839/antagonizing-functions-of-bard1-and-its-alternatively-spliced-variant-bard1%C3%AE-in-telomere-stability
#14
Maxim Pilyugin, Pierre-Alain André, Magdalena Ratajska, Alina Kuzniacka, Janusz Limon, Benjamin B Tournier, Julien Colas, Geoff Laurent, Irmgard Irminger-Finger
Previous reports have shown that expression of BARD1δ, a deletion-bearing isoform of BARD1, correlates with tumor aggressiveness and progression. We show that expression of BARD1δ induces cell cycle arrest in vitro and in vivo in non-malignant cells. We investigated the mechanism that leads to proliferation arrest and found that BARD1δ overexpression induced mitotic arrest with chromosome and telomere aberrations in cell cultures, in transgenic mice, and in cells from human breast and ovarian cancer patients with BARD1 mutations...
December 21, 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
#15
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...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/28017898/oxidative-stress-induces-mitotic-arrest-by-inhibiting-aurora-a-involved-mitotic-spindle-formation
#16
Guang-Fei Wang, Qincai Dong, Yuanyuan Bai, Jing Yuan, Quanbin Xu, Cheng Cao, Xuan Liu
Oxidative stress contributes to the oxidative modification of cellular components, including lipids, proteins and DNA, and results in DNA damage, cell cycle arrest, cellular dysfunction and apoptosis. However, the mechanism underlying oxidative stress-induced mitotic abnormalities is not fully understood. In this study, we demonstrated that exogenous and endogenous reactive oxygen species (ROS) promoted mitotic arrest. Delayed formation and abnormal function of the mitotic spindle, which directly impeded mitosis and promoted abnormal chromosome separation, was responsible for ROS-induced mitotic arrest...
December 23, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28017606/generation-of-a-spindle-checkpoint-arrest-from-synthetic-signaling-assemblies
#17
Ivan Yuan, Ioanna Leontiou, Priya Amin, Karen M May, Sadhbh Soper Ní Chafraidh, Eliška Zlámalová, Kevin G Hardwick
The spindle checkpoint acts as a mitotic surveillance system, monitoring interactions between kinetochores and spindle microtubules and ensuring high-fidelity chromosome segregation [1-3]. The checkpoint is activated by unattached kinetochores, and Mps1 kinase phosphorylates KNL1 on conserved MELT motifs to generate a binding site for the Bub3-Bub1 complex [4-7]. This leads to dynamic kinetochore recruitment of Mad proteins [8, 9], a conformational change in Mad2 [10-12], and formation of the mitotic checkpoint complex (MCC: Cdc20-Mad3-Mad2 [13-15])...
January 9, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28012437/autophagy-deficient-keratinocytes-display-increased-dna-damage-senescence-and-aberrant-lipid-composition-after-oxidative-stress-in-vitro-and-in-vivo
#18
Xiuzu Song, Marie Sophie Narzt, Ionela Mariana Nagelreiter, Philipp Hohensinner, Lucia Terlecki-Zaniewicz, Erwin Tschachler, Johannes Grillari, Florian Gruber
Autophagy allows cells fundamental adaptations to metabolic needs and to stress. Using autophagic bulk degradation cells can clear crosslinked macromolecules and damaged organelles that arise under redox stress. Accumulation of such debris results in cellular dysfunction and is observed in aged tissue and senescent cells. Conversely, promising anti-aging strategies aim at inhibiting the mTOR pathway and thereby activating autophagy, to counteract aging associated damage. We have inactivated autophagy related 7 (Atg7), an essential autophagy gene, in murine keratinocytes (KC) and have found in an earlier study that this resulted in increased baseline oxidative stress and reduced capacity to degrade crosslinked proteins after oxidative ultraviolet stress...
December 18, 2016: Redox Biology
https://www.readbyqxmd.com/read/27993567/cell-cycle-dependent-changes-in-the-plasma-membrane-organization-of-mammalian-cells
#19
Manuela Denz, Salvatore Chiantia, Andreas Herrmann, Peter Mueller, Thomas Korte, Roland Schwarzer
Lipid membranes are major structural elements of all eukaryotic and prokaryotic organisms. Although many aspects of their biology have been studied extensively, their dynamics and lateral heterogeneity are still not fully understood. Recently, we observed a cell-to-cell variability in the plasma membrane organization of CHO-K1 cells (Schwarzer et al., 2014). We surmised that cell cycle dependent changes of the individual cells from our unsynchronized cell population account for this phenomenon. In the present study, this hypothesis was tested...
December 18, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27989101/overcomes-imatinib-resistance-by-depleting-bcr-abl-in-chronic-myeloid-leukemia
#20
Xiaoyan Sun, Xueting Cai, Jie Yang, Jiao Chen, Caixia Guo, Peng Cao
Cantharidin (CTD) is an active compound isolated from the traditional Chinese medicine blister beetle and displayed anticancer properties against various types of cancer cells. However, little is known about its effect on human chronic myeloid leukemia (CML) cells, including imatinib-resistant CML cells. The objective of this study was to investigate whether CTD could overcome imatinib resistance in imatinib-resistant CML cells and to explore the possible underlying mechanisms associated with the effect. Our results showed that CTD strongly inhibited the growth of both imatinib-sensitive and imatinib-resistant CML cells...
December 2016: Molecules and Cells
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