title: An Old Flame Never Dies: Survivin in Cancer and Cellular Senescence.
abstract: Survivin (BIRC5) is highly expressed in the vast majority of human cancers and is associated with chemotherapy resistance, increased tumor recurrence and shortened patient survival, making it an attractive therapeutic target. Initially identified as an inhibitor of apoptosis protein, it also plays a major role in the regulation of cell division. As such, it acts as a subunit of the chromosomal passenger complex, composed of the mitotic kinase aurora B, borealin and inner centromere protein, and is essential for proper chromosome segregation and cytokinesis. For both biological functions, interaction of survivin's nuclear export signal with the nuclear export receptor chromosome region maintenance 1 is absolutely essential. The timely orchestration of survivin's wide protein interaction repertoire is further modulated by different posttranslational modifications occurring in a cell-cycle-dependent manner. Recent data furthermore indicate additional roles of survivin in the DNA damage response, contributing to therapy resistance, yet the underlying molecular details are still not completely resolved. This also holds true for a potential involvement of survivin in senescence regulation. An age-related accumulation of survivin probably contributes to the apoptosis resistance observed in aged as well as in senescent cells, while it might promote escape from therapy-induced senescence. This review seeks to integrate the current knowledge on survivin's diverse and complex biological functions. By linking the 'old' facts about survivin with recent findings in research areas such as DNA damage response and aging, we want to highlight survivin's crucial role in a variety of cellular processes.
authors.affiliation: Institute for Molecular Biology II, Centre for Medical Biotechnology (ZMB), University of Duisburg-Essen, Essen, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Unruhe
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schröder
authors.forename: Désirée
authors.initials: D
authors.lastname: Wünsch
authors.forename: Shirley K
authors.initials: SK
authors.lastname: Knauer
mesh_terms: D000375:Aging; D017209:Apoptosis; D016922:Cellular Senescence; D004260:DNA Repair; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D008938:Mitosis; D009369:Neoplasms / Q000378:metabolism*; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin