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  • Molecular Sequence Data  (463)
  • Nature Publishing Group (NPG)  (463)
  • American Meteorological Society
  • Molecular Diversity Preservation International
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  • 11
    Publication Date: 2010-04-29
    Description: The nucleolytic activity of animal Argonaute proteins is deeply conserved, despite its having no obvious role in microRNA-directed gene regulation. In mice, Ago2 (also known as Eif2c2) is uniquely required for viability, and only this family member retains catalytic competence. To investigate the evolutionary pressure to conserve Argonaute enzymatic activity, we engineered a mouse with catalytically inactive Ago2 alleles. Homozygous mutants died shortly after birth with an obvious anaemia. Examination of microRNAs and their potential targets revealed a loss of miR-451, a small RNA important for erythropoiesis. Though this microRNA is processed by Drosha (also known as Rnasen), its maturation does not require Dicer. Instead, the pre-miRNA becomes loaded into Ago and is cleaved by the Ago catalytic centre to generate an intermediate 3' end, which is then further trimmed. Our findings link the conservation of Argonaute catalysis to a conserved mechanism of microRNA biogenesis that is important for vertebrate development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995450/" 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/PMC2995450/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheloufi, Sihem -- Dos Santos, Camila O -- Chong, Mark M W -- Hannon, Gregory J -- P01 CA013106/CA/NCI NIH HHS/ -- P01 CA013106-38/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Jun 3;465(7298):584-9. doi: 10.1038/nature09092.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor, New York 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20424607" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Anemia/genetics/metabolism ; Animals ; Argonaute Proteins ; Base Sequence ; *Biocatalysis ; Embryo, Mammalian/embryology/metabolism ; Eukaryotic Initiation Factor-2/genetics/*metabolism ; Homozygote ; MicroRNAs/*biosynthesis ; Molecular Sequence Data ; Ribonuclease III/metabolism
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  • 12
    Publication Date: 2010-04-20
    Description: Ever since Darwin's pioneering research, the evolution of self-fertilisation (selfing) has been regarded as one of the most prevalent evolutionary transitions in flowering plants. A major mechanism to prevent selfing is the self-incompatibility (SI) recognition system, which consists of male and female specificity genes at the S-locus and SI modifier genes. Under conditions that favour selfing, mutations disabling the male recognition component are predicted to enjoy a relative advantage over those disabling the female component, because male mutations would increase through both pollen and seeds whereas female mutations would increase only through seeds. Despite many studies on the genetic basis of loss of SI in the predominantly selfing plant Arabidopsis thaliana, it remains unknown whether selfing arose through mutations in the female specificity gene (S-receptor kinase, SRK), male specificity gene (S-locus cysteine-rich protein, SCR; also known as S-locus protein 11, SP11) or modifier genes, and whether any of them rose to high frequency across large geographic regions. Here we report that a disruptive 213-base-pair (bp) inversion in the SCR gene (or its derivative haplotypes with deletions encompassing the entire SCR-A and a large portion of SRK-A) is found in 95% of European accessions, which contrasts with the genome-wide pattern of polymorphism in European A. thaliana. Importantly, interspecific crossings using Arabidopsis halleri as a pollen donor reveal that some A. thaliana accessions, including Wei-1, retain the female SI reaction, suggesting that all female components including SRK are still functional. Moreover, when the 213-bp inversion in SCR was inverted and expressed in transgenic Wei-1 plants, the functional SCR restored the SI reaction. The inversion within SCR is the first mutation disrupting SI shown to be nearly fixed in geographically wide samples, and its prevalence is consistent with theoretical predictions regarding the evolutionary advantage of mutations in male components.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tsuchimatsu, Takashi -- Suwabe, Keita -- Shimizu-Inatsugi, Rie -- Isokawa, Sachiyo -- Pavlidis, Pavlos -- Stadler, Thomas -- Suzuki, Go -- Takayama, Seiji -- Watanabe, Masao -- Shimizu, Kentaro K -- England -- Nature. 2010 Apr 29;464(7293):1342-6. doi: 10.1038/nature08927. Epub 2010 Apr 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Plant Biology, University Research Priority Program in Systems Biology/Functional Genomics & Zurich-Basel Plant Science Center, University of Zurich, Zollikerstrasse 107, CH-8008 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20400945" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/chemistry/classification/*genetics/*physiology ; *Biological Evolution ; Crosses, Genetic ; Genes, Plant/*genetics ; Haplotypes/genetics ; Hybridization, Genetic/genetics ; Molecular Sequence Data ; Mutation/*genetics ; Pollen/physiology ; Pollination ; Reproduction/genetics/physiology
