Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria
- Author
- Ellen Wirawan, Lieselotte Vande Walle (UGent) , Kristof Kersse (UGent) , Sigrid Cornelis, S Claerhout, Isabel Vanoverberghe (UGent) , Ria Roelandt (UGent) , Riet De Rycke (UGent) , Jelle Verspurten (UGent) , Wim Declercq (UGent) , P Agostinis, Tom Vanden Berghe (UGent) , Saskia Lippens (UGent) and Peter Vandenabeele (UGent)
- Organization
- Abstract
- Autophagy and apoptosis are two important and interconnected stress-response mechanisms. However, the molecular interplay between these two pathways is not fully understood. To study the fate and function of autophagic proteins at the onset of apoptosis, we used a cellular model system in which autophagy precedes apoptosis. IL-3 depletion of Ba/F3 cells caused caspase (casp)-mediated cleavage of Beclin-1 and PI3KC3, two crucial components of the autophagy-inducing complex. We identified two casp cleavage sites in Beclin-1, TDVD133 and DQLD149, cleavage at which yields fragments lacking the autophagyinducing capacity. Noteworthy, the C-terminal fragment, Beclin-1-C, localized predominantly at the mitochondria and sensitized the cells to apoptosis. Moreover, on isolated mitochondria, recombinant Beclin-1-C was able to induce the release of proapoptotic factors. These findings point to a mechanism by which casp-dependent generation of Beclin-1-C creates an amplifying loop enhancing apoptosis upon growth factor withdrawal.
- Keywords
- MECHANISMS, INDUCTION, INHIBITION, TUMORIGENESIS
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Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-1021765
- MLA
- Wirawan, Ellen, et al. “Caspase-Mediated Cleavage of Beclin-1 Inactivates Beclin-1-Induced Autophagy and Enhances Apoptosis by Promoting the Release of Proapoptotic Factors from Mitochondria.” CELL DEATH & DISEASE, vol. 1, 2010, doi:10.1038/cddis.2009.16.
- APA
- Wirawan, E., Vande Walle, L., Kersse, K., Cornelis, S., Claerhout, S., Vanoverberghe, I., … Vandenabeele, P. (2010). Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria. CELL DEATH & DISEASE, 1. https://doi.org/10.1038/cddis.2009.16
- Chicago author-date
- Wirawan, Ellen, Lieselotte Vande Walle, Kristof Kersse, Sigrid Cornelis, S Claerhout, Isabel Vanoverberghe, Ria Roelandt, et al. 2010. “Caspase-Mediated Cleavage of Beclin-1 Inactivates Beclin-1-Induced Autophagy and Enhances Apoptosis by Promoting the Release of Proapoptotic Factors from Mitochondria.” CELL DEATH & DISEASE 1. https://doi.org/10.1038/cddis.2009.16.
- Chicago author-date (all authors)
- Wirawan, Ellen, Lieselotte Vande Walle, Kristof Kersse, Sigrid Cornelis, S Claerhout, Isabel Vanoverberghe, Ria Roelandt, Riet De Rycke, Jelle Verspurten, Wim Declercq, P Agostinis, Tom Vanden Berghe, Saskia Lippens, and Peter Vandenabeele. 2010. “Caspase-Mediated Cleavage of Beclin-1 Inactivates Beclin-1-Induced Autophagy and Enhances Apoptosis by Promoting the Release of Proapoptotic Factors from Mitochondria.” CELL DEATH & DISEASE 1. doi:10.1038/cddis.2009.16.
- Vancouver
- 1.Wirawan E, Vande Walle L, Kersse K, Cornelis S, Claerhout S, Vanoverberghe I, et al. Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria. CELL DEATH & DISEASE. 2010;1.
- IEEE
- [1]E. Wirawan et al., “Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria,” CELL DEATH & DISEASE, vol. 1, 2010.
@article{1021765,
abstract = {{Autophagy and apoptosis are two important and interconnected stress-response mechanisms. However, the molecular interplay between these two pathways is not fully understood. To study the fate and function of autophagic proteins at the onset of apoptosis, we used a cellular model system in which autophagy precedes apoptosis. IL-3 depletion of Ba/F3 cells caused caspase (casp)-mediated cleavage of Beclin-1 and PI3KC3, two crucial components of the autophagy-inducing complex. We identified two casp cleavage sites in Beclin-1, TDVD133 and DQLD149, cleavage at which yields fragments lacking the autophagyinducing capacity. Noteworthy, the C-terminal fragment, Beclin-1-C, localized predominantly at the mitochondria and sensitized the cells to apoptosis. Moreover, on isolated mitochondria, recombinant Beclin-1-C was able to induce the release of proapoptotic factors. These findings point to a mechanism by which casp-dependent generation of Beclin-1-C creates an amplifying loop enhancing apoptosis upon growth factor withdrawal.}},
articleno = {{e18}},
author = {{Wirawan, Ellen and Vande Walle, Lieselotte and Kersse, Kristof and Cornelis, Sigrid and Claerhout, S and Vanoverberghe, Isabel and Roelandt, Ria and De Rycke, Riet and Verspurten, Jelle and Declercq, Wim and Agostinis, P and Vanden Berghe, Tom and Lippens, Saskia and Vandenabeele, Peter}},
issn = {{2041-4889}},
journal = {{CELL DEATH & DISEASE}},
keywords = {{MECHANISMS,INDUCTION,INHIBITION,TUMORIGENESIS}},
language = {{eng}},
pages = {{10}},
title = {{Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria}},
url = {{http://doi.org/10.1038/cddis.2009.16}},
volume = {{1}},
year = {{2010}},
}
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