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  • Models, Biological  (13)
  • Nature Publishing Group (NPG)  (13)
  • American Chemical Society
  • National Academy of Sciences
  • 2010-2014  (13)
  • 2011  (13)
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  • 2010-2014  (13)
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  • 1
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    SMAD4-dependent barrier constrains prostate cancer growth and metastatic progression (2011)
    Nature Publishing Group (NPG)
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    Publication Date: 2011-02-04
    Description: Effective clinical management of prostate cancer (PCA) has been challenged by significant intratumoural heterogeneity on the genomic and pathological levels and limited understanding of the genetic elements governing disease progression. Here, we exploited the experimental merits of the mouse to test the hypothesis that pathways constraining progression might be activated in indolent Pten-null mouse prostate tumours and that inactivation of such progression barriers in mice would engender a metastasis-prone condition. Comparative transcriptomic and canonical pathway analyses, followed by biochemical confirmation, of normal prostate epithelium versus poorly progressive Pten-null prostate cancers revealed robust activation of the TGFbeta/BMP-SMAD4 signalling axis. The functional relevance of SMAD4 was further supported by emergence of invasive, metastatic and lethal prostate cancers with 100% penetrance upon genetic deletion of Smad4 in the Pten-null mouse prostate. Pathological and molecular analysis as well as transcriptomic knowledge-based pathway profiling of emerging tumours identified cell proliferation and invasion as two cardinal tumour biological features in the metastatic Smad4/Pten-null PCA model. Follow-on pathological and functional assessment confirmed cyclin D1 and SPP1 as key mediators of these biological processes, which together with PTEN and SMAD4, form a four-gene signature that is prognostic of prostate-specific antigen (PSA) biochemical recurrence and lethal metastasis in human PCA. This model-informed progression analysis, together with genetic, functional and translational studies, establishes SMAD4 as a key regulator of PCA progression in mice and humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753179/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753179/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ding, Zhihu -- Wu, Chang-Jiun -- Chu, Gerald C -- Xiao, Yonghong -- Ho, Dennis -- Zhang, Jingfang -- Perry, Samuel R -- Labrot, Emma S -- Wu, Xiaoqiu -- Lis, Rosina -- Hoshida, Yujin -- Hiller, David -- Hu, Baoli -- Jiang, Shan -- Zheng, Hongwu -- Stegh, Alexander H -- Scott, Kenneth L -- Signoretti, Sabina -- Bardeesy, Nabeel -- Wang, Y Alan -- Hill, David E -- Golub, Todd R -- Stampfer, Meir J -- Wong, Wing H -- Loda, Massimo -- Mucci, Lorelei -- Chin, Lynda -- DePinho, Ronald A -- P50 CA090381/CA/NCI NIH HHS/ -- P50 CA090381-08/CA/NCI NIH HHS/ -- P50 CA90381/CA/NCI NIH HHS/ -- R01 5R01CA136578/CA/NCI NIH HHS/ -- R01 CA131945/CA/NCI NIH HHS/ -- R01CA131945/CA/NCI NIH HHS/ -- R01CA141298/CA/NCI NIH HHS/ -- U01-CA84313/CA/NCI NIH HHS/ -- England -- Nature. 2011 Feb 10;470(7333):269-73. doi: 10.1038/nature09677. Epub 2011 Feb 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21289624" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Morphogenetic Proteins/metabolism ; Cell Proliferation ; Cyclin D1/genetics/metabolism ; *Disease Progression ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor/physiology ; Humans ; Lung Neoplasms/secondary ; Lymphatic Metastasis ; Male ; Mice ; Mice, Transgenic ; Models, Biological ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Metastasis/genetics/*pathology ; Osteopontin/genetics/metabolism ; PTEN Phosphohydrolase/deficiency/genetics ; Penetrance ; Prognosis ; Prostate/metabolism ; Prostate-Specific Antigen/metabolism ; Prostatic Neoplasms/diagnosis/genetics/*pathology ; Smad4 Protein/deficiency/genetics/*metabolism ; Transforming Growth Factor beta
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
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    Modelling schizophrenia using human induced pluripotent stem cells (2011)
    Nature Publishing Group (NPG)
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    Publication Date: 2011-04-15