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  • 13
    Publication Date: 2010-06-04
    Description: Brown algae (Phaeophyceae) are complex photosynthetic organisms with a very different evolutionary history to green plants, to which they are only distantly related. These seaweeds are the dominant species in rocky coastal ecosystems and they exhibit many interesting adaptations to these, often harsh, environments. Brown algae are also one of only a small number of eukaryotic lineages that have evolved complex multicellularity (Fig. 1). We report the 214 million base pair (Mbp) genome sequence of the filamentous seaweed Ectocarpus siliculosus (Dillwyn) Lyngbye, a model organism for brown algae, closely related to the kelps (Fig. 1). Genome features such as the presence of an extended set of light-harvesting and pigment biosynthesis genes and new metabolic processes such as halide metabolism help explain the ability of this organism to cope with the highly variable tidal environment. The evolution of multicellularity in this lineage is correlated with the presence of a rich array of signal transduction genes. Of particular interest is the presence of a family of receptor kinases, as the independent evolution of related molecules has been linked with the emergence of multicellularity in both the animal and green plant lineages. The Ectocarpus genome sequence represents an important step towards developing this organism as a model species, providing the possibility to combine genomic and genetic approaches to explore these and other aspects of brown algal biology further.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cock, J Mark -- Sterck, Lieven -- Rouze, Pierre -- Scornet, Delphine -- Allen, Andrew E -- Amoutzias, Grigoris -- Anthouard, Veronique -- Artiguenave, Francois -- Aury, Jean-Marc -- Badger, Jonathan H -- Beszteri, Bank -- Billiau, Kenny -- Bonnet, Eric -- Bothwell, John H -- Bowler, Chris -- Boyen, Catherine -- Brownlee, Colin -- Carrano, Carl J -- Charrier, Benedicte -- Cho, Ga Youn -- Coelho, Susana M -- Collen, Jonas -- Corre, Erwan -- Da Silva, Corinne -- Delage, Ludovic -- Delaroque, Nicolas -- Dittami, Simon M -- Doulbeau, Sylvie -- Elias, Marek -- Farnham, Garry -- Gachon, Claire M M -- Gschloessl, Bernhard -- Heesch, Svenja -- Jabbari, Kamel -- Jubin, Claire -- Kawai, Hiroshi -- Kimura, Kei -- Kloareg, Bernard -- Kupper, Frithjof C -- Lang, Daniel -- Le Bail, Aude -- Leblanc, Catherine -- Lerouge, Patrice -- Lohr, Martin -- Lopez, Pascal J -- Martens, Cindy -- Maumus, Florian -- Michel, Gurvan -- Miranda-Saavedra, Diego -- Morales, Julia -- Moreau, Herve -- Motomura, Taizo -- Nagasato, Chikako -- Napoli, Carolyn A -- Nelson, David R -- Nyvall-Collen, Pi -- Peters, Akira F -- Pommier, Cyril -- Potin, Philippe -- Poulain, Julie -- Quesneville, Hadi -- Read, Betsy -- Rensing, Stefan A -- Ritter, Andres -- Rousvoal, Sylvie -- Samanta, Manoj -- Samson, Gaelle -- Schroeder, Declan C -- Segurens, Beatrice -- Strittmatter, Martina -- Tonon, Thierry -- Tregear, James W -- Valentin, Klaus -- von Dassow, Peter -- Yamagishi, Takahiro -- Van de Peer, Yves -- Wincker, Patrick -- England -- Nature. 2010 Jun 3;465(7298):617-21. doi: 10.1038/nature09016.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉UPMC Universite Paris 6, The Marine Plants and Biomolecules Laboratory, UMR 7139, Station Biologique de Roscoff, Place Georges Teissier, BP74, 29682 Roscoff Cedex, France. cock@sb-roscoff.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20520714" target="_blank"〉PubMed〈/a〉
    Keywords: Algal Proteins/*genetics ; Animals ; *Biological Evolution ; Eukaryota ; Evolution, Molecular ; Genome/*genetics ; Molecular Sequence Data ; Phaeophyta/*cytology/*genetics/metabolism ; Phylogeny ; Pigments, Biological/biosynthesis ; Signal Transduction/genetics
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  • 14
    Publication Date: 2010-05-21
