The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index.
Autophagosomal Membrane Serves as Platform for Intracellular Death-inducing Signaling Complex (iDISC)-mediated Caspase-8 Activation and Apoptosis
Open accessAbstract
Autophagy and apoptosis are two evolutionarily conserved processes that regulate cell fate in response to cytotoxic stress. However, the functional relationship between these two processes remains far from clear. Here, we demonstrate an autophagy-dependent mechanism of caspase-8 activation and initiation of the apoptotic cascade in response to SKI-I, a pan-sphingosine kinase inhibitor, and bortezomib, a proteasome inhibitor. Autophagy is induced concomitantly with caspase-8 activation, which is responsible for initiation of the caspase cascade and the mitochondrial amplification loop that is required for full execution of apoptosis. Inhibition of autophagosome formation by depletion of Atg5 or Atg3 results in a marked suppression of caspase-8 activation and apoptosis. Although caspase-8 self-association depends on p62/SQSTM1, its self-processing requires the autophagosomal membrane. Caspase-8 forms a complex with Atg5 and colocalizes with LC3 and p62. Moreover, FADD, an adaptor protein for caspase-8 activation, associates with Atg5 on Atg16L- and LC3-positive autophagosomal membranes and loss of FADD suppresses cell death. Taken together, these results indicate that the autophagosomal membrane serves as a platform for an intracellular death-inducing signaling complex (iDISC) that recruits self-associated caspase-8 to initiate the caspase-8/-3 cascade.
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Cites
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“Taken together, these results suggest that the recruitment and activation of caspase-8 in response to SKI-I occurs not only in a p62 LC3-II-dependent manner but also through the association of Atg5 FADD at the autophagosomal membrane.”
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Cited by
Self-consumption: the interplay of autophagy and apoptosis
Mariño, G., Niso-Santano, M., Baehrecke, E. H., & Kroemer, G. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3735 · Cited by 2,172
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Autophagy and apoptosis: where do they meet?
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Metadata
- Authors
- Young, M. M., Takahashi, Y., Khan, O., Park, S., Hori, T., Yun, J., Sharma, A. K., Amin, S., Hu, C.-D., Zhang, J., Kester, M., & Wang, H.-G.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2012-04
- Volume
- 287
- Issue
- 15
- Pages
- 12455-12468
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1992637754
- Cited by
- 372
- References
- 62
- FWCI
- 11.50
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Young, M. M., Takahashi, Y., Khan, O., Park, S., Hori, T., Yun, J., Sharma, A. K., Amin, S., Hu, C.-D., Zhang, J., Kester, M., & Wang, H.-G. (2012). Autophagosomal Membrane Serves as Platform for Intracellular Death-inducing Signaling Complex (iDISC)-mediated Caspase-8 Activation and Apoptosis. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m111.309104
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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