Document Type
Article
Publication Date
1-3-2017
Abstract
Apoptosis is a genetically regulated cell suicide programme mediated by activation of the effector caspases 3, 6 and 7. If apoptotic cells are not scavenged, they progress to a lytic and inflammatory phase called secondary necrosis. The mechanism by which this occurs is unknown. Here we show that caspase-3 cleaves the GSDMD-related protein DFNA5 after Asp270 to generate a necrotic DFNA5-N fragment that targets the plasma membrane to induce secondary necrosis/pyroptosis. Cells that express DFNA5 progress to secondary necrosis, when stimulated with apoptotic triggers such as etoposide or vesicular stomatitis virus infection, but disassemble into small apoptotic bodies when DFNA5 is deleted. Our findings identify DFNA5 as a central molecule that regulates apoptotic cell disassembly and progression to secondary necrosis, and provide a molecular mechanism for secondary necrosis. Because DFNA5-induced secondary necrosis and GSDMD-induced pyroptosis are dependent on caspase activation, we propose that they are forms of programmed necrosis.
Recommended Citation
Rogers, Corey; Fernandes-Alnemri, Teresa; Mayes, Lindsey; Alnemri, Diana; Cingolani, Gino; and Alnemri, Emad S., "Cleavage of DFNA5 by caspase-3 during apoptosis mediates progression to secondary necrotic/pyroptotic cell death." (2017). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 111.
https://jdc.jefferson.edu/bmpfp/111
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
28045099
Comments
This article has been peer reviewed. It is the author’s final published version in Nature Communications
Volume 8, January 2017, Article number 14128.
The published version is available at DOI: 10.1038/ncomms14128. Copyright © Rogers et al.