Functional dissection of the HIV-1 Rev trans-activator--derivation of a trans-dominant repressor of Rev function. NLM AIDSLINE Important note: Information in this article was accurate in 1989. The state of the art may have changed since the publication date.

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Functional dissection of the HIV-1 Rev trans-activator--derivation of a trans-dominant repressor of Rev function.

Cell. 1989 Jul 14;58(1):205-14. Unique Identifier : AIDSLINE MED/89324054
Malim MH; Bohnlein S; Hauber J; Cullen BR; Howard Hughes Medical Institute, Duke University Medical Center,; Durham, North Carolina 27710.

Abstract: Human immunodeficiency virus type 1 (HIV-1) encodes a nuclear trans-activator, termed Rev, that is required for the expression of the viral structural proteins and, hence, for viral replication. The Rev protein acts posttranscriptionally to induce the sequence-specific nuclear export of unspliced HIV-1 mRNA species that are otherwise excluded from the cell cytoplasm. We have used site-directed mutagenesis to identify two distinct regions of the HIV-1 Rev protein that are required for in vivo biological activity. The larger and more N-terminal of these two regions includes, but extends beyond, an arginine-rich sequence element required for nuclear localization. Mutation of a second, more C-terminal Rev protein sequence element was found to yield defective Rev proteins that act as trans-dominant inhibitors of Rev function. These Rev mutants are shown to inhibit HIV-1 replication when expressed in transfected cells and may have potential application in the treatment of HIV-1 related disease.
Keywords: Amino Acid Sequence Animal Cells, Cultured Cercopithecus aethiops DNA Mutational Analysis Gene Expression Regulation HIV/*GENETICS Molecular Sequence Data Nuclear Proteins/PHYSIOLOGY Phosphoproteins/PHYSIOLOGY Phosphorylation Precipitin Tests Repressor Proteins/PHYSIOLOGY Retroviridae Proteins/*PHYSIOLOGY Structure-Activity Relationship Transcription Factors/*PHYSIOLOGY Transcription, Genetic JOURNAL ARTICLE

KWDaminoacidsequenceanimalcells,culturedcercopithecusaethiopsdnamutationalanalysisgeneexpressionregulationhiv/KWDgeneticsmolecularsequencedatanuclearproteins/physiologyphosphoproteins/physiologyphosphorylationprecipitintestsrepressorproteins/physiologyretroviridaeproteins/KWDphysiologystructure-activityrelationshiptranscriptionfactors/KWDphysiologytranscription,geneticjournalarticle
891130
M89B0524

Copyright © 1989 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

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