title: Analysis of epitope-tagged forms of the dyskeratosis congenital protein (dyskerin): identification of a nuclear localization signal.
abstract: The X-linked form of the bone marrow failure syndrome Dyskeratosis congenital is caused by mutations in dyskerin, a 514 amino acid protein that is presumed to play a role in ribosome biogenesis. Here we report that dyskerin tagged with the human immunoglobulin epitope localizes to nuclei of transfected HeLa and COS-1 cells. A carboxyl-terminal domain consisting of amino acids 467-475 and encoding KKEKKKSKK is both necessary and sufficient to mediate nuclear entry. Immunoglobulin-tagged dyskerin did not interact with the Fanconi anemia group A protein, FANCA. These results suggest a nuclear role for dyskerin. Moreover, hematopoietic failure observed in both Dyskeratosis congenital and the most common type of Fanconi anemia is unlikely to have a common mechanism resulting from abnormal physical interactions between the respective gene products of these disorders.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine.Houston. TX 77030, USA. hagopy@bcm.tmc.edu
authors.forename: H
authors.initials: H
authors.lastname: Youssoufian
authors.forename: V
authors.initials: V
authors.lastname: Gharibyan
authors.forename: M
authors.initials: M
authors.lastname: Qatanani
mesh_terms: D000345:Affinity Labels; D000818:Animals; D019556:COS Cells / Q000648:ultrastructure; D018797:Cell Cycle Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D004268:DNA-Binding Proteins; D019871:Dyskeratosis Congenita / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000939:Epitopes / Q000276:immunology / Q000378:metabolism*; D052217:Fanconi Anemia Complementation Group A Protein; D006367:HeLa Cells / Q000648:ultrastructure; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009154:Mutation; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D013347:Subcellular Fractions / Q000737:chemistry; D014162:Transfection
chemical_list: D000345:Affinity Labels; D018797:Cell Cycle Proteins; C112148:DKC1 protein, human; D004268:DNA-Binding Proteins; D000939:Epitopes; C498471:FANCA protein, human; D052217:Fanconi Anemia Complementation Group A Protein; D007074:Immunoglobulin G; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins