Knauer, Shirley K. and Kraemer, Oliver H. and Knoesel, Thomas and Engels, Knut and Roedel, Franz and Kovacs, Adorjan F. and Dietmaier, Wolfgang and Klein-Hitpass, Ludger and Habtemichael, Negusse and Schweitzer, Andrea and Brieger, Juergen and Roedel, Claus and Mann, Wolf and Petersen, Iver and Heinzel, Thorsten and Stauber, Roland H. (2007) Nuclear export is essential for the tumor-promoting activity of survivin. FASEB JOURNAL, 21 (1). pp. 207-216. ISSN 0892-6638,
Full text not available from this repository. (Request a copy)Abstract
Survivin appears to function as an apoptosis inhibitor and a regulator of cell division during development and tumorigenesis. Here we report the molecular characterization of the nucleocytoplasmic transport of survivin and its potential implications for tumorigenesis. We identified an evolutionary conserved Crm1-dependent nuclear export signal (NES) in survivin. In dividing cells, the NES is essential for tethering survivin and the survivin/Aurora-B kinase complex to the mitotic machinery, which in turn appears to be essential for proper cell division. In addition, export seems to be required for the cytoprotective activity of survivin, as export-deficient survivin fails to protect tumor cells against chemo- and radiotherapy-induced apoptosis. These findings appear to be clinically relevant since preferential nuclear localization of survivin correlated with enhanced survival in colorectal cancer patients. Targeting survivin's nuclear export by the application of NES-specific antibodies promoted its nuclear accumulation and inhibited its cytoprotective function. We demonstrate that nuclear export is essential for the biological activity of survivin and promote the identification of molecular decoys to specifically interfere with survivin's nuclear export as potential anticancer therapeutics.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NUCLEOCYTOPLASMIC TRANSPORT; CYTOPLASMIC EXPRESSION; THERAPEUTIC TARGET; IN-VIVO; CANCER; APOPTOSIS; CELLS; LOCALIZATION; PROTEINS; PHOSPHORYLATION; nucleocytoplasmic transport; apoptosis; Crm1; head and neck cancer; colorectal cancer; cancer therapy; LMB; cisplatin; valproic acid; HDAC |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Jan 2021 07:45 |
| Last Modified: | 12 Jan 2021 07:45 |
| URI: | https://pred.uni-regensburg.de/id/eprint/33416 |
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