Mechanisms of TNF-independent RIPK3-mediated cell death
- PMID: 36240069
- PMCID: PMC9704539
- DOI: 10.1042/BCJ20210724
Mechanisms of TNF-independent RIPK3-mediated cell death
Abstract
Apoptosis and necroptosis regulate many aspects of organismal biology and are involved in various human diseases. TNF is well known to induce both of these forms of cell death and the underlying mechanisms have been elaborately described. However, cells can also engage apoptosis and necroptosis through TNF-independent mechanisms, involving, for example, activation of the pattern recognition receptors Toll-like receptor (TLR)-3 and -4, or zDNA-binding protein 1 (ZBP1). In this context, cell death signaling depends on the presence of receptor-interacting serine/threonine protein kinase 3 (RIPK3). Whereas RIPK3 is required for TNF-induced necroptosis, it mediates both apoptosis and necroptosis upon TLR3/4 and ZBP1 engagement. Here, we review the intricate mechanisms by which TNF-independent cell death is regulated by RIPK3.
Keywords: RIPK3; apoptosis; cell death; immunology; inflammation; necroptosis.
© 2022 The Author(s).
Conflict of interest statement
The authors declare that there are no competing interests associated with this manuscript. D.R.G. consults for Inzen Pharnaceuticals, Ventus Pharmaceuticals, and Boehringer-Ingleheim.
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