title: 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 NH2 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 survivin1-120 and survivin11-142 were able to protect cells against TRAIL-mediated apoptosis, but when challenged with irradiation cells expressing survivin11-142 had no survival advantage. During mitosis, however, removing the NH2 terminal 10 amino acids (survivin11-142) had no apparent effect but truncating 22 amino acids from the C-terminus (survivin1-120) 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 NH2 terminus is dispensable for apoptosis and mitosis but required for protection from irradiation.
authors.affiliation: a From the School of Life Sciences ; University of Nottingham; Queen's Medical Centre ; Nottingham , UK.
authors.forename: Sally P
authors.initials: SP
authors.lastname: Wheatley
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011839:Radiation, Ionizing; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D000077022:Survivin; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
chemical_list: C107489:BIRC5 protein, human; C490157:CDCA8 protein, human; D018797:Cell Cycle Proteins; D051034:Inhibitor of Apoptosis Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D000077022:Survivin; D053221:TNF-Related Apoptosis-Inducing Ligand; D020169:Caspases
keywords: CPC, chromosomal passenger complex; CPP, chromosomal passenger protein; IAP, inhibitor of apoptosis; IR, irradiation; NES, nuclear exportation signal; SVN, survivin; TRAIL, Tumor-necrosis factor Responsive Apoptosis Inducing Ligand; WT, wild type; apoptosis; cancer; irradiation; mitosis; survivin