Source:http://linkedlifedata.com/resource/pubmed/id/19717177
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2009-10-19
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pubmed:abstractText |
The human APOBEC3G (A3G) is a potent inhibitor of HIV-1 replication and its activity is suppressed by HIV-1 virion infectivity factor (Vif). Vif neutralizes A3G mainly by inducing its degradation in the proteasome and blocking its incorporation into HIV-1 virions. Assessing the time needed for A3G incorporation into virions is, therefore, important to determine how quickly Vif must act to induce its degradation. We show that modelling the intracellular half-life of A3G can induce its Vif-independent targeting to the ubiquitin-proteasome system. By using various amino acids (X) in a cleavable ubiquitin-X-A3G fusion, we demonstrate that the half-life (t1/2) of X-A3G can be manipulated. We show that A3G molecules with a half-life of 13 min are incorporated into virions, whereas those with a half-life shorter than 5 min were not. The amount of X-A3G incorporated into virions increases from 13 min (Phe-A3G) to 85 min (Asn-A3G) and remains constant after this time period. Interestingly, despite the presence of similar levels of Arg-A3G (t1/2=28 min) and Asp-A3G (t1/2=65 min) into HIV-1 Deltavif virions, inhibition of viral infectivity was only evident in the presence of A3G proteins with a longer half-life (t1/2 > or = 65 min).
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/APOBEC3G protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cytidine Deaminase,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/vif Gene Products, Human...,
http://linkedlifedata.com/resource/pubmed/chemical/vif protein, Human...
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1096-0341
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
25
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pubmed:volume |
393
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
286-94
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pubmed:meshHeading |
pubmed-meshheading:19717177-Cell Line,
pubmed-meshheading:19717177-Cytidine Deaminase,
pubmed-meshheading:19717177-HIV Infections,
pubmed-meshheading:19717177-HIV-1,
pubmed-meshheading:19717177-Half-Life,
pubmed-meshheading:19717177-Humans,
pubmed-meshheading:19717177-Ubiquitin,
pubmed-meshheading:19717177-Virus Replication,
pubmed-meshheading:19717177-vif Gene Products, Human Immunodeficiency Virus
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pubmed:year |
2009
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pubmed:articleTitle |
Ubiquitin-fusion as a strategy to modulate protein half-life: A3G antiviral activity revisited.
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pubmed:affiliation |
URIA-Centro Patogénese Molecular, Faculdade de Farmácia da Universidade Lisboa, Lisboa 1649-059, Portugal.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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