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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
14
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pubmed:dateCreated |
2005-7-4
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pubmed:abstractText |
The hepatitis C virus (HCV) replication complex is localized within detergent-resistant membranes or lipid rafts. We analyzed the protein contents of detergent-resistant fractions isolated from Huh7 cells expressing a self-replicating full-length HCV-1b genome. Using two-dimensional gel electrophoresis followed by mass spectrometry, we identified N-Ras as one of the proteins in which expression was increased in the detergent-resistant fractions from HCV genomic replicon clones compared to control cells. N-Ras is an activator of the phosphatidylinositol-3-kinase (PI3K)-Akt pathway. We found that the activities of PI3K and Akt, as well as the activity of their downstream target, mTOR, in the HCV-replicating cells were increased. Both PI3K-Akt- and mTOR-dependent pathways have been shown to promote cell survival. In agreement with this, HCV replicon cells were resistant to serum starvation-induced apoptosis. We also characterized the role of this pathway in HCV replication. Reduction of N-Ras expression by transfection of N-Ras small interfering RNA (siRNA) resulted in increased replication of HCV. We observed a similar increase in HCV replication in cells treated with the PI3K inhibitor LY294002 and in cells transfected with mTOR siRNA. Taken together, these data suggest that increased N-Ras levels in subcellular sites of HCV replication and stimulation of the prosurvival PI3K-Akt pathway and mTOR by HCV not only protect cells against apoptosis but also contribute to the maintenance of steady-state levels of HCV replication. These effects may contribute to the establishment of persistent infection by HCV.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-10390360,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-11110665,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-11152498,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-11278872,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-11413487,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-11907240,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-11943782,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-11956073,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-11994280,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-12033786,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-12186904,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-12230468,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-12446712,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-12527380,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-12634374,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-12655075,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-12692249,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-12876558,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-12951042,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-14580340,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-14663478,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-14675631,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-14709551,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-14999271,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-15016873,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-15030566,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-15094774,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-15193258,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-15207630,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-15209377,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-15298170,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-15308747,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-15314020,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-15326295,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-15351205,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-15361852,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-15367622,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-15542681,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-8052307,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-8599949,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15994768-9525648
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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/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/MTOR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/TOR Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-538X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
79
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8742-9
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pubmed:dateRevised |
2011-1-7
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pubmed:meshHeading |
pubmed-meshheading:15994768-Apoptosis,
pubmed-meshheading:15994768-Cell Line, Tumor,
pubmed-meshheading:15994768-Hepacivirus,
pubmed-meshheading:15994768-Humans,
pubmed-meshheading:15994768-Membrane Microdomains,
pubmed-meshheading:15994768-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:15994768-Protein Kinases,
pubmed-meshheading:15994768-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15994768-Proto-Oncogene Proteins,
pubmed-meshheading:15994768-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:15994768-Signal Transduction,
pubmed-meshheading:15994768-TOR Serine-Threonine Kinases,
pubmed-meshheading:15994768-Virus Replication,
pubmed-meshheading:15994768-ras Proteins
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pubmed:year |
2005
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pubmed:articleTitle |
Activation of the N-Ras-PI3K-Akt-mTOR pathway by hepatitis C virus: control of cell survival and viral replication.
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pubmed:affiliation |
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. North, M5-A864, Box 19024, Seattle, WA 98109-1024, USA.
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pubmed:publicationType |
Journal Article
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