title: Human survivin is a kinetochore-associated passenger protein.
abstract: 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 (Delta106) 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.
authors.affiliation: Institut de Biologie Structurale Jean-Pierre Ebel (Commissariat á l'Energie Atomique-Centre National de la Recherche Scientifique), 38027 Grenoble Cedex 1, France.
authors.forename: D A
authors.initials: DA
authors.lastname: Skoufias
authors.forename: C
authors.initials: C
authors.lastname: Mollinari
authors.forename: F B
authors.initials: FB
authors.lastname: Lacroix
authors.forename: R L
authors.initials: RL
authors.lastname: Margolis
mesh_terms: D016475:3T3 Cells; D020816:Amino Acid Motifs; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002455:Cell Division; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D018386:Kinetochores / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins; D011485:Protein Binding; D021381:Protein Transport; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism; D000077022:Survivin; D016335:Zinc Fingers
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D000077022:Survivin