Alterations in HIV-1 Rev transport in response to cell stress.
Movement of HIV-1 Rev between the nucleus and cytoplasm is essential to its function. While normally nuclear, the protein can be induced to accumulate in the cytoplasm upon inhibition of RNA polymerase I/II. Nuclear accumulation of Rev in the presence of these inhibitors was found to be rescued upon addition of leptomycin B, an inhibitor of Rev nuclear export. This finding, in conjunction with kinetic data on nuclear import, indicates that the effect of the RNA polymerase inhibitors is due to an inversion of the rates of nuclear import versus export possibly achieved by increasing the rate of Rev nuclear export. We also examined whether changes in Rev localization could be due to a stress response. While neither ultraviolet radiation nor heat shock affected Rev subcellular localization, both oxidative and osmotic shocks induce changes in Rev localization comparable to that observed with the RNA polymerase inhibitors. The ability of certain serine/threonine kinase inhibitors, including CKI/II inhibitors, to cause cytoplasmic accumulation of Rev suggested that the alteration in Rev distribution could be due to changes in Rev or CRM1 phosphorylation. However, no change in extent of phosphorylation of either protein is observed upon treatment of cells with any of the agents tested, indicating involvement of another cellular factor.
Soros
V
V
Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Cochrane
A
A
D021581:Active Transport, Cell Nucleus; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D015694:Gene Products, rev / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins; D009997:Osmotic Pressure; D018384:Oxidative Stress; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D012318:RNA Polymerase I / Q000037:antagonists & inhibitors; D012319:RNA Polymerase II / Q000037:antagonists & inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013347:Subcellular Fractions; D054321:rev Gene Products, Human Immunodeficiency Virus; D000097606:Exportin 1 Protein
D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D015694:Gene Products, rev; D028884:Karyopherins; D010749:Phosphoprotein Phosphatases; D047428:Protein Kinase Inhibitors; D012318:RNA Polymerase I; D012319:RNA Polymerase II; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D054321:rev Gene Products, Human Immunodeficiency Virus; D000097606:Exportin 1 Protein; C038753:leptomycin B