    Description: The need to maintain the structural and functional integrity of an evolving protein severely restricts the repertoire of acceptable amino-acid substitutions. However, it is not known whether these restrictions impose a global limit on how far homologous protein sequences can diverge from each other. Here we explore the limits of protein evolution using sequence divergence data. We formulate a computational approach to study the rate of divergence of distant protein sequences and measure this rate for ancient proteins, those that were present in the last universal common ancestor. We show that ancient proteins are still diverging from each other, indicating an ongoing expansion of the protein sequence universe. The slow rate of this divergence is imposed by the sparseness of functional protein sequences in sequence space and the ruggedness of the protein fitness landscape: approximately 98 per cent of sites cannot accept an amino-acid substitution at any given moment but a vast majority of all sites may eventually be permitted to evolve when other, compensatory, changes occur. Thus, approximately 3.5 x 10(9) yr has not been enough to reach the limit of divergent evolution of proteins, and for most proteins the limit of sequence similarity imposed by common function may not exceed that of random sequences.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Povolotskaya, Inna S -- Kondrashov, Fyodor A -- England -- Nature. 2010 Jun 17;465(7300):922-6. doi: 10.1038/nature09105. Epub 2010 May 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bioinformatics and Genomics Programme, Centre for Genomic Regulation, Calle Dr Aiguader 88, Barcelona Biomedical Research Park Building, 08003 Barcelona, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20485343" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Amino Acids/chemistry ; *Evolution, Molecular ; *Genetic Variation ; Molecular Sequence Data ; Mutation ; Prokaryotic Cells ; Protein Structure, Secondary ; Proteins/*chemistry ; Selection, Genetic/genetics ; Sequence Analysis, Protein ; Sequence Homology, Amino Acid
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  • 15
    Publication Date: 2010-01-15
    Description: All immune systems must distinguish self from non-self to repel invaders without inducing autoimmunity. Clustered, regularly interspaced, short palindromic repeat (CRISPR) loci protect bacteria and archaea from invasion by phage and plasmid DNA through a genetic interference pathway. CRISPR loci are present in approximately 40% and approximately 90% of sequenced bacterial and archaeal genomes, respectively, and evolve rapidly, acquiring new spacer sequences to adapt to highly dynamic viral populations. Immunity requires a sequence match between the invasive DNA and the spacers that lie between CRISPR repeats. Each cluster is genetically linked to a subset of the cas (CRISPR-associated) genes that collectively encode 〉40 families of proteins involved in adaptation and interference. CRISPR loci encode small CRISPR RNAs (crRNAs) that contain a full spacer flanked by partial repeat sequences. CrRNA spacers are thought to identify targets by direct Watson-Crick pairing with invasive 'protospacer' DNA, but how they avoid targeting the spacer DNA within the encoding CRISPR locus itself is unknown. Here we have defined the mechanism of CRISPR self/non-self discrimination. In Staphylococcus epidermidis, target/crRNA mismatches at specific positions outside of the spacer sequence license foreign DNA for interference, whereas extended pairing between crRNA and CRISPR DNA repeats prevents autoimmunity. Hence, this CRISPR system uses the base-pairing potential of crRNAs not only to specify a target, but also to spare the bacterial chromosome from interference. Differential complementarity outside of the spacer sequence is a built-in feature of all CRISPR systems, indicating that this mechanism is a broadly applicable solution to the self/non-self dilemma that confronts all immune pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813891/" 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/PMC2813891/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marraffini, Luciano A -- Sontheimer, Erik J -- R03 AI079722/AI/NIAID NIH HHS/ -- R03 AI079722-01A1/AI/NIAID NIH HHS/ -- England -- Nature. 2010 Jan 28;463(7280):568-71. doi: 10.1038/nature08703. Epub 2010 Jan 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, 2205 Tech Drive, Evanston, Illinois 60208, USA. marraffini@northwestern.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20072129" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/genetics ; Base Pairing/genetics ; Base Sequence ; Conserved Sequence ; DNA, Intergenic/genetics ; Molecular Sequence Data ; Mutation/genetics ; RNA, Bacterial/*genetics/metabolism ; Repetitive Sequences, Nucleic Acid/*genetics/*immunology ; Staphylococcus epidermidis/*genetics/*immunology
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  • 16