    Description: Schizophrenia (SCZD) is a debilitating neurological disorder with a world-wide prevalence of 1%; there is a strong genetic component, with an estimated heritability of 80-85%. Although post-mortem studies have revealed reduced brain volume, cell size, spine density and abnormal neural distribution in the prefrontal cortex and hippocampus of SCZD brain tissue and neuropharmacological studies have implicated dopaminergic, glutamatergic and GABAergic activity in SCZD, the cell types affected in SCZD and the molecular mechanisms underlying the disease state remain unclear. To elucidate the cellular and molecular defects of SCZD, we directly reprogrammed fibroblasts from SCZD patients into human induced pluripotent stem cells (hiPSCs) and subsequently differentiated these disorder-specific hiPSCs into neurons (Supplementary Fig. 1). SCZD hiPSC neurons showed diminished neuronal connectivity in conjunction with decreased neurite number, PSD95-protein levels and glutamate receptor expression. Gene expression profiles of SCZD hiPSC neurons identified altered expression of many components of the cyclic AMP and WNT signalling pathways. Key cellular and molecular elements of the SCZD phenotype were ameliorated following treatment of SCZD hiPSC neurons with the antipsychotic loxapine. To date, hiPSC neuronal pathology has only been demonstrated in diseases characterized by both the loss of function of a single gene product and rapid disease progression in early childhood. We now report hiPSC neuronal phenotypes and gene expression changes associated with SCZD, a complex genetic psychiatric disorder.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392969/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392969/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brennand, Kristen J -- Simone, Anthony -- Jou, Jessica -- Gelboin-Burkhart, Chelsea -- Tran, Ngoc -- Sangar, Sarah -- Li, Yan -- Mu, Yangling -- Chen, Gong -- Yu, Diana -- McCarthy, Shane -- Sebat, Jonathan -- Gage, Fred H -- P01 NS028121/NS/NINDS NIH HHS/ -- P30 NS072031/NS/NINDS NIH HHS/ -- R01 MH083911/MH/NIMH NIH HHS/ -- England -- Nature. 2011 May 12;473(7346):221-5. doi: 10.1038/nature09915. Epub 2011 Apr 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Salk Institute for Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21490598" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Antipsychotic Agents/pharmacology ; Cell Differentiation ; Cells, Cultured ; Cellular Reprogramming/genetics ; Child ; Female ; Fibroblasts/cytology ; Gene Expression Profiling ; *Gene Expression Regulation/drug effects ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Loxapine/pharmacology ; Male ; Membrane Proteins/metabolism ; Models, Biological ; Neurites ; Neurons/*cytology/drug effects/*metabolism ; Phenotype ; Pluripotent Stem Cells/*cytology/*metabolism/pathology ; Receptors, Glutamate/metabolism ; Schizophrenia/*pathology ; Young Adult
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
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    Structure and function of a membrane component SecDF that enhances protein export (2011)
    Nature Publishing Group (NPG)
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    Publication Date: 2011-05-13
    Description: Protein translocation across the bacterial membrane, mediated by the secretory translocon SecYEG and the SecA ATPase, is enhanced by proton motive force and membrane-integrated SecDF, which associates with SecYEG. The role of SecDF has remained unclear, although it is proposed to function in later stages of translocation as well as in membrane protein biogenesis. Here, we determined the crystal structure of Thermus thermophilus SecDF at 3.3 A resolution, revealing a pseudo-symmetrical, 12-helix transmembrane domain belonging to the RND superfamily and two major periplasmic domains, P1 and P4. Higher-resolution analysis of the periplasmic domains suggested that P1, which binds an unfolded protein, undergoes functionally important conformational changes. In vitro analyses identified an ATP-independent step of protein translocation that requires both SecDF and proton motive force. Electrophysiological analyses revealed that SecDF conducts protons in a manner dependent on pH and the presence of an unfolded protein, with conserved Asp and Arg residues at the transmembrane interface between SecD and SecF playing essential roles in the movements of protons and preproteins. Therefore, we propose that SecDF functions as a membrane-integrated chaperone, powered by proton motive force, to achieve ATP-independent protein translocation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3697915/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3697915/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tsukazaki, Tomoya -- Mori, Hiroyuki -- Echizen, Yuka -- Ishitani, Ryuichiro -- Fukai, Shuya -- Tanaka, Takeshi -- Perederina, Anna -- Vassylyev, Dmitry G -- Kohno, Toshiyuki -- Maturana, Andres D -- Ito, Koreaki -- Nureki, Osamu -- R01 GM074840/GM/NIGMS NIH HHS/ -- England -- Nature. 