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  • 1
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    An essential role for DNA adenine methylation in bacterial virulence (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-05-13
    Description: Salmonella typhimurium lacking DNA adenine methylase (Dam) were fully proficient in colonization of mucosal sites but showed severe defects in colonization of deeper tissue sites. These Dam- mutants were totally avirulent and were effective as live vaccines against murine typhoid fever. Dam regulated the expression of at least 20 genes known to be induced during infection; a subset of these genes are among those activated by the PhoP global virulence regulator. PhoP, in turn, affected Dam methylation at specific genomic sites, as evidenced by alterations in DNA methylation patterns. Dam inhibitors are likely to have broad antimicrobial action, and Dam- derivatives of these pathogens may serve as live attenuated vaccines.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heithoff, D M -- Sinsheimer, R L -- Low, D A -- Mahan, M J -- AI23348/AI/NIAID NIH HHS/ -- AI36373/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1999 May 7;284(5416):967-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10320378" target="_blank"〉PubMed〈/a〉
    Keywords: Adenine/metabolism ; Animals ; Bacterial Proteins/metabolism ; *Bacterial Vaccines ; *DNA Methylation ; DNA, Bacterial/metabolism ; Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Lethal Dose 50 ; Methylation ; Mice ; Mice, Inbred BALB C ; Mutation ; Peyer's Patches/microbiology ; Salmonella Infections, Animal/immunology/*microbiology/prevention & control ; Salmonella typhimurium/*enzymology/genetics/immunology/*pathogenicity ; Site-Specific DNA-Methyltransferase (Adenine-Specific)/antagonists & ; inhibitors/genetics/*metabolism ; Vaccines, Attenuated ; Virulence/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    Restricted lateral diffusion of PH-20, a PI-anchored sperm membrane protein (1988)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1988-06-24
    Description: The rate of lateral diffusion of integral membrane proteins is constrained in cells, but the constraining factors for most membrane proteins have not been defined. PH-20, a sperm surface protein involved in sperm-egg adhesion, was shown to be anchored in the plasma membrane by attachment to the lipid phosphatidylinositol and to have a diffusion rate that is highly restricted on testicular sperm, being more than a thousand times slower than lipid diffusion. These results support the hypothesis that lateral mobility of a membrane protein can be regulated exclusively by interactions of its ectodomain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Phelps, B M -- Primakoff, P -- Koppel, D E -- Low, M G -- Myles, D G -- GM-23585/GM/NIGMS NIH HHS/ -- HD-16580/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1988 Jun 24;240(4860):1780-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of Connecticut Health Center, Farmington 06032.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3381102" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Surface ; Cell Adhesion Molecules ; Cell Compartmentation ; Cell Membrane/physiology ; Diffusion ; Guinea Pigs ; Male ; *Membrane Fluidity ; Membrane Proteins/*physiology ; Phosphatidylinositols/*physiology ; Sperm Maturation ; Spermatozoa/*physiology ; Testis/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    Synaptic vesicle endocytosis impaired by disruption of dynamin-SH3 domain interactions (1997)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1997-04-11
    Description: The proline-rich COOH-terminal region of dynamin binds various Src homology 3 (SH3) domain-containing proteins, but the physiological role of these interactions is unknown. In living nerve terminals, the function of the interaction with SH3 domains was examined. Amphiphysin contains an SH3 domain and is a major dynamin binding partner at the synapse. Microinjection of amphiphysin's SH3 domain or of a dynamin peptide containing the SH3 binding site inhibited synaptic vesicle endocytosis at the stage of invaginated clathrin-coated pits, which resulted in an activity-dependent distortion of the synaptic architecture and a depression of transmitter release. These findings demonstrate that SH3-mediated interactions are required for dynamin function and support an essential role of clathrin-mediated endocytosis in synaptic vesicle recycling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shupliakov, O -- Low, P -- Grabs, D -- Gad, H -- Chen, H -- David, C -- Takei, K -- De Camilli, P -- Brodin, L -- CA46128/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1997 Apr 11;276(5310):259-63.