Title: Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria
Authors: Wirawan, E
Vande Walle, L
Kersse, K
Cornelis, S
Claerhout, Sofie
Vanoverberghe, I
Roelandt, R
De Rycke, R
Verspurten, J
Declercq, W
Agostinis, Patrizia
Vanden Berghe, T
Lippens, S
Vandenabeele, P # ×
Issue Date: Jan-2010
Publisher: Nature Publishing Group
Series Title: Cell Death & Disease vol:1 pages:e18
Article number: 10.1038/cddis.2009.16
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 DQLD(149), cleavage at which yields fragments lacking the autophagy-inducing 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. Cell Death and Disease (2010) 1, e18; doi:10.1038/cddis.2009.16; published online 21 January 2010
ISSN: 2041-4889
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Cell Death Research & Therapy
× corresponding author
# (joint) last author

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