Abstract
The HIV-1 Rev protein facilitates the nuclear export of mRNA containing the Rev response element (RRE) through binding to the export receptor CRM-1. Here we show that a cellular nuclear protein, Sam68 (Src-associated protein in mitosis), specifically interacts with RRE and can partially substitute for as well as synergize with Rev in RRE-mediated gene expression and virus replication. Differential sensitivity to leptomycin B, an inhibitor of CRM-1, indicates that the export pathways mediated by Rev and Sam68 are distinct. C-terminally deleted mutants of Sam68 inhibited the transactivation of RRE-mediated expression by both wild-type Sam68 and Rev. They were retained in the cytoplasm and impeded the nuclear localization of Rev in co-expressed cells. These mutants also inhibited wild-type HIV-1 replication to the same extent as the RevM10 mutant, and may be useful as anti-viral agents in the treatment of AIDS.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Antibodies / metabolism
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Carrier Proteins / antagonists & inhibitors
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Carrier Proteins / metabolism
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Cells, Cultured / virology
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Chloramphenicol O-Acetyltransferase / genetics
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Cytoplasm / metabolism
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DNA-Binding Proteins
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Enzyme Inhibitors / pharmacology
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Exportin 1 Protein
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Fatty Acids, Unsaturated / pharmacology
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Gene Expression Regulation, Viral
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Gene Products, rev*
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Genes, Dominant
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Genes, Reporter
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HIV-1 / physiology*
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HeLa Cells / virology
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Humans
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Karyopherins*
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Kinetin
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Mutation
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Purines / pharmacology
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RNA-Binding Proteins / antagonists & inhibitors
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RNA-Binding Proteins / genetics*
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RNA-Binding Proteins / metabolism*
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Receptors, Cytoplasmic and Nuclear*
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Response Elements
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Virus Replication / genetics*
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rev Gene Products, Human Immunodeficiency Virus
Substances
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Adaptor Proteins, Signal Transducing
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Antibodies
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Carrier Proteins
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DNA-Binding Proteins
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Enzyme Inhibitors
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Fatty Acids, Unsaturated
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Gene Products, rev
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KHDRBS1 protein, human
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Karyopherins
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Purines
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RNA-Binding Proteins
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Receptors, Cytoplasmic and Nuclear
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rev Gene Products, Human Immunodeficiency Virus
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olomoucine
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Chloramphenicol O-Acetyltransferase
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Kinetin
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leptomycin B