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Isoform-specific silencing of the Livin gene by RNA interference defines Livin β as key mediator of apoptosis inhibition in HeLa cells

Isoform-specific silencing of the Livin gene by RNA interference defines Livin β as key mediator... Livin (alternatively called ML-IAP or KIAP) is a cancer-associated member of the antiapoptotic inhibitor of apoptosis protein family. Two splicing variants of Livin, designated Livin α and Livin β, have been identified. The significance of these isoforms for Livin-mediated apoptosis inhibition is largely unclear. Using an isoform-specific RNA interference (RNAi) strategy, we silenced endogenous Livin expression in HeLa cells. We found that the targeted inhibition of Livin β, but not of Livin α, blocked the growth of HeLa cells in clonogenic survival assays. In addition, silencing of Livin β, but not of Livin α, sensitized HeLa cells to different proapoptotic stimuli such as UV irradiation, tumor necrosis factor α, or etoposide. These events were linked to activation of caspase-3 and increased poly(ADP-ribose) polymerase cleavage, specifically upon silencing of Livin β. The proapoptotic sensitization of HeLa cells upon RNAi-mediated silencing of the endogenous livin gene was specifically reverted by ectopic expression of Livin β but not of Livin α. We conclude that the Livin β isoform plays the key role for the antiapoptotic protection of HeLa cells by the livin gene. Our results show that the Livin isoforms can strongly differ in their functional significance for the antiapoptotic resistance of tumor cells. Studies evaluating Livin as a novel diagnostic and prognostic tumor marker should benefit from isoform-specific expression analyses. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Molecular Medicine Springer Journals

Isoform-specific silencing of the Livin gene by RNA interference defines Livin β as key mediator of apoptosis inhibition in HeLa cells

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References (36)

Publisher
Springer Journals
Copyright
Copyright © 2005 by Springer-Verlag
Subject
Biomedicine; Internal Medicine ; Molecular Medicine
ISSN
0946-2716
eISSN
1432-1440
DOI
10.1007/s00109-005-0021-5
pmid
16437214
Publisher site
See Article on Publisher Site

Abstract

Livin (alternatively called ML-IAP or KIAP) is a cancer-associated member of the antiapoptotic inhibitor of apoptosis protein family. Two splicing variants of Livin, designated Livin α and Livin β, have been identified. The significance of these isoforms for Livin-mediated apoptosis inhibition is largely unclear. Using an isoform-specific RNA interference (RNAi) strategy, we silenced endogenous Livin expression in HeLa cells. We found that the targeted inhibition of Livin β, but not of Livin α, blocked the growth of HeLa cells in clonogenic survival assays. In addition, silencing of Livin β, but not of Livin α, sensitized HeLa cells to different proapoptotic stimuli such as UV irradiation, tumor necrosis factor α, or etoposide. These events were linked to activation of caspase-3 and increased poly(ADP-ribose) polymerase cleavage, specifically upon silencing of Livin β. The proapoptotic sensitization of HeLa cells upon RNAi-mediated silencing of the endogenous livin gene was specifically reverted by ectopic expression of Livin β but not of Livin α. We conclude that the Livin β isoform plays the key role for the antiapoptotic protection of HeLa cells by the livin gene. Our results show that the Livin isoforms can strongly differ in their functional significance for the antiapoptotic resistance of tumor cells. Studies evaluating Livin as a novel diagnostic and prognostic tumor marker should benefit from isoform-specific expression analyses.

Journal

Journal of Molecular Medicine – Springer Journals

Published: Dec 31, 2005

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