2011 May 11;474(7350):235-8. doi: 10.1038/nature09980.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21562494" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Arginine/metabolism ; Asparagine/metabolism ; Bacterial Proteins/*chemistry/*metabolism ; Crystallography, X-Ray ; Hydrogen-Ion Concentration ; Membrane Proteins/*chemistry/*metabolism ; Membrane Transport Proteins/*chemistry/*metabolism ; Models, Biological ; Models, Molecular ; Nuclear Magnetic Resonance, Biomolecular ; Periplasm/chemistry/metabolism ; Protein Structure, Tertiary ; Protein Transport ; Protein Unfolding ; Proton-Motive Force ; Static Electricity ; Structure-Activity Relationship ; Thermus thermophilus/*chemistry/cytology
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
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    Polar actomyosin contractility destabilizes the position of the cytokinetic furrow (2011)
    Nature Publishing Group (NPG)
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    Publication Date: 2011-08-09
    Description: Cytokinesis, the physical separation of daughter cells at the end of mitosis, requires precise regulation of the mechanical properties of the cell periphery. Although studies of cytokinetic mechanics mostly focus on the equatorial constriction ring, a contractile actomyosin cortex is also present at the poles of dividing cells. Whether polar forces influence cytokinetic cell shape and furrow positioning remains an open question. Here we demonstrate that the polar cortex makes cytokinesis inherently unstable. We show that limited asymmetric polar contractions occur during cytokinesis, and that perturbing the polar cortex leads to cell shape oscillations, resulting in furrow displacement and aneuploidy. A theoretical model based on a competition between cortex turnover and contraction dynamics accurately accounts for the oscillations. We further propose that membrane blebs, which commonly form at the poles of dividing cells and whose role in cytokinesis has long been enigmatic, stabilize cell shape by acting as valves releasing cortical contractility. Our findings reveal an inherent instability in the shape of the dividing cell and unveil a novel, spindle-independent mechanism ensuring the stability of cleavage furrow positioning.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sedzinski, Jakub -- Biro, Mate -- Oswald, Annelie -- Tinevez, Jean-Yves -- Salbreux, Guillaume -- Paluch, Ewa -- England -- Nature. 2011 Aug 7;476(7361):462-6. doi: 10.1038/nature10286.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21822289" target="_blank"〉PubMed〈/a〉
    Keywords: Actomyosin/*metabolism ; Amides/pharmacology ; Aneuploidy ; Cell Line ; Cell Shape/drug effects/*physiology ; Cell Size/drug effects ; Cytokinesis/drug effects/*physiology ; HeLa Cells ; Humans ; Models, Biological ; Pyridines/pharmacology
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  • 5
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    Structure and mechanism of the uracil transporter UraA (2011)
    Nature Publishing Group (NPG)
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    Publication Date: 2011-03-23
    Description: The nucleobase/ascorbate transporter (NAT) proteins, also known as nucleobase/cation symporter 2 (NCS2) proteins, are responsible for the uptake of nucleobases in all kingdoms of life and for the transport of vitamin C in mammals. Despite functional characterization of the NAT family members in bacteria, fungi and mammals, detailed structural information remains unavailable. Here we report the crystal structure of a representative NAT protein, the Escherichia coli uracil/H(+) symporter UraA, in complex with uracil at a resolution of 2.8 A. UraA has a novel structural fold, with 14 transmembrane segments (TMs) divided into two inverted repeats. A pair of antiparallel beta-strands is located between TM3 and TM10 and has an important role in structural organization and substrate recognition. The structure is spatially arranged into a core domain and a gate domain. Uracil, located at the interface between the two domains, is coordinated mainly by residues from the core domain. Structural analysis suggests that alternating access of the substrate may be achieved through conformational changes of the gate domain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lu, Feiran -- Li, Shuo -- Jiang, Yang -- Jiang, Jing -- Fan, He -- Lu, Guifeng -- Deng, Dong -- Dang, Shangyu -- Zhang, Xu -- Wang, Jiawei -- Yan, Nieng -- England -- Nature. 2011 Apr 14;472(7342):243-6. doi: 10.1038/nature09885. Epub 2011 Mar 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Bio-membrane and Membrane Biotechnology, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21423164" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Transport ; Crystallography, X-Ray ; Escherichia coli/*chemistry ; Escherichia coli Proteins/*chemistry/*metabolism ; Hydrogen Bonding ; Membrane Transport Proteins/*chemistry/*metabolism ; Models, Biological ; Models, Molecular ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protons ; Structure-Activity Relationship ; Uracil/chemistry/*metabolism
