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- Title
Differential subcellular localization of functionally divergent survivin splice variants.
- Authors
Mahotka, C.; Liebmann, J.; Wenzel, M.; Suschek, C.V.; Schmitt, M.; Gabbert, H.E.; Gerharz, C.D.
- Abstract
Survivin is an inhibitor of apoptosis protein (lAP) 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-28 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 subceilular compartments and distinct phases of the cell cycle.
- Subjects
APOPTOSIS; CANCER
- Publication
Cell Death & Differentiation, 2002, Vol 9, Issue 12, p1334
- ISSN
1350-9047
- Publication type
Article
- DOI
10.1038/sj.cdd.4401091