Clinico-pathologic relevance of Survivin splice variant expression in cancer

Abstract

Survivin is a member of the inhibitor of apoptosis (IAP) family and has multifunctional properties that include aspects of proliferation, invasion and cell survival control. Survivin is a promising candidate for targeted cancer therapy as its expression is associated with poor clinical outcome, more aggressive clinico-pathologic features, and resistance to radiation and chemotherapy. In the present review the different properties of the Survivin splice variants are discussed and their activities correlated with different aspects of cancer cell biology, to include subcellular location. Special emphasis is placed on our current understanding of these Survivin splice variants influence on each other and on the phenotypic responses to therapy that they may control.

Keywords: Cancer; Splice variants; Survivin.

Figure 1

Multiple alignment of Survivin splice variants. Many residues and regions important to the anti-apoptotic functions of WT Survivin are highlighted and shared with other splice variants (*indicates the residue is common to all isoforms). This includes much of the BIR domain highlighted in the WT sequence (F13–V89), the XIAP binding region (K15–M38), and S20 which can disrupt Survivin and XIAP binding when phosphorylated[20]. Other functionally important residues include T34 which can also be phosphorylated[22], T48[23], Smac/Diablo binding residues L64[24] and D71[25], as well as the K79–G83 Hsp90 binding region[27], and V89–L98 Crm-1 dependent Nuclear Export Signal (NES) sequence[29].