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9092476" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Cell Membrane/ultrastructure ; Coated Pits, Cell-Membrane/ultrastructure ; Dynamins ; *Endocytosis ; GTP Phosphohydrolases/*metabolism ; Humans ; Lampreys ; Microscopy, Electron ; Molecular Sequence Data ; Nerve Tissue Proteins/chemistry/*metabolism ; Proline/chemistry ; Recombinant Fusion Proteins/metabolism ; Synapses/metabolism/ultrastructure ; Synaptic Transmission ; Synaptic Vesicles/*metabolism/ultrastructure ; *src Homology Domains
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-08-17
    Description: LGR5+ stem cells reside at crypt bottoms, intermingled with Paneth cells that provide Wnt, Notch and epidermal growth factor signals. Here we find that the related RNF43 and ZNRF3 transmembrane E3 ubiquitin ligases are uniquely expressed in LGR5+ stem cells. Simultaneous deletion of the two genes encoding these proteins in the intestinal epithelium of mice induces rapidly growing adenomas containing high numbers of Paneth and LGR5+ stem cells. In vitro, growth of organoids derived from these adenomas is arrested when Wnt secretion is inhibited, indicating a dependence of the adenoma stem cells on Wnt produced by adenoma Paneth cells. In the HEK293T human cancer cell line, expression of RNF43 blocks Wnt responses and targets surface-expressed frizzled receptors to lysosomes. In the RNF43-mutant colorectal cancer cell line HCT116, reconstitution of RNF43 expression removes its response to exogenous Wnt. We conclude that RNF43 and ZNRF3 reduce Wnt signals by selectively ubiquitinating frizzled receptors, thereby targeting these Wnt receptors for degradation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Koo, Bon-Kyoung -- Spit, Maureen -- Jordens, Ingrid -- Low, Teck Y -- Stange, Daniel E -- van de Wetering, Marc -- van Es, Johan H -- Mohammed, Shabaz -- Heck, Albert J R -- Maurice, Madelon M -- Clevers, Hans -- England -- Nature. 2012 Aug 30;488(7413):665-9. doi: 10.1038/nature11308.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Hubrecht Institute, KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22895187" target="_blank"〉PubMed〈/a〉
    Keywords: Adenoma/metabolism/pathology ; Animals ; Cell Proliferation ; Colorectal Neoplasms/metabolism/pathology ; DNA-Binding Proteins/deficiency/genetics/*metabolism ; *Endocytosis ; Frizzled Receptors/metabolism ; HEK293 Cells ; Humans ; Lysosomes/metabolism ; Mice ; Oncogene Proteins/deficiency/genetics/*metabolism ; Organoids/cytology/metabolism/pathology ; Paneth Cells/metabolism/pathology ; Receptors, G-Protein-Coupled/genetics/metabolism ; Receptors, Wnt/antagonists & inhibitors/*metabolism ; Stem Cells/cytology/*enzymology/metabolism ; Tumor Suppressor Proteins/deficiency/genetics/*metabolism ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/deficiency/genetics/*metabolism ; Ubiquitination ; *Wnt Signaling Pathway/drug effects ; beta Catenin/metabolism
    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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  • 5
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    Selective transcriptional regulation by Myc in cellular growth control and lymphomagenesis (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-07-22
    Description: The c-myc proto-oncogene product, Myc, is a transcription factor that binds thousands of genomic loci. Recent work suggested that rather than up- and downregulating selected groups of genes, Myc targets all active promoters and enhancers in the genome (a phenomenon termed 'invasion') and acts as a general amplifier of transcription. However, the available data did not readily discriminate between direct and indirect effects of Myc on RNA biogenesis. We addressed this issue with genome-wide chromatin immunoprecipitation and RNA expression profiles during B-cell lymphomagenesis in mice, in cultured B cells and fibroblasts. Consistent with long-standing observations, we detected general increases in total RNA or messenger RNA copies per cell (hereby termed 'amplification') when comparing