The Functional Repertoire of Survivin's Tails

Abstract

Survivin is a multitasking protein that can inhibit cell death and that is essential for mitosis. Due to these prosurvival activities and the correlation of its expression with tumor resistance to conventional cancer treatments, survivin has received much attention as a potential oncotherapeutic target. Nevertheless, many questions regarding its exact role at the molecular level remain to be elucidated. In this study we ask whether the extreme C- and NH ₂ termini of survivin are required for it to carry out its cytoprotective and mitotic duties. When assayed for their ability to act as a cytoprotectant, both survivin _1–120 and survivin _11–142 were able to protect cells against TRAIL-mediated apoptosis, but when challenged with irradiation cells expressing survivin _11–142 had no survival advantage. During mitosis, however, removing the NH ₂ terminal 10 amino acids (survivin _11–142) had no apparent effect but truncating 22 amino acids from the C-terminus (survivin _1–120) prevented survivin from transferring to the midzone microtubules during anaphase. Collectively the data herein presented suggest that the C-terminus is required for cell division, and that the NH ₂ terminus is dispensable for apoptosis and mitosis but required for protection from irradiation.