    Publication Date: 2010-11-05
    Description: Bacteria and Archaea have developed several defence strategies against foreign nucleic acids such as viral genomes and plasmids. Among them, clustered regularly interspaced short palindromic repeats (CRISPR) loci together with cas (CRISPR-associated) genes form the CRISPR/Cas immune system, which involves partially palindromic repeats separated by short stretches of DNA called spacers, acquired from extrachromosomal elements. It was recently demonstrated that these variable loci can incorporate spacers from infecting bacteriophages and then provide immunity against subsequent bacteriophage infections in a sequence-specific manner. Here we show that the Streptococcus thermophilus CRISPR1/Cas system can also naturally acquire spacers from a self-replicating plasmid containing an antibiotic-resistance gene, leading to plasmid loss. Acquired spacers that match antibiotic-resistance genes provide a novel means to naturally select bacteria that cannot uptake and disseminate such genes. We also provide in vivo evidence that the CRISPR1/Cas system specifically cleaves plasmid and bacteriophage double-stranded DNA within the proto-spacer, at specific sites. Our data show that the CRISPR/Cas immune system is remarkably adapted to cleave invading DNA rapidly and has the potential for exploitation to generate safer microbial strains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garneau, Josiane E -- Dupuis, Marie-Eve -- Villion, Manuela -- Romero, Dennis A -- Barrangou, Rodolphe -- Boyaval, Patrick -- Fremaux, Christophe -- Horvath, Philippe -- Magadan, Alfonso H -- Moineau, Sylvain -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2010 Nov 4;468(7320):67-71. doi: 10.1038/nature09523.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departement de biochimie, de microbiologie et de bio-informatique, Faculte des sciences et de genie, Groupe de recherche en ecologie buccale, Faculte de medecine dentaire, Felix d'Herelle Reference Center for Bacterial Viruses, Universite Laval, Quebec City, Quebec G1V 0A6, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21048762" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteriophages/*genetics/metabolism ; Base Sequence ; DNA, Intergenic/genetics/metabolism ; DNA, Viral/genetics/*metabolism ; Drug Resistance, Bacterial/genetics ; Genetic Loci/*genetics/*immunology ; Interspersed Repetitive Sequences/genetics ; Molecular Sequence Data ; Mutation ; Plasmids/genetics/*metabolism ; RNA, Bacterial/genetics/immunology ; Streptococcus thermophilus/genetics/*immunology/*virology
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  • 17
    Publication Date: 2010-02-26
    Description: Despite the essential roles of sphingolipids both as structural components of membranes and critical signalling molecules, we have a limited understanding of how cells sense and regulate their levels. Here we reveal the function in sphingolipid metabolism of the ORM genes (known as ORMDL genes in humans)-a conserved gene family that includes ORMDL3, which has recently been identified as a potential risk factor for childhood asthma. Starting from an unbiased functional genomic approach in Saccharomyces cerevisiae, we identify Orm proteins as negative regulators of sphingolipid synthesis that form a conserved complex with serine palmitoyltransferase, the first and rate-limiting enzyme in sphingolipid production. We also define a regulatory pathway in which phosphorylation of Orm proteins relieves their inhibitory activity when sphingolipid production is disrupted. Changes in ORM gene expression or mutations to their phosphorylation sites cause dysregulation of sphingolipid metabolism. Our work identifies the Orm proteins as critical mediators of sphingolipid homeostasis and raises the possibility that sphingolipid misregulation contributes to the development of childhood asthma.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877384/" 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/PMC2877384/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Breslow, David K -- Collins, Sean R -- Bodenmiller, Bernd -- Aebersold, Ruedi -- Simons, Kai -- Shevchenko, Andrej -- Ejsing, Christer S -- Weissman, Jonathan S -- N01-HV-28179/HV/NHLBI NIH HHS/ -- P50 GM073210/GM/NIGMS NIH HHS/ -- P50 GM073210-06/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Feb 25;463(7284):1048-53. doi: 10.1038/nature08787.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 1700 4th Street, San Francisco, California 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20182505" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Asthma/metabolism ; Cell Line ; Conserved Sequence ; Fatty Acids, Monounsaturated/pharmacology ; HeLa Cells ; *Homeostasis ; Humans ; Molecular Sequence Data ; *Multigene Family ; Multiprotein Complexes/chemistry/metabolism ; Phosphoric Monoester Hydrolases/genetics/metabolism ; Phosphorylation ; Protein Binding ; Saccharomyces cerevisiae/drug effects/enzymology/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/classification/genetics/*metabolism ; Serine C-Palmitoyltransferase/genetics/metabolism ; Sphingolipids/biosynthesis/*metabolism