actively proliferating cells with control quiescent cells: this was true whether cells were stimulated by mitogens (requiring endogenous Myc for a proliferative response) or by deregulated, oncogenic Myc activity. RNA amplification and promoter/enhancer invasion by Myc were separable phenomena that could occur without one another. Moreover, whether or not associated with RNA amplification, Myc drove the differential expression of distinct subsets of target genes. Hence, although having the potential to interact with all active or poised regulatory elements in the genome, Myc does not directly act as a global transcriptional amplifier. Instead, our results indicate that Myc activates and represses transcription of discrete gene sets, leading to changes in cellular state that can in turn feed back on global RNA production and turnover.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110711/" 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/PMC4110711/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sabo, Arianna -- Kress, Theresia R -- Pelizzola, Mattia -- de Pretis, Stefano -- Gorski, Marcin M -- Tesi, Alessandra -- Morelli, Marco J -- Bora, Pranami -- Doni, Mirko -- Verrecchia, Alessandro -- Tonelli, Claudia -- Faga, Giovanni -- Bianchi, Valerio -- Ronchi, Alberto -- Low, Diana -- Muller, Heiko -- Guccione, Ernesto -- Campaner, Stefano -- Amati, Bruno -- 10-0245/Worldwide Cancer Research/United Kingdom -- 268671/European Research Council/International -- England -- Nature. 2014 Jul 24;511(7510):488-92. doi: 10.1038/nature13537. Epub 2014 Jul 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), Via Adamello 16, 20139 Milan, Italy [2] Department of Experimental Oncology, European Institute of Oncology (IEO), Via Adamello 16, 20139 Milan, Italy [3]. ; 1] Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), Via Adamello 16, 20139 Milan, Italy [2]. ; Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), Via Adamello 16, 20139 Milan, Italy. ; Department of Experimental Oncology, European Institute of Oncology (IEO), Via Adamello 16, 20139 Milan, Italy. ; Institute of Molecular and Cell Biology, Singapore 138673, Singapore. ; 1] Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), Via Adamello 16, 20139 Milan, Italy [2] Department of Experimental Oncology, European Institute of Oncology (IEO), Via Adamello 16, 20139 Milan, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043028" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/metabolism/pathology ; *Cell Proliferation ; Cell Transformation, Neoplastic/*genetics/pathology ; Chromatin/genetics/metabolism ; Chromatin Immunoprecipitation ; Disease Progression ; Down-Regulation/genetics ; Female ; Fibroblasts/cytology/metabolism ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic/genetics ; Genome/genetics ; Lymphoma, B-Cell/*genetics/metabolism/*pathology ; Male ; Mice ; Mitogens/pharmacology ; Promoter Regions, Genetic/genetics ; Proto-Oncogene Proteins c-myc/genetics/*metabolism ; RNA, Messenger/biosynthesis/genetics/metabolism ; Transcription Factors/metabolism ; *Transcription, Genetic/genetics ; Up-Regulation/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
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    Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling (2011)
    Nature Publishing Group (NPG)
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    Publication Date: 2011-07-06
    Description: The adult stem cell marker Lgr5 and its relative Lgr4 are often co-expressed in Wnt-driven proliferative compartments. We find that conditional deletion of both genes in the mouse gut impairs Wnt target gene expression and results in the rapid demise of intestinal crypts, thus phenocopying Wnt pathway inhibition. Mass spectrometry demonstrates that Lgr4 and Lgr5 associate with the Frizzled/Lrp Wnt receptor complex. Each of the four R-spondins, secreted Wnt pathway agonists, can bind to Lgr4, -5 and -6. In HEK293 cells, RSPO1 enhances canonical WNT signals initiated by WNT3A. Removal of LGR4 does not affect WNT3A signalling, but abrogates the RSPO1-mediated signal enhancement, a phenomenon rescued by re-expression of LGR4, -5 or -6. Genetic deletion of Lgr4/5 in mouse intestinal crypt cultures phenocopies withdrawal of Rspo1 and can be rescued by Wnt pathway activation. Lgr5 homologues are facultative Wnt receptor components that mediate Wnt signal enhancement by soluble R-spondin proteins. These results will guide future studies towards the application of R-spondins for regenerative purposes of tissues expressing Lgr5 homologues.