Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype.
BACKGROUND
Survivin is a mammalian protein that carries a motif typical of the inhibitor of apoptosis (IAP)proteins, first identified in baculoviruses. Although baculoviral IAP proteins regulate cell death, the yeast Survivin homolog Bir1 is involved in cell division. To determine the function of Survivin in mammals, we analyzed the pattern of localization of Survivin protein during the cell cycle, and deleted its gene by homologous recombination in mice.


RESULTS
In human cells, Survivin appeared first on centromeres bound to a novel para-polar axis during prophase/metaphase, relocated to the spindle midzone during anaphase/telophase, and disappeared at the end of telophase. In the mouse, Survivin was required for mitosis during development. Null embryos showed disrupted microtubule formation, became polyploid, and failed to survive beyond 4.5days post coitum. This phenotype, and the cell-cycle localization of Survivin, resembled closely those of INCENP. Because the yeast homolog of INCENP, Sli15, regulates the Aurora kinase homolog Ipl1p, and the yeast Survivin homolog Bir1 binds to Ndc10p, a substrate of Ipl1p, yeast Survivin, INCENP and Aurora homologs function in concert during cell division.


CONCLUSIONS
In vertebrates, Survivin and INCENP have related roles in mitosis, coordinating events such as microtubule organization, cleavage-furrow formation and cytokinesis. Like their yeast homologs Bir1 and Sli15, they may also act together with the Aurora kinase.
Uren
A G
AG
The Walter and Eliza Hall Institute of Medical Research, Post Office Royal Melbourne Hospital, 3050,., Victoria, Australia.
Wong
L
L
Pakusch
M
M
Fowler
K J
KJ
Burrows
F J
FJ
Vaux
D L
DL
Choo
K H
KH
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism; D002503:Centromere / Q000378:metabolism; D051936:Centromere Protein B; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism*; D002875:Chromosomes / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D005456:Fluorescent Dyes; D017353:Gene Deletion; D005838:Genotype; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D051379:Mice; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008938:Mitosis; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment; D000077022:Survivin; D014404:Tubulin / Q000378:metabolism
D001324:Autoantigens; C107489:BIRC5 protein, human; C497926:CENPB protein, human; C497927:Cenpb protein, mouse; D051936:Centromere Protein B; D002868:Chromosomal Proteins, Non-Histone; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D005456:Fluorescent Dyes; C083767:INCENP protein, human; C513185:Incenp protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D000077022:Survivin; D014404:Tubulin