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  • 18
    Publication Date: 2010-03-09
    Description: The tumour suppressor ARF is specifically required for p53 activation under oncogenic stress. Recent studies showed that p53 activation mediated by ARF, but not that induced by DNA damage, acts as a major protection against tumorigenesis in vivo under certain biological settings, suggesting that the ARF-p53 axis has more fundamental functions in tumour suppression than originally thought. Because ARF is a very stable protein in most human cell lines, it has been widely assumed that ARF induction is mediated mainly at the transcriptional level and that activation of the ARF-p53 pathway by oncogenes is a much slower and largely irreversible process by comparison with p53 activation after DNA damage. Here we report that ARF is very unstable in normal human cells but that its degradation is inhibited in cancerous cells. Through biochemical purification, we identified a specific ubiquitin ligase for ARF and named it ULF. ULF interacts with ARF both in vitro and in vivo and promotes the lysine-independent ubiquitylation and degradation of ARF. ULF knockdown stabilizes ARF in normal human cells, triggering ARF-dependent, p53-mediated growth arrest. Moreover, nucleophosmin (NPM) and c-Myc, both of which are commonly overexpressed in cancer cells, are capable of abrogating ULF-mediated ARF ubiquitylation through distinct mechanisms, and thereby promote ARF stabilization in cancer cells. These findings reveal the dynamic feature of the ARF-p53 pathway and suggest that transcription-independent mechanisms are critically involved in ARF regulation during responses to oncogenic stress.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737736/" 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/PMC3737736/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Delin -- Shan, Jing -- Zhu, Wei-Guo -- Qin, Jun -- Gu, Wei -- P01 CA080058/CA/NCI NIH HHS/ -- P01 CA097403/CA/NCI NIH HHS/ -- R01 CA085533/CA/NCI NIH HHS/ -- R01 CA118561/CA/NCI NIH HHS/ -- R01 CA129627/CA/NCI NIH HHS/ -- R01 CA131439/CA/NCI NIH HHS/ -- England -- Nature. 2010 Mar 25;464(7288):624-7. doi: 10.1038/nature08820. Epub 2010 Mar 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Cancer Genetics, and Department of Pathology and Cell Biology College of Physicians & Surgeons, Columbia University, 1130 St Nicholas Avenue, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20208519" target="_blank"〉PubMed〈/a〉
    Keywords: ADP-Ribosylation Factors/*metabolism ; Cell Line ; Fibroblasts/metabolism ; *Gene Expression Regulation ; Humans ; Molecular Sequence Data ; Nuclear Proteins/metabolism ; Proto-Oncogene Proteins c-myc/metabolism ; Stress, Physiological/*physiology ; Tumor Suppressor Protein p53/*metabolism ; U937 Cells ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination
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  • 19
    Publication Date: 2010-02-02
    Description: The spectacular escalation in complexity in early bilaterian evolution correlates with a strong increase in the number of microRNAs. To explore the link between the birth of ancient microRNAs and body plan evolution, we set out to determine the ancient sites of activity of conserved bilaterian microRNA families in a comparative approach. We reason that any specific localization shared between protostomes and deuterostomes (the two major superphyla of bilaterian animals) should probably reflect an ancient specificity of that microRNA in their last common ancestor. Here, we investigate the expression of conserved bilaterian microRNAs in Platynereis dumerilii, a protostome retaining ancestral bilaterian features, in Capitella, another marine annelid, in the sea urchin Strongylocentrotus, a deuterostome, and in sea anemone Nematostella, representing an outgroup to the bilaterians. Our comparative data indicate that the oldest known animal microRNA, miR-100, and the related miR-125 and let-7 were initially active in neurosecretory cells located around the mouth. Other sets of ancient microRNAs were first present in locomotor ciliated cells, specific brain centres, or, more broadly, one of four major organ systems: central nervous system, sensory tissue, musculature and gut. These findings reveal that microRNA evolution and the establishment of tissue identities were closely coupled in bilaterian evolution. Also, they outline a minimum set of cell types and tissues that existed in the protostome-deuterostome ancestor.