title: A leptomycin B-sensitive homologue of human CRM1 promotes nuclear export of nuclear export sequence-containing proteins in Drosophila cells.
abstract: The Rev protein of human immunodeficiency virus is a nuclear shuttling protein that promotes nuclear export of mRNAs that encode the viral structural proteins Gag, Pol, and Env. Rev binds to a highly structured RNA motif, the Rev-responsive element (RRE), that is present in all Rev-responsive viral transcripts and facilitates their entry into a nuclear export pathway by recruiting cellular export factors. In mammalian and yeast cells, the principal export receptor engaged by Rev has been identified as the importin/transportin family member CRM1/exportin 1. CRM1 binds directly to a leucine-rich nuclear export sequence (NES) present in Rev, and similar motifs have been identified in a variety of cellular nuclear shuttling proteins. We and our colleagues previously demonstrated that, in transfected Drosophila cells, HIV-1 Rev is fully functional and promotes expression of the viral envelope glycoprotein. We now demonstrate that the fundamental mechanism of Rev action in insect cells is identical to that observed in the mammalian systems. In particular, we show that Drosophila cells express a leptomycin B-sensitive homologue of human CRM1 that supports Rev-dependent gene expression and is required for nuclear export of NES-containing proteins in insect cells.
authors.affiliation: The Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, DD1 9SY, Scotland.
authors.forename: M B
authors.initials: MB
authors.lastname: Fasken
authors.forename: R
authors.initials: R
authors.lastname: Saunders
authors.forename: M
authors.initials: M
authors.lastname: Rosenberg
authors.forename: D W
authors.initials: DW
authors.lastname: Brighty
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D004330:Drosophila / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D015967:Gene Expression Regulation, Viral; D015694:Gene Products, rev / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D019302:HIV Envelope Protein gp160 / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000378:metabolism; D010957:Plasmids; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism; D054321:rev Gene Products, Human Immunodeficiency Virus; D000097606:Exportin 1 Protein
chemical_list: D000903:Antibiotics, Antineoplastic; D002352:Carrier Proteins; D018076:DNA, Complementary; D005231:Fatty Acids, Unsaturated; D015694:Gene Products, rev; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D028884:Karyopherins; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014759:Viral Envelope Proteins; D054321:rev Gene Products, Human Immunodeficiency Virus; D000097606:Exportin 1 Protein; C038753:leptomycin B