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Title
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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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Author
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Abstract
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| 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, TDVD(133) 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 |
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Language
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English
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Source (journal)
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Cell Death and Disease. - -
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Publication
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2010
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ISSN
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2041-4889
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DOI
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10.1038/CDDIS.2009.16
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Volume/pages
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1
(2010)
, p. 1-10
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Article Reference
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e18
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ISI
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000279616300017
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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