title: Differential subcellular localization of functionally divergent survivin splice variants.
abstract: Survivin is an inhibitor of apoptosis protein (IAP) that is markedly overexpressed in most cancers. We identified two novel functionally divergent splice variants, i.e. non-antiapoptotic survivin-2B and antiapoptotic survivin-deltaEx3. Because survivin-2B might be a naturally occurring antagonist of antiapoptotic survivin variants, we analyzed the subcellular distribution of these proteins. PSORT II analysis predicted a preferential cytoplasmic localization of survivin and survivin-2B, but a preferential nuclear localization of survivin-deltaEx3. GFP-tagged survivin variants confirmed the predicted subcellular localization and additionally revealed a cell cycle-dependent nuclear accumulation of survivin-deltaEx3. Moreover, a bipartite nuclear localization signal found exclusively in survivin-deltaEx3 may support cytoplasmic clearance of survivin-deltaEx3. In contrast to the known association between survivin and microtubules or centromeres during mitosis, no corresponding co-localization became evident for survivin-deltaEx3 or survivin-2B. In conclusion, our study provided data on a differential subcellular localization of functionally divergent survivin variants, suggesting that survivin isoforms may perform different functions in distinct subcellular compartments and distinct phases of the cell cycle.
authors.affiliation: Institute of Pathology, Heinrich Heine-University, Duesseldorf, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Mahotka
authors.forename: J
authors.initials: J
authors.lastname: Liebmann
authors.forename: M
authors.initials: M
authors.lastname: Wenzel
authors.forename: C V
authors.initials: CV
authors.lastname: Suschek
authors.forename: M
authors.initials: M
authors.lastname: Schmitt
authors.forename: H E
authors.initials: HE
authors.lastname: Gabbert
authors.forename: C D
authors.initials: CD
authors.lastname: Gerharz
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics; D002451:Cell Compartmentation / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D008164:Luminescent Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D000077022:Survivin; D049452:Green Fluorescent Proteins