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Lau, Wim -- Barker, Nick -- Low, Teck Y -- Koo, Bon-Kyoung -- Li, Vivian S W -- Teunissen, Hans -- Kujala, Pekka -- Haegebarth, Andrea -- Peters, Peter J -- van de Wetering, Marc -- Stange, Daniel E -- van Es, Johan E -- Guardavaccaro, Daniele -- Schasfoort, Richard B M -- Mohri, Yasuaki -- Nishimori, Katsuhiko -- Mohammed, Shabaz -- Heck, Albert J R -- Clevers, Hans -- England -- Nature. 2011 Jul 4;476(7360):293-7. doi: 10.1038/nature10337.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Hubrecht Institute and University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21727895" target="_blank"〉PubMed〈/a〉
    Keywords: Adult Stem Cells/metabolism ; Animals ; Cells, Cultured ; Epithelial Cells/cytology/metabolism ; Frizzled Receptors/metabolism ; Gene Deletion ; HEK293 Cells ; Humans ; Mice ; Protein Binding ; Protein Structure, Tertiary ; Receptors, G-Protein-Coupled/chemistry/deficiency/genetics/*metabolism ; Regeneration ; *Signal Transduction/genetics ; Thrombospondins/*metabolism ; Wnt Proteins/genetics/*metabolism ; Wnt3 Protein ; Wnt3A Protein
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
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    Gonadotroph-specific expression of metallothionein fusion genes in pituitaries of transgenic mice (1986)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1986-02-28
    Description: Transgenic mice expressing a metallothionein-somatostatin fusion gene contain high concentrations of somatostatin in the anterior pituitary gland, a tissue that does not normally produce somatostatin. Immunoreactive somatostatin within the anterior pituitaries was found exclusively within gonadotrophs. Similarly, a metallothionein-human growth-hormone fusion gene was also expressed selectively in gonadotrophs. It is proposed that sequences common to the two fusion genes are responsible for the gonadotroph-specific expression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Low, M J -- Lechan, R M -- Hammer, R E -- Brinster, R L -- Habener, J F -- Mandel, G -- Goodman, R H -- AM 01313/AM/NIADDK NIH HHS/ -- AM 30457/AM/NIADDK NIH HHS/ -- AM 31400/AM/NIADDK NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1986 Feb 28;231(4741):1002-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2868526" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; DNA, Recombinant/metabolism ; Genes ; Genetic Engineering ; Humans ; Immunoenzyme Techniques ; Luteinizing Hormone/metabolism ; Metallothionein/*genetics ; Mice ; Pituitary Gland, Anterior/*metabolism ; Rats ; Somatostatin/*genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    Structural and functional roles of glycosyl-phosphatidylinositol in membranes (1988)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1988-01-15
    Description: Glycosylated forms of phosphatidylinositol, which have only recently been described in eukaryotic organisms, are now known to play important roles in biological membrane function. These molecules can serve as the sole means by which particular cell-surface proteins are anchored to the membrane. Lipids with similar structures may also be involved in signal transduction mechanisms for the hormone insulin. The utilization of this novel class of lipid molecules for these two distinct functions suggests new mechanisms for the regulation of proteins in biological membranes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Low, M G -- Saltiel, A R -- DK33804/DK/NIDDK NIH HHS/ -- GM35873/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1988 Jan 15;239(4837):268-75.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons of Columbia University, New York, NY 10032.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3276003" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Membrane/*physiology ; Chemical Phenomena ; Chemistry ; Glycolipids/biosynthesis/*physiology ; Glycosylation ; Humans ; Hydrolysis ; Insulin/physiology ; Membrane Lipids/physiology ; Membrane Proteins/physiology ; Phosphatidylinositols/biosynthesis/*physiology ; Phospholipases/metabolism ; Phospholipid Ethers/biosynthesis/physiology ; Trypanosoma brucei brucei/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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