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tLivin Displays Flexibility by Promoting Alternative Cell Death Mechanisms
Livin is a member of the Inhibitor of Apoptosis (IAP) protein family that inhibits apoptosis triggered by a variety of stimuli. We previously demonstrated that while Livin inhibits caspase activity, caspases can cleave Livin to produce a truncated protein, tLivin and that this newly formed tLivin pa...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4069184/ https://www.ncbi.nlm.nih.gov/pubmed/24960127 http://dx.doi.org/10.1371/journal.pone.0101075 |
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author | Shiloach, Tamar Berens, Christian Danke, Christina Waiskopf, Ortal Perlman, Riki Ben-Yehuda, Dina |
author_facet | Shiloach, Tamar Berens, Christian Danke, Christina Waiskopf, Ortal Perlman, Riki Ben-Yehuda, Dina |
author_sort | Shiloach, Tamar |
collection | PubMed |
description | Livin is a member of the Inhibitor of Apoptosis (IAP) protein family that inhibits apoptosis triggered by a variety of stimuli. We previously demonstrated that while Livin inhibits caspase activity, caspases can cleave Livin to produce a truncated protein, tLivin and that this newly formed tLivin paradoxically induces cell death. However to date, the mechanism of tLivin-induced cell death is not fully understood. In this study, we set out to characterize the form of cell death mediated by tLivin. Here we demonstrate that, unlike most death-promoting proteins, tLivin is a flexible inducer of cell death capable of promoting necrosis or apoptosis in different cell lines. The unusual flexibility of tLivin is displayed by its ability to activate an alternative form of cell death when apoptosis is inhibited. Thus, tLivin can promote more than one form of cell death in the same cell type. Interestingly, in cells where tLivin induces necrosis, deletion of the caspase binding BIR domain results in tLivin-induced apoptosis, suggesting the BIR domain can potentially hamper the ability of tLivin to induce apoptosis. We further elucidate that tLivin activates the JNK pathway and both tLivin-induced apoptosis and necrosis are partially mediated by JNK activity. Acquired resistance to apoptosis, common in many tumors, impinges on the efficiency of conventional anti-cancer agents that function primarily by inducing apoptosis. The ability of tLivin to induce death of apoptosis-compromised cells makes it an attractive candidate for targeted cancer therapy. |
format | Online Article Text |
id | pubmed-4069184 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40691842014-06-27 tLivin Displays Flexibility by Promoting Alternative Cell Death Mechanisms Shiloach, Tamar Berens, Christian Danke, Christina Waiskopf, Ortal Perlman, Riki Ben-Yehuda, Dina PLoS One Research Article Livin is a member of the Inhibitor of Apoptosis (IAP) protein family that inhibits apoptosis triggered by a variety of stimuli. We previously demonstrated that while Livin inhibits caspase activity, caspases can cleave Livin to produce a truncated protein, tLivin and that this newly formed tLivin paradoxically induces cell death. However to date, the mechanism of tLivin-induced cell death is not fully understood. In this study, we set out to characterize the form of cell death mediated by tLivin. Here we demonstrate that, unlike most death-promoting proteins, tLivin is a flexible inducer of cell death capable of promoting necrosis or apoptosis in different cell lines. The unusual flexibility of tLivin is displayed by its ability to activate an alternative form of cell death when apoptosis is inhibited. Thus, tLivin can promote more than one form of cell death in the same cell type. Interestingly, in cells where tLivin induces necrosis, deletion of the caspase binding BIR domain results in tLivin-induced apoptosis, suggesting the BIR domain can potentially hamper the ability of tLivin to induce apoptosis. We further elucidate that tLivin activates the JNK pathway and both tLivin-induced apoptosis and necrosis are partially mediated by JNK activity. Acquired resistance to apoptosis, common in many tumors, impinges on the efficiency of conventional anti-cancer agents that function primarily by inducing apoptosis. The ability of tLivin to induce death of apoptosis-compromised cells makes it an attractive candidate for targeted cancer therapy. Public Library of Science 2014-06-24 /pmc/articles/PMC4069184/ /pubmed/24960127 http://dx.doi.org/10.1371/journal.pone.0101075 Text en © 2014 Shiloach et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Shiloach, Tamar Berens, Christian Danke, Christina Waiskopf, Ortal Perlman, Riki Ben-Yehuda, Dina tLivin Displays Flexibility by Promoting Alternative Cell Death Mechanisms |
title | tLivin Displays Flexibility by Promoting Alternative Cell Death Mechanisms |
title_full | tLivin Displays Flexibility by Promoting Alternative Cell Death Mechanisms |
title_fullStr | tLivin Displays Flexibility by Promoting Alternative Cell Death Mechanisms |
title_full_unstemmed | tLivin Displays Flexibility by Promoting Alternative Cell Death Mechanisms |
title_short | tLivin Displays Flexibility by Promoting Alternative Cell Death Mechanisms |
title_sort | tlivin displays flexibility by promoting alternative cell death mechanisms |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4069184/ https://www.ncbi.nlm.nih.gov/pubmed/24960127 http://dx.doi.org/10.1371/journal.pone.0101075 |
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