Differential subcellular localization of functionally divergent survivin splice variants.
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.
Mahotka
C
C
Institute of Pathology, Heinrich Heine-University, Duesseldorf, Germany.
Liebmann
J
J
Wenzel
M
M
Suschek
C V
CV
Schmitt
M
M
Gabbert
H E
HE
Gerharz
C D
CD
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
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