During tumor necrosis factor (TNF)-induced necroptosis, RIPK3 and RIPK1 associate with each other through their RHIM domains into heteromeric RIPK1:RIPK3 complexes that further polymerize into filamentous β-amyloid structures promoting the activation of RIPK3 kinase (Cho Y et al. 2009; Li J et al. 2012). Functionally active RIPK3 activates mixed-lineage kinase domain-like pseudokinase (MLKL), the membrane-disrupting effector of programmed necrosis (Sun L et al. 2012; Murphy JM et al. 2013; Wang H et al. 2014). Other RHIM-containing proteins, such as the TLR3/TLR4 adaptor TRIF (also known as TICAM1) and the DNA sensor DAI/ZBP can form the necroptotic signaling platforms to support activation of RIPK3 and its interaction with MLKL (Kaiser W et al. 2013; Lin J et al. 2016).
This Reactome event shows a scaffolding role of RIPK3 bound to RIPK1 in supporting the formation of SARS-CoV-1 3a oligomers.
Shi, CS, Hwang, IY, Kehrl, JH, Xiao, X, Kamenyeva, O, Nabar, NR, Yue, Y, Wang, M
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