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  • 6
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    Metabolic priming by a secreted fungal effector (2011)
    Nature Publishing Group (NPG)
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    Publication Date: 2011-10-07
    Description: Maize smut caused by the fungus Ustilago maydis is a widespread disease characterized by the development of large plant tumours. U. maydis is a biotrophic pathogen that requires living plant tissue for its development and establishes an intimate interaction zone between fungal hyphae and the plant plasma membrane. U. maydis actively suppresses plant defence responses by secreted protein effectors. Its effector repertoire comprises at least 386 genes mostly encoding proteins of unknown function and expressed exclusively during the biotrophic stage. The U. maydis secretome also contains about 150 proteins with probable roles in fungal nutrition, fungal cell wall modification and host penetration as well as proteins unlikely to act in the fungal-host interface like a chorismate mutase. Chorismate mutases are key enzymes of the shikimate pathway and catalyse the conversion of chorismate to prephenate, the precursor for tyrosine and phenylalanine synthesis. Root-knot nematodes inject a secreted chorismate mutase into plant cells likely to affect development. Here we show that the chorismate mutase Cmu1 secreted by U. maydis is a virulence factor. The enzyme is taken up by plant cells, can spread to neighbouring cells and changes the metabolic status of these cells through metabolic priming. Secreted chorismate mutases are found in many plant-associated microbes and might serve as general tools for host manipulation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Djamei, Armin -- Schipper, Kerstin -- Rabe, Franziska -- Ghosh, Anupama -- Vincon, Volker -- Kahnt, Jorg -- Osorio, Sonia -- Tohge, Takayuki -- Fernie, Alisdair R -- Feussner, Ivo -- Feussner, Kirstin -- Meinicke, Peter -- Stierhof, York-Dieter -- Schwarz, Heinz -- Macek, Boris -- Mann, Matthias -- Kahmann, Regine -- England -- Nature. 2011 Oct 5;478(7369):395-8. doi: 10.1038/nature10454.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute for Terrestrial Microbiology, Karl-von-Frisch-Strasse 10, D-35043 Marburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21976020" target="_blank"〉PubMed〈/a〉
    Keywords: Chorismate Mutase/*metabolism ; Cytoplasm/enzymology ; Gene Expression Regulation, Plant ; Genetic Complementation Test ; Host-Pathogen Interactions ; Metabolome ; Models, Biological ; Plant Proteins/metabolism ; Plastids/enzymology ; Protein Multimerization ; Saccharomyces cerevisiae/genetics ; Salicylic Acid/metabolism ; Two-Hybrid System Techniques ; Ustilago/*enzymology/*pathogenicity ; Virulence Factors/genetics/*metabolism ; Zea mays/*metabolism/*microbiology
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  • 7
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    Hydrostatic pressure and the actomyosin cortex drive mitotic cell rounding (2011)
    Nature Publishing Group (NPG)
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    Publication Date: 2011-01-05
    Description: During mitosis, adherent animal cells undergo a drastic shape change, from essentially flat to round. Mitotic cell rounding is thought to facilitate organization within the mitotic cell and be necessary for the geometric requirements of division. However, the forces that drive this shape change remain poorly understood in the presence of external impediments, such as a tissue environment. Here we use cantilevers to track cell rounding force and volume. We show that cells have an outward rounding force, which increases as cells enter mitosis. We find that this mitotic rounding force depends both on the actomyosin cytoskeleton and the cells' ability to regulate osmolarity. The rounding force itself is generated by an osmotic pressure. However, the actomyosin cortex is required to maintain this rounding force against external impediments. Instantaneous disruption of the actomyosin cortex leads to volume increase, and stimulation of actomyosin contraction leads to volume decrease. These results show that in cells, osmotic pressure is balanced by inwardly directed actomyosin cortex contraction. Thus, by locally modulating actomyosin-cortex-dependent surface tension and globally regulating osmotic pressure, cells can control their volume, shape and mechanical properties.