CRM1 is an export receptor for leucine-rich nuclear export signals.
CRM1 is distantly related to receptors that mediate nuclear protein import and was previously shown to interact with the nuclear pore complex. Overexpression of CRM1 in Xenopus oocytes stimulates Rev and U snRNA export from the nucleus. Conversely, leptomycin B, a cytotoxin that is shown to bind to CRM1 protein, specifically inhibits the nuclear export of Rev and U snRNAs. In vitro, CRM1 forms a leptomycin B-sensitive complex involving cooperative binding of both RanGTP and the nuclear export signal (NES) from either the Rev or PKI proteins. We conclude that CRM1 is an export receptor for leucine-rich nuclear export signals and discuss a model for the role of RanGTP in CRM1 function and in nuclear export in general.
Fornerod
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M
European Molecular Biology Laboratory, Heidelberg, Germany.
Ohno
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M
Yoshida
M
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Mattaj
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IW
D000818:Animals; D000935:Antifungal Agents / Q000378:metabolism / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism / Q000494:pharmacology; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D015694:Gene Products, rev / Q000378:metabolism; D028884:Karyopherins; D007930:Leucine / Q000032:analysis; D009687:Nuclear Proteins / Q000378:metabolism; D009865:Oocytes / Q000502:physiology; D021382:Protein Sorting Signals / Q000187:drug effects / Q000502:physiology*; D012342:RNA, Small Nuclear / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors / Q000378:metabolism; D014981:Xenopus; D020931:ran GTP-Binding Protein; D000097606:Exportin 1 Protein
D000935:Antifungal Agents; D002352:Carrier Proteins; D005231:Fatty Acids, Unsaturated; D005656:Fungal Proteins; D019204:GTP-Binding Proteins; D015694:Gene Products, rev; D028884:Karyopherins; D007930:Leucine; D009687:Nuclear Proteins; D021382:Protein Sorting Signals; D012342:RNA, Small Nuclear; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D020931:ran GTP-Binding Protein; D000097606:Exportin 1 Protein; C038753:leptomycin B