Subcellular localization and nucleocytoplasmic transport of the chromosomal passenger proteins before nuclear envelope breakdown.
As mitosis progresses, the chromosomal passenger proteins (CPPs) Survivin, Aurora B, INCENP and Borealin dynamically colocalize to mitotic structures. Chromosomal passenger proteins are already expressed during G2, whereas the nuclear envelope is only disassembled at the end of prophase. However, the mechanisms that modulate their nucleocytoplasmic localization before nuclear envelope breakdown (NEB) are poorly characterized. Using epitope-tagged proteins, we show that Aurora B, like Survivin, undergoes CRM1-mediated nucleocytoplasmic shuttling, although both proteins lack identifiable 'classical' nuclear transport signals. On the other hand, INCENP resides more stably in the nucleus and contains multiple nuclear localization signals. Finally, Borealin was detected in the nucleolus and the cytoplasm, but its cytoplasmic localization is not directly regulated by CRM1. Coexpression experiments indicate that the nuclear localization of Aurora B, but not of Survivin, is modulated by INCENP and that Survivin prevents the nucleolar accumulation of Borealin. Our data reveal that, in contrast to their closely related localization during mitosis, the nucleocytoplasmic localization of the CPPs before NEB is largely unrelated. Furthermore, the specific effect of INCENP and Survivin on the localization of Aurora B and Borealin, respectively, suggests that different complexes of CPPs may exist not only during mitosis, as recently reported, but also before NEB.
Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands. ja.rodriguez@vumc.nl
J A
JA
Rodriguez
S M A
SM
Lens
S W
SW
Span
G
G
Vader
R H
RH
Medema
F A E
FA
Kruyt
G
G
Giaccone
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000595:Amino Acid Sequence; D064107:Aurora Kinase B; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D002877:Chromosomes, Human / Q000502:physiology*; D003593:Cytoplasm / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D000077022:Survivin
C107489:BIRC5 protein, human; C490157:CDCA8 protein, human; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C083767:INCENP protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000077022:Survivin; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases