| Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria. | |
| | |
MedLine Citation:
|
PMID: 21364619 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
E Wirawan; L Vande Walle; K Kersse; S Cornelis; S Claerhout; I Vanoverberghe; R Roelandt; R De Rycke; J Verspurten; W Declercq; P Agostinis; T Vanden Berghe; S Lippens; P Vandenabeele |
Related Documents
:
|
21297379 - Bisphosphonate enhances trail sensitivity to human osteosarcoma cells via death recepto... 21321939 - Enterovirus 71 induces integrin β1/egfr-rac1-dependent oxidative stress in sk-n-sh cel... 16377569 - A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake. 21446789 - Effect of chromium and cobalt ions on primary human lymphocytes in vitro. 21156789 - Ursolic acid, a pentacyclin triterpene, potentiates trail-induced apoptosis through p53... 21186369 - Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions o... 10652229 - Involvement of intracellular labile zinc in suppression of devd-caspase activity in hum... 8745239 - Apoptosis in amyotrophic lateral sclerosis is not restricted to motor neurons. bcl-2 ex... 8811009 - A study of the cellular immune response to enteroviruses in humans: identification of c... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Cell death & disease Volume: 1 ISSN: 2041-4889 ISO Abbreviation: Cell Death Dis Publication Date: 2010 |
Date Detail:
|
Created Date: 2011-03-02 Completed Date: 2011-06-23 Revised Date: 2011-07-26 |
Medline Journal Info:
|
Nlm Unique ID: 101524092 Medline TA: Cell Death Dis Country: England |
Other Details:
|
Languages: eng Pagination: e18 Citation Subset: IM |
Affiliation:
|
VIB, Department for Molecular Biomedical Research, Ghent, Belgium. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amino Acid Sequence Animals Apoptosis* Apoptosis Regulatory Proteins / analysis, genetics, metabolism* Autophagy* Caspases / metabolism* Cell Line Humans Interleukin-3 / genetics, metabolism Membrane Proteins / analysis, genetics, metabolism* Mice Mitochondria / metabolism* Phosphatidylinositol 3-Kinases / genetics, metabolism Recombinant Proteins / chemistry, genetics, metabolism |
| Chemical | |
Reg. No./Substance:
|
0/Apoptosis Regulatory Proteins; 0/BECN1 protein, human; 0/Becn1 protein, mouse; 0/Interleukin-3; 0/Membrane Proteins; 0/Recombinant Proteins; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 3.4.22.-/Caspases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Loss of protein kinase C delta alters mammary gland development and apoptosis.
Next Document: Cytotoxicity of apigenin on leukemia cell lines: implications for prevention and therapy.