Multiple importins function as nuclear transport receptors for the Rev protein of human immunodeficiency virus type 1.
The Rev protein of human immunodeficiency virus type 1 is an RNA-binding protein that is required for nuclear export of unspliced and partially spliced viral mRNAs. Nuclear import of human immunodeficiency virus type 1 Rev has been suggested to depend on the classic nuclear transport receptor importin beta, but not on the adapter protein importin alpha. We now show that, similar to importin alpha, Rev is able to dissociate RanGTP from recycling importin beta, a reaction that leads to the formation of a novel import complex. Besides importin beta, the transport receptors transportin, importin 5, and importin 7 specifically interact with Rev and promote its nuclear import in digitonin-permeabilized cells. A single arginine-rich nuclear localization sequence of Rev is required for interaction with all importins tested so far. In contrast to the importin beta-binding domain of importin alpha, Rev interacts with an N-terminal fragment of importin beta. Transportin contains two independent binding sites for Rev. Hence, the mode of interaction of importin beta and transportin with Rev is clearly distinct from that with their classic import cargoes. Taken together, the viral protein takes advantage of multiple cellular transport pathways for its nuclear accumulation.
Arnold
Marc
M
Universität Heidelberg, Abteilung Virologie, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany; Universität Göttingen, Zentrum für Biochemie und Molekulare Zellbiologie, Humboldtallee 23, 37073 Göttingen, Germany.
Nath
Annegret
A
Universität Göttingen, Zentrum für Biochemie und Molekulare Zellbiologie, Humboldtallee 23, 37073 Göttingen, Germany.
Hauber
Joachim
J
Heinrich Pette Institute for Experimental Virology and Immunology, Martinistrasse 52, 20251 Hamburg, Germany.
Kehlenbach
Ralph H
RH
Universität Heidelberg, Abteilung Virologie, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany; Universität Göttingen, Zentrum für Biochemie und Molekulare Zellbiologie, Humboldtallee 23, 37073 Göttingen, Germany. Electronic address: rkehlen@gwdg.de.
D021581:Active Transport, Cell Nucleus; D001665:Binding Sites; D015694:Gene Products, rev / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000502:physiology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012367:RNA, Viral / Q000737:chemistry; D015533:Transcriptional Activation; D028901:alpha Karyopherins / Q000378:metabolism; D028961:beta Karyopherins / Q000502:physiology; D020931:ran GTP-Binding Protein / Q000737:chemistry
D015694:Gene Products, rev; C423142:KPNA1 protein, human; C494630:KPNA6 protein, human; D028884:Karyopherins; D012367:RNA, Viral; D028901:alpha Karyopherins; D028961:beta Karyopherins; D020931:ran GTP-Binding Protein