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Published online 25 December 2000. doi:10.1083/jcb.151.7.1575
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© The Rockefeller University Press, 0021-9525/2000//1575 $5.00
The Journal of Cell Biology, Volume 151, Number 7, , 2000 1575-1582

Report

Human Survivin Is a Kinetochore-Associated Passenger Protein



Dimitrios A. Skoufiasa, Cristiana Mollinaria, Françoise B. Lacroixa, and Robert L. Margolisa

a Institut de Biologie Structurale Jean-Pierre Ebel (Commissariat á l'Energie Atomique–Centre National de la Recherche Scientifique), 38027 Grenoble Cedex 1, France
Institut de Biologie Structurale Jean-Pierre Ebel (CEA-CNRS), 41 rue Jules Horowitz, 38027 Grenoble cedex 1, France.(33) 4 76 88 54 94(33) 4 76 88 96 16

margolis{at}ibs.fr

Survivin, a dimeric baculovirus inhibitor of apoptosis repeat (BIR) motif protein that is principally expressed in G2 and mitosis, has been associated with protection against apoptosis of cells that exit mitosis aberrantly. Mammalian survivin has been reported to associate with centrosomes and with the mitotic spindle. We have expressed a human hemagglutinin-tagged survivin plasmid to determine its localization, and find instead that it clearly acts as a passenger protein. In HeLa cells, survivin first associates with the kinetochores, and then translocates to the spindle midzone during anaphase and, finally, to the midbody during cell cleavage. Its localization is similar to that of TD-60, a known passenger protein. Both a point mutation in the baculovirus IAP repeat motif (C84A) and a COOH-terminal deletion mutant ({Delta}106) of survivin fail to localize to either kinetochores or midbodies, but neither interferes with cell cleavage. The interphase localization of survivin is cell cycle regulated since in permanently transfected NIH3T3 cells it is excluded from the nuclei until G2, where it localizes with centromeres. Survivin remains associated with mitotic kinetochores when microtubule assembly is disrupted and its localization is thus independent of microtubules. We conclude that human survivin is positioned to have an important function in the mechanism of cell cleavage.

Key Words: survivin • mitosis • kinetochore • passenger protein • cytokinesis

© 2000 The Rockefeller University Press

Abbreviations used in this paper: BIR, baculovirus IAP repeat; HA, hemagglutinin; IAP, inhibitor of apoptosis protein.


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