| 背景 | Receptor-interacting serine/threonine-protein kinase 3 (p-RIPK3) is a ~56 kDa protein. Serine/threonine-protein kinase that activates necroptosis and apoptosis, two parallel forms of cell death. Necroptosis, a programmed cell death process in response to death-inducing TNF family members, is triggered by RIPK3 following activation by ZBP1. Activated RIPK3 forms a necrosis-inducing complex and mediates phosphorylation of MLKL, promoting MLKL localization to the plasma membrane and execution of programmed necrosis characterized by calcium influx and plasma membrane damage. In addition to TNF-induced necroptosis, necroptosis can also take place in the nucleus in response to orthomyxoviruses infection: following ZBP1 activation, which senses double-stranded Z-RNA structures, nuclear RIPK3 catalyzes phosphorylation and activation of MLKL, promoting disruption of the nuclear envelope and leakage of cellular DNA into the cytosol. Also regulates apoptosis: apoptosis depends on RIPK1, FADD and CASP8, and is independent of MLKL and RIPK3 kinase activity. 5. Zhao, J. et al. (2012) Proceedings of the National Academy of Sciences of the United States of America 109, 5322-7. PMID: 224214396. Choi, SW. et al. (2018) Molecular cell 70, 920-935.e7. PMID: 298836097. Ashida, H. et al. (2020) The EMBO journal 39, e104469. PMID: 32657447 |
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