The Survivin-Crm1 interaction is essential for chromosomal passenger complex localization and function.
The chromosomal passenger complex (CPC) of Aurora-B, Borealin, INCENP (inner centromere protein) and Survivin coordinates essential chromosomal and cytoskeletal events during mitosis. Here, we show that the nuclear export receptor Crm1 is crucially involved in tethering the CPC to the centromere by interacting with a leucine-rich nuclear export signal (NES), evolutionarily conserved in all mammalian Survivin proteins. We show that inhibition of the Survivin-Crm1 interaction by treatment with leptomycin B or by RNA-interference-mediated Crm1 depletion prevents centromeric targeting of Survivin. The genetic inactivation of the Survivin-Crm1 interaction by mutation of the NES affects the correct localization and function of Survivin and the CPC during mitosis. By contrast, CPC assembly does not seem to require the Survivin-Crm1 interaction. Our report shows the functional significance of the Survivin-Crm1 interface and provides a novel link between the mitotic effector Crm1 and the CPC.
Knauer
Shirley K
SK
Georg-Speyer-Haus, Paul-Ehrlich-Strasse 42-44, Frankfurt D-60596, Germany.
Bier
Carolin
C
Habtemichael
Negusse
N
Stauber
Roland H
RH
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002503:Centromere / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D049790:Nuclear Export Signals; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D000077022:Survivin; D014162:Transfection; D000097606:Exportin 1 Protein
D002868:Chromosomal Proteins, Non-Histone; D005231:Fatty Acids, Unsaturated; D051034:Inhibitor of Apoptosis Proteins; D028884:Karyopherins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D049790:Nuclear Export Signals; D018160:Receptors, Cytoplasmic and Nuclear; D000077022:Survivin; D000097606:Exportin 1 Protein; C107489:BIRC5 protein, human; C038753:leptomycin B