Human survivin is a kinetochore-associated passenger protein

Survivin, a dimeric baculovirus inhibitor of apoptosis repeat (BIR) motif p rotein that is principally expressed in G2 and mitosis, has been associated with protection against apoptosis of cells that exit mitosis aberrantly. M ammalian survivin has been reported to associate with centrosomes and with the mitotic spindle. We have expressed a human hemagglutinin-tagged survivi n plasmid to determine its localization, and find instead that it clearly a cts as a passenger protein. In HeLa cells, survivin first associates with t he kinetochores, and then translocates to the spindle midzone during anapha se and, finally, to the midbody during cell cleavage. Its localization is s imilar to that of TD-60, a known passenger protein. Both a point mutation i n the baculovirus IAP repeat motif (C84A) and a COOH-terminal deletion muta nt (Delta 106) of survivin fail to localize to either kinetochores or midbo dies, but neither interferes with cell cleavage. The interphase localizatio n of survivin is cell cycle regulated since in permanently transfected NIH3 T3 cells it is excluded from the nuclei until G2, where it localizes with c entromeres. Survivin remains associated with mitotic kinetochores when micr otubule assembly is disrupted and its localization is thus independent of m icrotubules. We conclude that human survivin is positioned to have an impor tant function in the mechanism of cell cleavage.