Nucleoporins nup98 and nup214 participate in nuclear export of human immunodeficiency virus type 1 Rev.
Human immunodeficiency virus type 1 (HIV-1) Rev contains a leucine-rich nuclear export signal that is essential for its nucleocytoplasmic export mediated by hCRM1. We examined the role of selected nucleoporins, which are located in peripheral structures of the nuclear pore complex and are thought to be involved in export, in Rev function in human cells. First, we found that upon actinomycin D treatment, Nup98, but not Nup214 or Nup153, is able to translocate to the cytoplasm of HeLa cells, demonstrating that Nup98 may act as a soluble factor. We further showed that Rev can recruit Nup98 and Nup214, but not Nup153, to the nucleolus. We also found that the isolated FG-containing repeat domains of Nup98 and Nup214, but not those of Nup153, competitively inhibit the Rev/RRE-mediated expression of HIV. Taken together, the recruitment of Nup98 and Nup214 by Rev and the competitive inhibition exhibited by their NP domains demonstrate direct participation of Nup98 and Nup214 in the Rev-hCRM1-mediated export.
Zolotukhin
A S
AS
Human Retrovirus Pathogenesis Group, ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA.
Felber
B K
BK
D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000502:physiology*; D002466:Cell Nucleolus / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology; D015694:Gene Products, rev / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear; D020449:Repetitive Sequences, Amino Acid; D014981:Xenopus; D054321:rev Gene Products, Human Immunodeficiency Virus; D000097606:Exportin 1 Protein
D002352:Carrier Proteins; D003609:Dactinomycin; D015694:Gene Products, rev; D028884:Karyopherins; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D054321:rev Gene Products, Human Immunodeficiency Virus; D000097606:Exportin 1 Protein; C079377:NUP153 protein, human