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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
32
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pubmed:dateCreated |
2004-8-2
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pubmed:abstractText |
Human lens epithelium-derived growth factor (LEDGF)/p75 protein forms a specific nuclear complex with human immunodeficiency virus type 1 (HIV-1) integrase and is essential for nuclear localization and chromosomal association of the viral protein. We now studied nuclear import of LEDGF/p75 in live and semipermeabilized cells. We show that nuclear import of LEDGF/p75 is GTP-, Ran-, importin-alpha/beta-, and energy-dependent and that the protein competes with the canonical SV40 large T antigen nuclear localization signal (NLS) for nuclear import receptors. We identified the NLS of LEDGF/p75 through deletion analysis and site-directed mutagenesis. The LEDGF/p75 NLS, 148GRKRKAEKQ156, belongs to the canonical SV40-like family. Fusion of this short peptide to the amino terminus of Escherichia coli beta-galactosidase rendered the fusion protein nuclear, confirming that the LEDGF/p75 NLS is transferable. Moreover, a single amino acid change in the NLS was sufficient to exclude the mutant LEDGF/p75 protein from the nucleus and abolish nuclear import of HIV-1 integrase.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Polyomavirus Transforming,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorescent Dyes,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Guanosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/HIV Integrase,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Luminescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Localization Signals,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RAN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/alpha Karyopherins,
http://linkedlifedata.com/resource/pubmed/chemical/beta Karyopherins,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Galactosidase,
http://linkedlifedata.com/resource/pubmed/chemical/lens epithelium-derived growth...,
http://linkedlifedata.com/resource/pubmed/chemical/ran GTP-Binding Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
33421-9
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15163664-Alternative Splicing,
pubmed-meshheading:15163664-Amino Acid Sequence,
pubmed-meshheading:15163664-Antigens, Polyomavirus Transforming,
pubmed-meshheading:15163664-Binding, Competitive,
pubmed-meshheading:15163664-Biological Transport, Active,
pubmed-meshheading:15163664-Cell Nucleus,
pubmed-meshheading:15163664-Escherichia coli,
pubmed-meshheading:15163664-Fluorescent Dyes,
pubmed-meshheading:15163664-Gene Deletion,
pubmed-meshheading:15163664-Glutathione Transferase,
pubmed-meshheading:15163664-Green Fluorescent Proteins,
pubmed-meshheading:15163664-Guanosine Triphosphate,
pubmed-meshheading:15163664-HIV Integrase,
pubmed-meshheading:15163664-HeLa Cells,
pubmed-meshheading:15163664-Humans,
pubmed-meshheading:15163664-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:15163664-Luminescent Proteins,
pubmed-meshheading:15163664-Mutagenesis, Site-Directed,
pubmed-meshheading:15163664-Nuclear Localization Signals,
pubmed-meshheading:15163664-Nuclear Proteins,
pubmed-meshheading:15163664-Recombinant Fusion Proteins,
pubmed-meshheading:15163664-Signal Transduction,
pubmed-meshheading:15163664-Structure-Activity Relationship,
pubmed-meshheading:15163664-Transfection,
pubmed-meshheading:15163664-alpha Karyopherins,
pubmed-meshheading:15163664-beta Karyopherins,
pubmed-meshheading:15163664-beta-Galactosidase,
pubmed-meshheading:15163664-ran GTP-Binding Protein
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pubmed:year |
2004
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pubmed:articleTitle |
Identification and characterization of a functional nuclear localization signal in the HIV-1 integrase interactor LEDGF/p75.
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pubmed:affiliation |
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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