Differential subcellular localization of functionally divergent survivin splice variants
Differential subcellular localization of functionally divergent survivin splice variants
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DOI：
10.1038/sj.cdd.4401091
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发表时间：
2002-12-01
影响因子：
12.4
通讯作者：
Gerharz, CD
中科院分区：
文献类型：
--
作者：
Mahotka, C;Liebmann, J;Gerharz, CD
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-anti-apoptotic 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 11 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.
