Differential subcellular localization of functionally divergent survivin splice variants

Cell Death Differ. 2002 Dec;9(12):1334-42. doi: 10.1038/sj.cdd.4401091.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics*
  • Apoptosis / genetics
  • Cell Compartmentation / genetics
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cytoplasm / genetics
  • Cytoplasm / metabolism
  • Eukaryotic Cells / cytology
  • Eukaryotic Cells / metabolism*
  • Green Fluorescent Proteins
  • HeLa Cells
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism
  • Luminescent Proteins
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Molecular Sequence Data
  • Neoplasm Proteins
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Recombinant Fusion Proteins
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Survivin


  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Ki-67 Antigen
  • Luminescent Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Protein Isoforms
  • Recombinant Fusion Proteins
  • Survivin
  • Green Fluorescent Proteins