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981144/" 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/PMC2981144/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Christodoulou, Foteini -- Raible, Florian -- Tomer, Raju -- Simakov, Oleg -- Trachana, Kalliopi -- Klaus, Sebastian -- Snyman, Heidi -- Hannon, Gregory J -- Bork, Peer -- Arendt, Detlev -- P01 CA013106/CA/NCI NIH HHS/ -- P01 CA013106-38/CA/NCI NIH HHS/ -- P01 CA013106-39/CA/NCI NIH HHS/ -- England -- Nature. 2010 Feb 25;463(7284):1084-8. doi: 10.1038/nature08744. Epub 2010 Jan 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental Biology Unit, European Molecular Biology Laboratory, D-69117 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20118916" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Annelida/anatomy & histology/cytology/genetics ; *Biological Evolution ; Brain/metabolism ; Cilia/physiology ; Conserved Sequence/genetics ; Digestive System/cytology/metabolism ; In Situ Hybridization ; MicroRNAs/*analysis/*genetics ; Molecular Sequence Data ; *Organ Specificity ; Phylogeny ; Polychaeta/*anatomy & histology/cytology/*genetics ; Sea Anemones/anatomy & histology/cytology/genetics ; Sea Urchins/anatomy & histology/cytology/genetics
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  • 20
    Publication Date: 2010-09-28
    Description: Epigenetic proteins are intently pursued targets in ligand discovery. So far, successful efforts have been limited to chromatin modifying enzymes, or so-called epigenetic 'writers' and 'erasers'. Potent inhibitors of histone binding modules have not yet been described. Here we report a cell-permeable small molecule (JQ1) that binds competitively to acetyl-lysine recognition motifs, or bromodomains. High potency and specificity towards a subset of human bromodomains is explained by co-crystal structures with bromodomain and extra-terminal (BET) family member BRD4, revealing excellent shape complementarity with the acetyl-lysine binding cavity. Recurrent translocation of BRD4 is observed in a genetically-defined, incurable subtype of human squamous carcinoma. Competitive binding by JQ1 displaces the BRD4 fusion oncoprotein from chromatin, prompting squamous differentiation and specific antiproliferative effects in BRD4-dependent cell lines and patient-derived xenograft models. These data establish proof-of-concept for targeting protein-protein interactions of epigenetic 'readers', and provide a versatile chemical scaffold for the development of chemical probes more broadly throughout the bromodomain family.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010259/" 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/PMC3010259/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Filippakopoulos, Panagis -- Qi, Jun -- Picaud, Sarah -- Shen, Yao -- Smith, William B -- Fedorov, Oleg -- Morse, Elizabeth M -- Keates, Tracey -- Hickman, Tyler T -- Felletar, Ildiko -- Philpott, Martin -- Munro, Shonagh -- McKeown, Michael R -- Wang, Yuchuan -- Christie, Amanda L -- West, Nathan -- Cameron, Michael J -- Schwartz, Brian -- Heightman, Tom D -- La Thangue, Nicholas -- French, Christopher A -- Wiest, Olaf -- Kung, Andrew L -- Knapp, Stefan -- Bradner, James E -- 13058/Cancer Research UK/United Kingdom -- G0500905/Medical Research Council/United Kingdom -- G1000807/Medical Research Council/United Kingdom -- G9400953/Medical Research Council/United Kingdom -- K08 CA128972/CA/NCI NIH HHS/ -- K08 CA128972-03/CA/NCI NIH HHS/ -- T32-075762/PHS HHS/ -- Canadian Institutes of Health Research/Canada -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Dec 23;468(7327):1067-73. doi: 10.1038/nature09504. Epub 2010 Sep 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20871596" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Azirines/chemical synthesis/chemistry/*pharmacology ; Binding Sites ; Carcinoma, Squamous Cell/physiopathology ; Cell Differentiation/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Chromatin/metabolism ; Dihydropyridines/chemical synthesis/chemistry/*pharmacology ; Female ; Humans ; Mice ; Mice, Nude ; *Models, Molecular ; Molecular Sequence Data ; Nuclear Proteins/*antagonists & inhibitors/*metabolism ; Protein Binding/drug effects ; Protein Structure, Tertiary ; Recombinant Proteins/metabolism ; Sequence Alignment ; Skin Neoplasms/physiopathology ; Stereoisomerism ; Transcription Factors/*antagonists & inhibitors/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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