Survivin: Role in Normal Cells and in Pathological Conditions

Survivin, an inhibitor of apoptosis (IAP) containing one baculovirus IAP repeat (BIR) domain, has been reported to be capable of regulating both cellular proliferation and apoptotic cell death. Survivin splice variants, survivin-ΔEx3 and survivin-2B, have apparently retained and lost anti-apoptotic potential, respectively. As survivin was first discovered due to its high homology with effector cell protease receptor (EPR-1), a protein involved in blood coagulation, it has been suggested (but not proven) that EPR-1 may act as a natural anti-sense to survivin in cells. Survivin homologs have been found in non-human species. Survivin expression has been described during embryonic development and in adult cancerous tissues, with greatly reduced expression in adult normal differentiated tissues, particularly if their proliferation index is low. Survivin has been defined as a universal tumor antigen and as the fourth most significant transcriptosome expressed in human tumors. Although survivin is usually located in the cell cytoplasmic region and associated with poor prognosis in cancer, nuclear localisation, indicative of favorable prognosis, has also been reported. Survivin expression has also been reported in a number of proliferating normal adult tissues.Extensive research has been conducted, aimed at increasing our understanding of survivin, by determining its sub-cellular structure and location, mechanism(s) of action and control of expression. While much important information on this molecule has been accumulated, there are still many areas of controversy or limited information. Further research may enable exploitation of survivin overexpression in cancer compared to normal tissues, making survivin a potentially attractive target for cancer therapeutics.