Survivin's dual role: an export's view.
Survivin is proposed to function as a mitotic regulator and an apoptosis inhibitor during development and pathogenesis. As such, survivin has aroused keen interest in disparate areas of basic and translational research. Survivin acts as a subunit of the chromosomal passenger complex (CPC), composed of the mitotic kinase Aurora-B, Borealin and INCENP, and is essential for proper chromosome segregation and cytokinesis. Our recent findings indicate that the nuclear export receptor Crm1 is critically involved in tethering the CPC to the centromere by interacting with a leucine-rich nuclear export signal (NES), evolutionary conserved in all mammalian survivin proteins. In addition, the survivin/Crm1 interaction seems to be required for the cytoprotective activity of survivin, because export deficient survivin fails to protect tumor cells against cancer therapy-induced apoptosis. These findings appear to be of clinical relevance since preferential nuclear localization of survivin turned out to be a favorable prognostic factor in cancer patients. Besides emphasizing the functional significance of the Crm1/survivin interface, we suggest to exploit the pharmacogenetic interference with survivin's export as a novel strategy to antagonize survivin's activity.
Knauer
Shirley K
SK
Department of Otorhinolaryngology, Molecular and Cellular Oncology, University of Mainz, Mainz, Germany.
Mann
Wolf
W
Stauber
Roland H
RH
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000077022:Survivin
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin