Linked Life Data

10556300

Source:http://linkedlifedata.com/resource/pubmed/id/10556300

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2000-1-24
pubmed:abstractText
Mutations in the DKC1 gene are responsible for causing the bone marrow failure syndrome, dyskeratosis congenita (DKC; OMIM 305000). The majority of mutations identified to date are missense mutations and are clustered in exons 3, 4 and 11. It is predicted that the corresponding protein dyskerin is a nucleolar phosphoprotein which functions in both pseudo-uridylation and cleavage of precursor rRNA. Dyskerin contains multiple putative nuclear localization signals (NLSs) at the N-terminus (KKHKKKKERKS) and C-terminus [KRKR(X)(17)KKEKKKSKKDKKAK(X)(17)-KKKKKKKKAKEVELVSE]. By fusing dyskerin with the enhanced green fluorescent protein (EGFP) and by following a time course of expression in mammalian cell lines, we showed that full-length dyskerin initially localizes to the nucleoplasm and subsequently accumulates in the nucleoli. A co-localization to the coiled bodies was observed in some cells where dyskerin-EGFP had translocated to the nucleoli. Analysis of a series of mutant constructs indicated that whereas the most C-terminal lysine-rich clusters [KKEKKKS-KKDKKAK(X)(17)KKKKKKKKAKEVELVSE] influence the rate of nucleoplasmic and nucleolar accumulation, the KRKR sequence is primarily responsible for the nuclear import. Nucleolar localization was maintained when either the N- or C-terminal motifs were mutated, but not when all NLSs were removed. We conclude that the intranuclear localization of dyskerin is accomplished by the synergistic effect of a number of NLSs and that the nucleolar localization signals are contained within the NLSs. Further, examination of dyskerin-EGFP fusions mimicking mutations detected in patients indicated that the intracellular mislocalization of dyskerin is unlikely to cause DKC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2515-24
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10556300-3T3 Cells, pubmed-meshheading:10556300-Amino Acid Motifs, pubmed-meshheading:10556300-Amino Acid Sequence, pubmed-meshheading:10556300-Animals, pubmed-meshheading:10556300-Cell Cycle Proteins, pubmed-meshheading:10556300-Cell Nucleolus, pubmed-meshheading:10556300-Cercopithecus aethiops, pubmed-meshheading:10556300-Dyskeratosis Congenita, pubmed-meshheading:10556300-Fluorescent Antibody Technique, pubmed-meshheading:10556300-Green Fluorescent Proteins, pubmed-meshheading:10556300-HeLa Cells, pubmed-meshheading:10556300-Humans, pubmed-meshheading:10556300-Luminescent Proteins, pubmed-meshheading:10556300-Mice, pubmed-meshheading:10556300-Microinjections, pubmed-meshheading:10556300-Molecular Sequence Data, pubmed-meshheading:10556300-Nuclear Proteins, pubmed-meshheading:10556300-Recombinant Fusion Proteins, pubmed-meshheading:10556300-Transfection, pubmed-meshheading:10556300-Vero Cells
pubmed:year
1999
pubmed:articleTitle
Dyskerin localizes to the nucleolus and its mislocalization is unlikely to play a role in the pathogenesis of dyskeratosis congenita.
pubmed:affiliation
Deutsches Krebsforschungszentrum (DKFZ), Department of Molecular Genome Analysis, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't