**5. Isoforms**

In addition to "wild type" survivin, alias survivin-alpha/BIRC5, several splice variants exist. The two most extensively studied are alternatively spliced at the exon 2-intron border, which generates the variants, survivin 2B, with an additional 23 aa after exon 2, and delta exon 3 (DeX3) which incurs a frame shift that results in a completely distinct C-terminal sequence (Mahotka et al., 2002; Mahotka et al., 1999). We, and others, have shown that consistent with the central positioning of the NES, 2B retains this sequence and is predominantly cytoplasmic when ectopically expressed in cultured cells, while DeX3 is nuclear, not only because it lacks the two NES sequences, but because it has its own, functional NLS in its C-terminus (Mahotka et al., 2002; Noton et al., 2006; Rodriguez et al., 2002). As for the nuclear-cytoplasmic debate, the prognostic importance of the expression of these forms is also a matter of controversy, and there are many reports correlating the expression of transcripts of these variants and localisation of their gene products with disease severity, most recently (Antonacopoulou et al., 2011) and (Takeno et al., 2010).
