8,430 research outputs found
Arylsulfatase G, a novel lysosomal sulfatase
No full textFrese M-A, Schulz S, Dierks T. Arylsulfatase G, a novel lysosomal sulfatase. JOURNAL OF BIOLOGICAL CHEMISTRY. 2008;283(17):11388-11395.The sulfatases constitute a conserved family of enzymes that specifically hydrolyze sulfate esters in a wide variety of substrates such as glycosaminoglycans, steroid sulfates, or sulfolipids. By modifying the sulfation state of their substrates, sulfatases play a key role in the control of physiological processes, including cellular degradation, cell signaling, and hormone regulation. The loss of sulfatase activity has been linked with various severe pathophysiological conditions such as lysosomal storage disorders, developmental abnormalities, or cancer. A novel member of this family, arylsulfatase G (ASG), was initially described as an enzyme lacking in vitro arylsulfatase activity and localizing to the endoplasmic reticulum. Contrary to these results, we demonstrate here that ASG does indeed have arylsulfatase activity toward different pseudosubstrates like p-nitrocatechol sulfate and 4-methylumbelliferyl sulfate. The activity of ASG depends on the Cys-84 residue that is predicted to be post-translationally converted to the critical active site C-alpha-formylglycine. Phosphate acts as a strong, competitive ASG inhibitor. ASG is active as an unprocessed 63-kDa monomer and shows an acidic pH optimum as typically seen for lysosomal sulfatases. In transfected cells, ASG accumulates within lysosomes as indicated by indirect immunofluorescence microscopy. Furthermore, ASG is a glycoprotein that binds specifically to mannose 6-phosphate receptors, corroborating its lysosomal localization. ARSG mRNA expression was found to be tissue-specific with highest expression in liver, kidney, and pancreas, suggesting a metabolic role of ASG that might be associated with a so far non-classified lysosomal storage disorder
Sulf loss influences N-, 2-O-, and 6-O-sulfation of multiple heparan sulfate proteoglycans and modulates fibroblast growth factor signaling
No full textLamanna WC, Frese M-A, Balleininger M, Dierks T. Sulf loss influences N-, 2-O-, and 6-O-sulfation of multiple heparan sulfate proteoglycans and modulates fibroblast growth factor signaling. JOURNAL OF BIOLOGICAL CHEMISTRY. 2008;283(41):27724-27735.Sulf1 and Sulf2 are two heparan sulfate 6-O-endosulfatases that regulate the activity of multiple growth factors, such as fibroblast growth factor and Wnt, and are essential for mammalian development and survival. In this study, the mammalian Sulfs were functionally characterized using overexpressing cell lines, in vitro enzyme assays, and in vivo Sulf knock-out cell models. Analysis of subcellular Sulf localization revealed significant differences in enzyme secretion and detergent solubility between the human isoforms and their previously characterized quail orthologs. Further, the activity of the Sulfs toward their native heparan sulfate substrates was determined in vitro, demonstrating restricted specificity for S-domain-associated 6S disaccharides and an inability to modify transition zone-associated UA-GlcNAc( 6S). Analysis of heparan sulfate composition from different cell surface, shed, glycosylphosphatidylinositol- anchored and extracellular matrix proteoglycan fractions of Sulf knock-out cell lines established differential effects of Sulf1 and/or Sulf2 loss on nonsubstrate N-, 2-O-, and 6-O-sulfate groups. These findings indicate a dynamic influence of Sulf deficiency on the HS biosynthetic machinery. Real time PCR analysis substantiated differential expression of the Hs2st and Hs6st heparan sulfate sulfotransferase enzymes in the Sulf knock-out cell lines. Functionally, the changes in heparan sulfate sulfation resulting from Sulf loss were shown to elicit significant effects on fibroblast growth factor signaling. Taken together, this study implicates that the Sulfs are involved in a potential cellular feed-back mechanism, in which they edit the sulfation of multiple heparan sulfate proteoglycans, thereby regulating cellular signaling and modulating the expression of heparan sulfate biosynthetic enzymes
Molecular basis of multiple sulfatase deficiency, mucolipidosis II/III and Niemann-Pick C1 disease - Lysosomal storage disorders caused by defects of non-lysosomal proteins
No full textDierks T, Schlotawa L, Frese M-A, Radhakrishnan K, von Figura K, Schmidt B. Molecular basis of multiple sulfatase deficiency, mucolipidosis II/III and Niemann-Pick C1 disease - Lysosomal storage disorders caused by defects of non-lysosomal proteins. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH. 2009;1793(4):710-725.Multiple sulfatase deficiency (MSD), mucolipidosis (MIL) II/III and Niemann-Pick type C1 (NPC1) disease are rare but fatal lysosomal storage disorders caused by the genetic defect of non-lysosomal proteins. The NPC1 protein mainly localizes to late endosomes and is essential for cholesterol redistribution from endocytosed LDL to cellular membranes. NPC1 deficiency leads to lysosomal accumulation of a broad range of lipids. The precise functional mechanism of this membrane protein, however, remains puzzling. ML II, also termed I cell disease. and the less severe ML III result from deficiencies of the Golgi enzyme N-acetylglucosamine 1-phosphotransferase leading to a global defect of lysosome biogenesis. In patient cells, newly synthesized lysosomal proteins are not equipped with the critical lysosomal trafficking marker mannose 6-phosphate, thus escaping from lysosomal sorting at the trans Golgi network. MSD affects the entire sulfatase family, at least seven members of which are lysosomal enzymes that are specifically involved in the degradation of sulfated glycosaminoglycans, sulfolipids or other sulfated molecules. The combined deficiencies of all sulfatases result from a defective post-translational modification by the ER-localized formylglycine-generating enzyme (FGE), which oxidizes a specific cysteine residue to formylglycine, the catalytic residue enabling a unique mechanism of sulfate ester hydrolysis. This review gives an update on the molecular bases of these enigmatic diseases, which have been challenging researchers since many decades and so far led to a number of surprising findings that give deeper insight into both the cell biology and the pathobiochemistry underlying these complex disorders. In case of MSD, considerable progress has been made in recent years towards an understanding of disease-causing FGE mutations. First approaches to link molecular parameters with clinical manifestation have been described and even therapeutical options have been addressed. Further. the discovery of FGE as an essential sulfatase activating enzyme has considerable impact on enzyme replacement or gene therapy of lysosomal storage disorders caused by single sulfatase deficiencies. (C) 2008 Elsevier B.V. All rights reserved
The Future of Canadian Climate Policy — with Marc Lee
No full textMarc Lee is a Senior Economist at the Canadian Centre for Policy Alternatives\u27 BC Office. In addition to tracking federal and provincial budgets and economic trends, Marc has published on a range of topics from poverty and inequality to globalization and international trade to public services and regulation. Marc is the Co-Director of the Climate Justice Project, a research partnership with UBC\u27s School of Community and Regional Planning that examines the links between climate change policies and social justice.Resources:Climate Justice Project: www.policyalternatives.ca/projects/cli…tice-projectMarc Lee\u27s Posts on Policy Note: www.policynote.ca/author/marclee/Canadian Centre for Policy Alternatives: www.policyalternatives.ca/Marc\u27s Twitter: twitter.com/MarcLeeCCPA International Panel on Climate Change, 2021 report: www.ipcc.ch/report/ar6/wg1
Formylglycine Aldehyde Tag-Protein Engineering through a Novel Post-translational Modification
No full textFrese M-A, Dierks T. Formylglycine Aldehyde Tag-Protein Engineering through a Novel Post-translational Modification. CHEMBIOCHEM. 2009;10(3):425-427.Oxidation of a specific cysteine residue to C(alpha)-formylglycine is a novel post-translational modification that is directed by a short recognition motif commonly found in pro- and eukaryotic sulfatases. As recently shown by C. Bertozzi and co-workers, this system can be employed in protein engineering to equip proteins with genetically encoded aldehyde tags for site-specific labeling, conjugation and immobilization
Local Church Week Pastor Andre Mitchell
No full textPastor Andre Mitchell, Pastor, Author, CEO, Deliverance Temple/Andre Mitchell Ministries, Muncie, IN, speaks on how connecting with other believers is important to your faith for Local Church Week
Climate Justice & Inequality: The Future of Canadian Climate Policy — with Marc Lee
No full textMarc Lee is a Senior Economist at the Canadian Centre for Policy Alternatives\u27 BC Office. In addition to tracking federal and provincial budgets and economic trends, Marc has published on a range of topics from poverty and inequality to globalization and international trade to public services and regulation. Marc is the Co-Director of the Climate Justice Project, a research partnership with UBC\u27s School of Community and Regional Planning that examines the links between climate change policies and social justice.Resources: Climate Justice Project: https://www.policyalternatives.ca/projects/climate-justice-projectMarc Lee\u27s Posts on Policy Note: https://www.policynote.ca/author/marclee/Canadian Centre for Policy Alternatives: https://www.policyalternatives.ca/Marc\u27s Twitter: https://twitter.com/MarcLeeCCPA International Panel on Climate Change, 2021 report: https://www.ipcc.ch/report/ar6/wg1
Pearl Andre, Political Activist and Author from Bismarck
No full textAn undated photograph of Pearl Andre, an author and political activist from Bismarck. She wrote the book Women on the Move about the Nonpartisan League in North Dakota in 1975.https://commons.und.edu/nd-politics-photos/1254/thumbnail.jp
UKMARC AMC: Draft Rev 4.0: UK MARC format for archives and manuscripts control (UK MARC AMC)
No full textThis draft is the first attempt to establish a UK MARC specifically for Archives and Manuscripts Control since the British Library indicated that it would countenance such extensions to the national UK MARC format. In order to keep consistency with the general UK MARC format, standard UK MARC subject fields are not included in this document, since they should be taken from the latest version of the UK MARC manual. {A note of them should perhaps be included in UK MARC AMC.} {NB Text in braces is intended to be explanatory material for readers of this draft}. Certain other fields have not been included that might occasionally be used in the cataloguing of archival materials but would generally only be used for such materials in organizations which were combining archive
databases with library databases. This MARC version is intended for use with descriptions of archive or anuscript material that follow, or fit, the traditional style of cataloguing: we assume that these will normally relate
to paper or parchment originals. It is not intended for use with descriptions of other kinds of material. For these, fields may be drawn from the appropriate UK MARC document. MARC versions for use with archives in special formats should be developed, in order to complete the full range of facilities available to archivists and curators
MARC 21 para recursos contínuos
No full textTranslation and adaptation of the MARC 21 Format for Bibliographic Data, and MARC 21 Format for Holdings Data, Network Development and MARC Standards Office, Library of Congress, USA, by Angela Salles. Rio de Janeiro, 2010. 2 v. V.1 MARC 21 format for bibliographic data (updated until October 2010). V.2 MARC 21 format for data collection (Holdings) (updated until October 2008)
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