Nuclear Survivin: Cellular Consequences and Therapeutic Implications

Abstract

Survivin is a cancer associated protein that is present in all embryonic cells, but whose expression is normally limited to actively proliferating cells in adults. During mitosis it is part of a conserved complex of chromosomal passenger proteins (CPPs), which is essential for chromosome biorientation and cell division (Ruchaud et al., 2007). Defects in CPP function cause errors in mitosis and cytokinesis and can lead to genomic instability, or “aneuploidy”, a status indicative of tumorigenesis. First discovered by Altieri and coworkers (Ambrosini et al., 1998), survivin is the fourth most upregulated mRNA in the cancer transcriptome (Velculescu et al., 1999), and in many tumours its expression is detected throughout the cell cycle. Importantly increased survivin abundance correlates with tumour resistance to conventional radiation and chemotherapies, a correlation recapitulated in cultured cells in the laboratory (Chakravarti et al., 2004; Colnaghi et al., 2006). While involvement in mitosis alone is a valid reason for considering a protein as a biomarker, or a target for cancer therapy, the oncotherapeutic potential of survivin is compounded by the fact that it is also an inhibitor of cell death (for review see Altieri, 2008). The principle aim of this article is to highlight the manifestations of survivin expression in the nucleus and to discuss how these might be exploited for oncotherapeutic gain.