gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

Inhibition of Caspase-3 and –9 by Survivin and its splice variants Survivin-ΔEx3, Survivin-2B and Survivin-3B

Meeting Abstract

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  • corresponding author presenting/speaker Jessica Wagener - Universitätsklinikum, Düsseldorf, Deutschland
  • Helmut E. Gabbert - Universitätsklinikum, Düsseldorf
  • Csaba Mahotka - Universitätsklinikum, Düsseldorf

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO508

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dkk2006/06dkk618.shtml

Veröffentlicht: 20. März 2006

© 2006 Wagener et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: One important hallmark of cancer cells is the resistance to apoptosis. Survivin is a structurally and functional unique member of the inhibitor of apoptosis protein (IAP) family that acts at the interface between apoptosis and cell cycle control. In many human cancers aberrant expression of survivin correlates with poor prognosis and resistance to chemotherapy. Moreover, one of the main impacts of Survivin is the inhibition of caspases. Therefore, we analysed the inhibitory potential of the three Survivin splice variants, i.e. Survivin-DEx3, Survivin-2B, and Survivin-3B in vitro.

Methods: Transfection of HEK293 cells (with GFP-Survivin,GFP-Survivin-ΔEx3, GFP-Survivin-2B and GFP-Survivin-3B), Western Blotting, Caspase-Assays with purified recombinant Survivin, XIAP, and Caspase-3 and –9, and cell extracts of transfected HEK293 cells.

Results: 1. Survivin inhibits recombinant Caspase-3 as well as Caspase-9 in a concentration dependent manner. 2. XIAP enhances the ability of Survivin to inhibit Caspase-3 activity.3. In contrast, Survivin does not increase the potential of XIAP to suppress Caspase-9 activity.4. After transfection with GFP-tagged Survivin, HEK293 cells extracts inhibit recombinant Caspase-9 but not recombinant Caspase-3. 5. HEK293 cell extracts transfected with GFP-Survivin-ΔEx3, GFP-Survivin-2B and GFP-Survivin-3B fail to inhibit both Caspase-3 and -9 activity.

Conclusions: IAPs contribute to the lack of ability of many tumors to undergo apoptosis. Our findings show that – in contrast to Survivin and XIAP – the mainly carboxy-terminal modified splice variants Survivin-ΔEx3, Survivin-2B, and Survivin-3B fail to inhibit caspases-3 and -9 activity in vitro. Therefore, there is a striking evidence for the carboxyterminal region of Survivin to be involved in caspase inhibition.