Linked Life Data

15475359

Source:http://linkedlifedata.com/resource/pubmed/id/15475359

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
53
pubmed:dateCreated
2004-12-23
pubmed:abstractText
The transcriptional coactivator lens epithelium-derived growth factor (LEDGF)/p75 acts as a chromatin tethering factor for human immunodeficiency virus type 1 (HIV-1) integrase protein, determining its nuclear localization and its tight association with nuclear DNA. Here we identify a second function for the LEDGF/p75-integrase interaction. We observed that stable introduction of HIV-1 integrase (IN) transcription units into cells made stringently LEDGF/p75-deficient by RNAi resulted in much lower steady state levels of IN protein than introduction into LEDGF/p75 wild type cells. The same LEDGF/p75-dependent disparity was observed for feline immunodeficiency virus IN. However, IN mRNA levels were equivalent in the presence and absence of LEDGF/p75. A post-translational mechanism was confirmed when the half-life of HIV-1 IN protein was found to be much shorter in LEDGF/p75-deficient cells. Proteasome inhibition fully countered this extreme instability, increasing IN protein levels to those seen in LEDGF/p75 wild type cells and implicating proteasomal destruction as the main cause of IN instability. Consistent with these data, increased ubiquitinated HIV-1 IN was found in the LEDGF/p75 knock-down cells. Moreover, restoration of LEDGF/p75 to knocked down clones rescued HIV-1 IN stability. Subcellular fractionation showed that HIV-1 IN is exclusively cytoplasmic in LEDGF/p75-deficient cells, but mainly nuclear in LEDGF/p75 wild type cells, and that cytoplasmic HIV-1 IN has a shorter half-life than nuclear HIV-1 IN. However, using LEDGF proteins defective for nuclear localization and IN interaction, we further determined that protection of HIV-1 IN from the proteasome requires neither chromatin tethering nor nuclear residence. Protection requires only interaction with LEDGF/p75, and it is independent of the subcellular localization of the IN-LEDGF complex.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
31
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
55570-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15475359-Blotting, Western, pubmed-meshheading:15475359-Cell Line, pubmed-meshheading:15475359-Cell Nucleus, pubmed-meshheading:15475359-Chromatin, pubmed-meshheading:15475359-Cytoplasm, pubmed-meshheading:15475359-DNA, pubmed-meshheading:15475359-DNA, Complementary, pubmed-meshheading:15475359-HIV Integrase, pubmed-meshheading:15475359-Humans, pubmed-meshheading:15475359-Immunoblotting, pubmed-meshheading:15475359-Immunoprecipitation, pubmed-meshheading:15475359-Integrases, pubmed-meshheading:15475359-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:15475359-Lentivirus, pubmed-meshheading:15475359-Microscopy, Confocal, pubmed-meshheading:15475359-Microscopy, Fluorescence, pubmed-meshheading:15475359-Plasmids, pubmed-meshheading:15475359-Promoter Regions, Genetic, pubmed-meshheading:15475359-Protease Inhibitors, pubmed-meshheading:15475359-Proteasome Endopeptidase Complex, pubmed-meshheading:15475359-Protein Processing, Post-Translational, pubmed-meshheading:15475359-RNA, Messenger, pubmed-meshheading:15475359-RNA Interference, pubmed-meshheading:15475359-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15475359-Transfection, pubmed-meshheading:15475359-Ubiquitin
pubmed:year
2004
pubmed:articleTitle
Lens epithelium-derived growth factor/p75 prevents proteasomal degradation of HIV-1 integrase.
pubmed:affiliation
Molecular Medicine Program and Department of Immunology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
pubmed:publicationType
Journal Article