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The Specificity of the CRM1-Rev Nuclear Export Signal Interaction Is Mediated by RanGTP

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Askjaer, Peter, Jensen, Torben Heick, Nilsson, Jakob, Englmeier, Ludwig, Kjems, Jørgen·1998·Journal of Biological Chemistry

DOI 10.1074/jbc.273.50.33414

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Abstract

Nuclear export of intron-containing human immunodeficiency virus type 1 (HIV-1) RNA is mediated by the viral Rev protein that contains both an RNA binding domain specific for the viral Rev response element (RRE) and a nuclear export signal (NES). The cellular CRM1 (Exportin1) protein functions as a nuclear export receptor for proteins carrying a Rev-like NES in a process that also requires the GTP bound form of the Ran GTPase. Using purified recombinant factors, we show by co-precipitation, gel mobility shift and protein footprinting assays that full-length Rev protein interacts directly with CRM1 in vitro independently of both the integrity of the characteristic leucine residues of the NES and the presence of the cytotoxin leptomycin B (LMB). Addition of RanGTP induces the formation of an RRE-Rev-CRM1-RanGTP complex that is sensitive to LMB, NES mutations, and Ran being charged with GTP. Within this complex, CRM1 is readily cross-linked to Cys89 near the NES of Rev. By protein footprinting, we demonstrate that the NES of Rev and two regions in CRM1 become inaccessible to endoproteinases upon binding suggesting that these regions are involved in protein-protein interactions. Our data are consistent with a model in which CRM1 is the nuclear export receptor for the Rev-RRE ribonucleoprotein complex and that RanGTP binds to a preformed Rev-CRM1 complex and specifies a functional interaction with the NES.

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See all 219

Authors: Askjaer, P., Jensen, T. H., Nilsson, J., Englmeier, L., & Kjems, J.
Affiliations: Aarhus University (DK)
Corresponding author: Kjems, Jørgen
ORCID: Askjaer, Peter
Jensen, Torben Heick
Nilsson, Jakob
Englmeier, Ludwig
Kjems, Jørgen
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 1998-12
Volume: 273
Issue: 50
Pages: 33414-33422
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.273.50.33414
OpenAlex: W1979451022
Cited by: 219
References: 49
Citations by year: 2026: 2 · 2025: 3 · 2024: 6 · 2023: 2 · 2022: 7 · 2021: 3 · 2020: 7 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 6 · 2015: 5 · 2014: 10 · 2013: 8 · 2012: 16
FWCI: 4.83
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 7979 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: Kræftens Bekæmpelse
Karen Elise Jensens Fond
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords: CRM1, Rev protein, nuclear export signal, Ran GTPase, Rev response element, protein-protein interaction, leptomycin B, nuclear export receptor
MeSH terms: Exportin 1 Protein, Base Sequence, Carrier Proteins, Cell Nucleus, Guanosine Triphosphate, Recombinant Proteins, Ultraviolet Rays, Signal Transduction, Gene Products, rev, DNA Primers, Receptors, Cytoplasmic and Nuclear, Karyopherins

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The Specificity of the CRM1-Rev Nuclear Export Signal Interaction Is Mediated by RanGTP

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