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Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria

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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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Chicago
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.
APA
Wirawan, E., Vande Walle, L., Kersse, K., Cornelis, S., Claerhout, S., Vanoverberghe, I., Roelandt, R., 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.
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.
MLA
Wirawan, Ellen, Lieselotte Vande Walle, Kristof Kersse, 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 1 (2010): n. pag. Print.
@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},
  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://dx.doi.org/10.1038/cddis.2009.16},
  volume       = {1},
  year         = {2010},
}

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