Linked Life Data

11115844

Source:http://linkedlifedata.com/resource/pubmed/id/11115844

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2001-1-9
pubmed:abstractText
Mutations in MEFV, a gene encoding a protein (marenostrin/pyrin) of unknown function, are associated with familial Mediterranean fever, a genetic condition characterized by febrile episodes of serosal inflammation. Based on its primary structure, this 781 residue protein is thought to function as a nuclear effector molecule. However, recent transient expression studies indicated a perinuclear cytoplasmic localization. Here, we describe the isolation and expression of a novel human MEFV isoform, MEFV-d2, generated by in-frame alternative splicing of exon 2. This transcript, expressed in leukocytes, predicts a 570 residue protein designated marenostrin-d2. To investigate differences in subcellular localization between the full-length protein (marenostrin-fl) and marenostrin-d2, while providing against the overexpression of transiently expressed proteins, we have generated CHO cell lines stably expressing these two isoforms fused to the green fluorescent protein. The localization pattern of marenostrin-d2 differs dramatically from that of marenostrin-fl. Marenostrin-fl is homogeneously distributed over the entire cytoplasm, whereas marenostrin-d2 concentrates into the nucleus. To map the critical domain(s) specifying these differences, deletion mutants have been generated. Deletion of the putative nuclear localization signals (NLS) does not alter the nuclear localization of marenostrin-d2 whereas, despite the lack of discernible NLS in the domain encoded by the exon 1-exon 3 splice junction, deletion of this domain indeed disrupts this localization. These data, which challenge the current domain organization model of marenostrin, strongly suggest that MEFV encodes a nuclear protein and raises the possibility that MEFV alternative splicing may control functions of wild-type and mutant marenostrin proteins by regulating their translocation to the nucleus.
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:day
12
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3001-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11115844-Alternative Splicing, pubmed-meshheading:11115844-Animals, pubmed-meshheading:11115844-Biological Transport, pubmed-meshheading:11115844-Blotting, Northern, pubmed-meshheading:11115844-CHO Cells, pubmed-meshheading:11115844-Cell Nucleus, pubmed-meshheading:11115844-Cricetinae, pubmed-meshheading:11115844-Cytoskeletal Proteins, pubmed-meshheading:11115844-Exons, pubmed-meshheading:11115844-Familial Mediterranean Fever, pubmed-meshheading:11115844-Humans, pubmed-meshheading:11115844-Leukocytes, Mononuclear, pubmed-meshheading:11115844-Mutagenesis, Site-Directed, pubmed-meshheading:11115844-Nuclear Localization Signals, pubmed-meshheading:11115844-Protein Conformation, pubmed-meshheading:11115844-Protein Isoforms, pubmed-meshheading:11115844-Proteins, pubmed-meshheading:11115844-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11115844-Subcellular Fractions
pubmed:year
2000
pubmed:articleTitle
Alternative splicing at the MEFV locus involved in familial Mediterranean fever regulates translocation of the marenostrin/pyrin protein to the nucleus.
pubmed:affiliation
Institut National de la Santé et de la Recherche Médicale (INSERM) U468, Hôpital Henri-Mondor, 51 avenue du Maréchal de-Lattre-de-Tassigny, 94010 Créteil, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't