Knauer, Shirley K. and Bier, Carolin and Schlag, Peter and Fritzmann, Johannes and Dietmaier, Wolfgang and Roedel, Franz and Klein-Hitpass, Ludger and Kovacs, Adorian F. and Doering, Claudia and Hansmann, Martin-Leo and Hofmann, Wolf-Karsten and Kunkel, Martin and Brochhausen, Christoph and Engels, Knut and Lippert, Burkhard M. and Mann, Wolf and Stauber, Roland H. (2007) The survivin isoform Survivin-3B is cytoprotective and can function as a chromosomal passenger complex protein. CELL CYCLE, 6 (12). pp. 1502-1509. ISSN 1538-4101,
Full text not available from this repository. (Request a copy)Abstract
Survivin is described as a bifunctional protein inhibiting apoptosis and regulating mitosis. However, the biological functions and contributions to cancer progression of survivin splice variants are controversially discussed. We here show that the intracellular localization of these splice variants depends on a Crm1-dependent nuclear export signal (NES) present in survivin, survivin(-2B) and survivin(-3B), but absent in survivin(-Delta Ex3) and survivin(-2 alpha). Survivin isoforms lack an active nuclear import signal and are able to enter the nucleus by passive diffusion. Only survivin(-3B) but none of the other splice variants is cytoprotective and able to efficiently interact with chromosomal passenger complex (CPC) proteins. The NES together with efficient CPC formation is required for the cytoprotective activity of survivin isoforms, as well as for their correct localization and function during cell division. In the tumours from breast, colorectal, head and neck cancer, lymphoma and leukemia patients, survivin and survivin(-2B) were found overexpressed. However, survivin was the predominant form detected, and the other survivin isoforms were only expressed at low levels in tumours. Our data provide a molecular rationale for the localization and activity of survivin variants, and conclude that survivin isoforms are unlikely to modulate survivin in trans in cancer patients.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | IN-VIVO EXPRESSION; SPLICE VARIANTS; NUCLEOCYTOPLASMIC TRANSPORT; SUBCELLULAR-LOCALIZATION; MOLECULAR-MECHANISM; NUCLEAR EXPORT; BREAST-CANCER; CELL-DEATH; SURVIVIN-DELTAEX3; ANGIOGENESIS; nucleocytoplasmic transport; Crm1; apoptosis; LMB; cell cycle; chromosomal passenger; protein; dimerization; protein interaction; trans-dominance |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Dec 2020 13:34 |
| Last Modified: | 07 Dec 2020 13:34 |
| URI: | https://pred.uni-regensburg.de/id/eprint/32610 |
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