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Prepublished online as a Blood First Edition Paper on February 13, 2003; DOI 10.1182/blood-2002-12-3878. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-12-3878v1 101/12/5039    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Da Costa, L. Articles by Mohandas, N. Search for Related Content PubMed PubMed Citation Articles by Da Costa, L. Articles by Mohandas, N. Related Collections Hematopoiesis and Stem Cells Red Cells Gene Expression Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 June 2003, Vol. 101, No. 12, pp. 5039-5045 RED CELLS Nucleolar localization of RPS19 protein in normal cells and mislocalization due to mutations in the nucleolar localization signals in 2 Diamond-Blackfan anemia patients: potential insights into pathophysiology Lydie Da Costa, Gil Tchernia, Philippe Gascard, Annie Lo, Joerg Meerpohl, Charlotte Niemeyer, Joel-Anne Chasis, Jason Fixler, and Narla Mohandas From the Laboratoire d'Hématologie, Assistance Publique des Hôpitaux de Paris (AP-HP), Faculté deMédecine Paris XI, Institut National de la Santé etde la Recherche Médicale (INSERM) U473, Hôpital de Bicêtre, Le Kremlin Bicêtre, France; the Lawrence Berkeley National Laboratory, Berkeley, CA; the Universitäts-Kinderklinik, Freiburg, Germany; and the New York Blood Center, New York, NY. Ribosomal protein S19 (RPS19) is frequently mutated in Diamond-Blackfan anemia (DBA), a rare congenital hypoplastic anemia. Recent studies have shown that RPS19 expression decreases during terminal erythroid differentiation. Currently no information is available on the subcellular localization of normal RPS19 and the potential effects of various RPS19 mutations on cellular localization. In the present study, using wild-type and mutant RPS19 cDNA, we explored the subcellular distribution of normal and mutant proteins in a fibroblast cell line (Cos-7 cells). RPS19 was detected primarily in the nucleus, and more specifically in the nucleoli, where RPS19 colocalized with the nucleolar protein nucleolin. Using various N-terminal and C-terminal deletion constructs, we identified 2 nucleolar localization signals (NoSs) in RPS19: the first comprising amino acids Met1 to Arg16 in the NH2-terminus and the second comprising Gly120 to Asn142 in the COOH-terminus. Importantly, 2 mutations identified in DBA patients, Val15Phe and Gly127Gln, each of which localized to 1 of the 2 NoS, failed to localize RPS19 to the nucleolus. In addition to their mislocalization, there was a dramatic decrease in the expression of the 2 mutant proteins compared to the wild type. This decrease in protein expression was specific for the mutant RPS19, since expression of other proteins was normal. The present findings enable us to document the nucleolar localization signals in RPS19 and help define the phenotypic consequences of some mutations in RPS19 in DBA. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Diamond-Blackfan anemia and nucleolar transport Alan D. D'Andrea Blood 2003 101: 4650-4651. [Full Text] [PDF] This article has been cited by other articles: A.-M. Filip, J. Klug, S. Cayli, S. Frohlich, T. Henke, P. Lacher, R. Eickhoff, P. Bulau, M. Linder, C. Carlsson-Skwirut, et al. Ribosomal Protein S19 Interacts with Macrophage Migration Inhibitory Factor and Attenuates Its Pro-inflammatory Function J. Biol. Chem., March 20, 2009; 284(12): 7977 - 7985. [Abstract] [Full Text] [PDF] A. Cretien, C. Hurtaud, H. Moniz, A. Proust, I. Marie, O. Wagner-Ballon, V. Choesmel, P.-E. Gleizes, T. Leblanc, J. Delaunay, et al. Study of the effects of proteasome inhibitors on ribosomal protein S19 (RPS19) mutants, identified in patients with Diamond-Blackfan anemia Haematologica, November 1, 2008; 93(11): 1627 - 1634. [Abstract] [Full Text] [PDF] S. Kundu-Michalik, M.-A. Bisotti, E. Lipsius, A. Bauche, A. Kruppa, T. Klokow, G. Kammler, and J. Kruppa Nucleolar Binding Sequences of the Ribosomal Protein S6e Family Reside in Evolutionary Highly Conserved Peptide Clusters Mol. Biol. Evol., March 1, 2008; 25(3): 580 - 590. [Abstract] [Full Text] [PDF] L. A. Gregory, A.-H. Aguissa-Toure, N. Pinaud, P. Legrand, P.-E. Gleizes, and S. Fribourg Molecular basis of Diamond Blackfan anemia: structure and function analysis of RPS19 Nucleic Acids Res., September 27, 2007; 35(17): 5913 - 5921. [Abstract] [Full Text] [PDF] M. Angelini, S. Cannata, V. Mercaldo, L. Gibello, C. Santoro, I. Dianzani, and F. Loreni Missense mutations associated with Diamond-Blackfan anemia affect the assembly of ribosomal protein S19 into the ribosome Hum. Mol. Genet., July 15, 2007; 16(14): 1720 - 1727. [Abstract] [Full Text] [PDF] J. Flygare and S. Karlsson Diamond-Blackfan anemia: erythropoiesis lost in translation Blood, April 15, 2007; 109(8): 3152 - 3154. [Abstract] [Full Text] [PDF] S. Orru, A. Aspesi, M. Armiraglio, M. Caterino, F. Loreni, M. Ruoppolo, C. Santoro, and I. Dianzani Analysis of the Ribosomal Protein S19 Interactome Mol. Cell. Proteomics, March 1, 2007; 6(3): 382 - 393. [Abstract] [Full Text] [PDF] V. Choesmel, D. Bacqueville, J. Rouquette, J. Noaillac-Depeyre, S. Fribourg, A. Cretien, T. Leblanc, G. Tchernia, L. Da Costa, and P.-E. Gleizes Impaired ribosome biogenesis in Diamond-Blackfan anemia Blood, February 1, 2007; 109(3): 1275 - 1283. [Abstract] [Full Text] [PDF] K. M. Austin, R. J. Leary, and A. Shimamura The Shwachman-Diamond SBDS protein localizes to the nucleolus Blood, August 15, 2005; 106(4): 1253 - 1258. [Abstract] [Full Text] [PDF]

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