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-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.
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Abbreviations
- IAP:
-
inhibitor of apoptosis
- BIR:
-
baculovirus inhibitory repeat
- GFP:
-
green fluorescent protein
- PSORT:
-
program for detecting the protein sorting signals and predicting their subcellular localization
- NLS:
-
nuclear localization signal
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Acknowledgements
We thank Sigrid Khalil, Michael Ringler, and Martina Bellack for technical assistance. The results of this work are part of the Ph.D. thesis of J Liebmann and M Wenzel. This work was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG).
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Edited by D Altieri
During the reviewing process of our manuscript, Rodriguez et al. (Exp. Cell. Res., 275:44, 2002) described corresponding observations on the subcellular localization of survivin-ΔEx3.
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Mahotka, C., Liebmann, J., Wenzel, M. et al. Differential subcellular localization of functionally divergent survivin splice variants. Cell Death Differ 9, 1334–1342 (2002). https://doi.org/10.1038/sj.cdd.4401091
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DOI: https://doi.org/10.1038/sj.cdd.4401091
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