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TY - JOUR AU - Mahotka, C. AU - Liebmann, J. AU - Wenzel, M. AU - Suschek, C V AU - Schmitt, M. AU - Gabbert, H E AU - Gerharz, C D PY - 2002 DA - 2002/12/01 TI - Differential subcellular localization of functionally divergent survivin splice variants JO - Cell Death & Differentiation SP - 1334 EP - 1342 VL - 9 IS - 12 AB - 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-ΔEx3. 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-ΔEx3. GFP-tagged survivin variants confirmed the predicted subcellular localization and additionally revealed a cell cycle-dependent nuclear accumulation of survivin-ΔEx3. Moreover, a bipartite nuclear localization signal found exclusively in survivin-ΔEx3 may support cytoplasmic clearance of survivin-ΔEx3. In contrast to the known association between survivin and microtubules or centromeres during mitosis, no corresponding co-localization became evident for survivin-ΔEx3 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. SN - 1476-5403 UR - https://doi.org/10.1038/sj.cdd.4401091 DO - 10.1038/sj.cdd.4401091 ID - Mahotka2002 ER -