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 baculovirus es. Although baculoviral IAP proteins regulate cell death, the yeast Surviv in homolog Bir1 is involved in cell division. To determine the function of Survivin in mammals, we analyzed the pattern of localization of Survivin pr otein during the cell cycle, and deleted its gene by homologous recombinati on 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 m idzone during anaphase/telophase, and disappeared at the end of telophase. In the mouse, Survivin was required for mitosis during development. Null em bryos showed disrupted microtubule formation, became polyploid, and failed to survive beyond 4.5 days post coitum. This phenotype, and the cell-cycle localization of Survivin, resembled closely those of INCENP. Because the ye ast homolog of INCENP, Sli15, regulates the Aurora kinase homolog Ip\1p, an d the yeast Survivin homolog Bir1 binds to Ndc10p, a substrate of Ip\1 p, y east Survivin, INCENP and Aurora homologs function in concert during cell d ivision. Conclusions: In vertebrates, Survivin and INCENP have related roles in mito sis, coordinating events such as microtubule organization, cleavage-furrow formation and cytokinesis. Like their yeast homologs Bir1 and Sli15, they m ay also act together with the Aurora kinase.