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stewart, Martin P -- Helenius, Jonne -- Toyoda, Yusuke -- Ramanathan, Subramanian P -- Muller, Daniel J -- Hyman, Anthony A -- England -- Nature. 2011 Jan 13;469(7329):226-30. doi: 10.1038/nature09642. Epub 2011 Jan 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉ETH Zurich, Department of Biosystems Science and Engineering, CH-4058 Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21196934" target="_blank"〉PubMed〈/a〉
    Keywords: Actomyosin/*metabolism ; Animals ; Cell Shape/drug effects/*physiology ; Cell Size/drug effects ; Cytochalasin D/pharmacology ; Cytoskeleton/drug effects/*metabolism ; HeLa Cells ; Humans ; Hydrostatic Pressure ; Microscopy, Atomic Force ; *Mitosis ; Models, Biological ; Osmolar Concentration ; Osmotic Pressure ; Prophase
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    HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase (2011)
    Nature Publishing Group (NPG)
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    Publication Date: 2011-11-08
    Description: SAMHD1, an analogue of the murine interferon (IFN)-gamma-induced gene Mg11 (ref. 1), has recently been identified as a human immunodeficiency virus-1 (HIV-1) restriction factor that blocks early-stage virus replication in dendritic and other myeloid cells and is the target of the lentiviral protein Vpx, which can relieve HIV-1 restriction. SAMHD1 is also associated with Aicardi-Goutieres syndrome (AGS), an inflammatory encephalopathy characterized by chronic cerebrospinal fluid lymphocytosis and elevated levels of the antiviral cytokine IFN-alpha. The pathology associated with AGS resembles congenital viral infection, such as transplacentally acquired HIV. Here we show that human SAMHD1 is a potent dGTP-stimulated triphosphohydrolase that converts deoxynucleoside triphosphates to the constituent deoxynucleoside and inorganic triphosphate. The crystal structure of the catalytic core of SAMHD1 reveals that the protein is dimeric and indicates a molecular basis for dGTP stimulation of catalytic activity against dNTPs. We propose that SAMHD1, which is highly expressed in dendritic cells, restricts HIV-1 replication by hydrolysing the majority of cellular dNTPs, thus inhibiting reverse transcription and viral complementary DNA (cDNA) synthesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goldstone, David C -- Ennis-Adeniran, Valerie -- Hedden, Joseph J -- Groom, Harriet C T -- Rice, Gillian I -- Christodoulou, Evangelos -- Walker, Philip A -- Kelly, Geoff -- Haire, Lesley F -- Yap, Melvyn W -- de Carvalho, Luiz Pedro S -- Stoye, Jonathan P -- Crow, Yanick J -- Taylor, Ian A -- Webb, Michelle -- MC_U117512710/Medical Research Council/United Kingdom -- MC_U117533887/Medical Research Council/United Kingdom -- MC_U117565647/Medical Research Council/United Kingdom -- MC_UP_A253_1111/Medical Research Council/United Kingdom -- U117512710/Medical Research Council/United Kingdom -- U117565647/Medical Research Council/United Kingdom -- England -- Nature. 2011 Nov 6;480(7377):379-82. doi: 10.1038/nature10623.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Structure, MRC National Institute for Medical Research, London NW7 1AA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22056990" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Biocatalysis ; Catalytic Domain ; Crystallography, X-Ray ; Dendritic Cells/metabolism/virology ; Deoxyadenine Nucleotides/metabolism ; Deoxycytosine Nucleotides/metabolism ; Deoxyguanine Nucleotides/metabolism ; HIV-1/*physiology ; Humans ; Hydrolysis ; Models, Biological ; Models, Molecular ; Monomeric GTP-Binding Proteins/*chemistry/genetics/*metabolism ; Myeloid Cells/virology ; Nucleoside-Triphosphatase/*chemistry/genetics/*metabolism ; Protein Structure, Tertiary ; Reverse Transcription ; Thymine Nucleotides/metabolism ; Viral Regulatory and Accessory Proteins/metabolism ; Virus Replication
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    Intrinsic transition of embryonic stem-cell differentiation into neural progenitors (2011)
    Nature Publishing Group (NPG)
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    Publication Date: 2011-02-18
    Description: The neural fate is generally considered to be the intrinsic direction of embryonic stem (ES) cell differentiation. However, little is known about the intracellular mechanism that leads undifferentiated cells to adopt the neural fate in the absence of extrinsic inductive signals. Here we show that the zinc-finger nuclear protein Zfp521 is essential and sufficient for driving the intrinsic neural differentiation of mouse ES cells. In the absence of the neural differentiation inhibitor BMP4, strong Zfp521 expression is intrinsically induced in differentiating ES cells. Forced expression of Zfp521 enables the neural conversion of ES cells even in the presence of BMP4. Conversely, in differentiation culture, Zfp521-depleted ES cells do not undergo neural conversion but tend to halt at the epiblast state. Zfp521 directly activates early neural genes by working with the co-activator p300. Thus, the transition of ES cell differentiation from the epiblast state into neuroectodermal progenitors specifically depends on the cell-intrinsic expression and activator function of Zfp521.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kamiya, Daisuke -- Banno, Satoe -- Sasai, Noriaki -- Ohgushi, Masatoshi -- Inomata, Hidehiko -- Watanabe, Kiichi -- Kawada, Masako -- Yakura, Rieko -- Kiyonari, Hiroshi -- Nakao, Kazuki -- Jakt, Lars Martin -- Nishikawa, Shin-ichi -- Sasai, Yoshiki -- England -- Nature. 2011 Feb 24;470(7335):503-9. doi: 10.1038/nature09726. Epub 2011 Feb 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21326203" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Morphogenetic Protein 4/deficiency/genetics/metabolism ; Cadherins/metabolism ; *Cell Differentiation ; Cell Lineage ; Cells, Cultured ; Embryo, Mammalian/cytology/embryology/metabolism ; Embryonic Stem Cells/*cytology/metabolism ; Gene Expression Regulation, Developmental/genetics ; Germ Layers/cytology/embryology/metabolism ; HEK293 Cells ; Humans ; Mice ; Models, Biological ; Neural Plate/cytology/embryology/metabolism ; Neural Stem Cells/*cytology/metabolism ; Oligonucleotide Array Sequence Analysis ; SOXB1 Transcription Factors/metabolism ; Transcription Factors/deficiency/genetics/*metabolism ; Transcriptional Activation ; Xenopus ; p300-CBP Transcription Factors/metabolism
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    CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III (2011)
    Nature Publishing Group (NPG)
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    Publication Date: 2011-04-02
    Description: CRISPR/Cas systems constitute a widespread class of immunity systems that protect bacteria and archaea against phages and plasmids, and commonly use repeat/spacer-derived short crRNAs to silence foreign nucleic acids in a sequence-specific manner. Although the maturation of crRNAs represents a key event in CRISPR activation, the responsible endoribonucleases (CasE, Cas6, Csy4) are missing in many CRISPR/Cas subtypes. Here, differential RNA sequencing of the human pathogen Streptococcus pyogenes uncovered tracrRNA, a trans-encoded small RNA with 24-nucleotide complementarity to the repeat regions of crRNA precursor transcripts. We show that tracrRNA directs the maturation of crRNAs by the activities of the widely conserved endogenous RNase III and the CRISPR-associated Csn1 protein; all these components are essential to protect S. pyogenes against prophage-derived DNA. Our study reveals a novel pathway of small guide RNA maturation and the first example of a host factor (RNase III) required for bacterial RNA-mediated immunity against invaders.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3070239/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3070239/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Deltcheva, Elitza -- Chylinski, Krzysztof -- Sharma, Cynthia M -- Gonzales, Karine -- Chao, Yanjie -- Pirzada, Zaid A -- Eckert, Maria R -- Vogel, Jorg -- Charpentier, Emmanuelle -- P 17238/Austrian Science Fund FWF/Austria -- England -- Nature. 2011 Mar 31;471(7340):602-7. doi: 10.1038/nature09886.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Laboratory for Molecular Infection Medicine Sweden, Umea, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21455174" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/chemistry/genetics/immunology/metabolism ; Conserved Sequence ; DNA, Viral/genetics/metabolism ; Escherichia coli ; Models, Biological ; Prophages/genetics ; RNA Precursors/genetics/metabolism ; RNA Processing, Post-Transcriptional ; RNA, Bacterial/biosynthesis/*genetics/immunology/*metabolism ; RNA, Guide/*genetics ; Ribonuclease III/*metabolism ; Streptococcus pyogenes/*genetics/*immunology/metabolism/virology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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