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.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Affinity Labels*
-
Animals
-
COS Cells / ultrastructure
-
Cell Cycle Proteins / genetics
-
Cell Cycle Proteins / immunology*
-
Cell Cycle Proteins / metabolism*
-
DNA-Binding Proteins*
-
Dyskeratosis Congenita / genetics
-
Dyskeratosis Congenita / immunology
-
Dyskeratosis Congenita / metabolism
-
Epitopes / immunology
-
Epitopes / metabolism*
-
Fanconi Anemia Complementation Group A Protein
-
HeLa Cells / ultrastructure
-
Humans
-
Immunoglobulin G / immunology
-
Immunoglobulin G / metabolism
-
Microscopy, Fluorescence
-
Mutation
-
Nuclear Localization Signals
-
Nuclear Proteins / genetics
-
Nuclear Proteins / immunology*
-
Nuclear Proteins / metabolism*
-
Protein Binding
-
Proteins / metabolism
-
Recombinant Fusion Proteins / biosynthesis
-
Recombinant Fusion Proteins / immunology
-
Recombinant Fusion Proteins / metabolism
-
Subcellular Fractions / chemistry
-
Transfection
Substances
-
Affinity Labels
-
Cell Cycle Proteins
-
DKC1 protein, human
-
DNA-Binding Proteins
-
Epitopes
-
FANCA protein, human
-
Fanconi Anemia Complementation Group A Protein
-
Immunoglobulin G
-
Nuclear Localization Signals
-
Nuclear Proteins
-
Proteins
-
Recombinant Fusion Proteins