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Table 1 The target and mechanism of A20 regulating arthritis

From: A20: a master regulator of arthritis

Target Pro-inflammation approach Effect of A20 Consequence
NF-κB Trigger the formation of numerous pro-inflammatory cytokines like IFN-γ, TNF-α, IL-1β, IL-6 Restrict its activation Reduced pro-inflammation cytokines
Casp1 Cell pyroptosis Lower activation of Casp1 and inhibit pyroptosis dependent on Casp1 Cell survival and secretion of cytokines is blocked
NLRP3 activation, IL-1 and IL-18 secretion Downregulate the transcription of NLRP3, ASC, procaspase1, proIL-1, and IL-18 Inhibited NLRP3 assembly and activation
RIPK1 Activation of NF-κB Remove K63-linked ubiquitin chains from RIPK1 and add K48-linked ubiquitin on RIPK1 Degradation of RIPK1
Substrate of Casp8
MAPKs Secretion of IL-17A Deubiquitination of TRAF6 and prevent the prolonged phosphorylation of JNK Blocked IL-17 production
Unphosphorylated RIPK3 Macrophages necroptosis Reduce phosphorylation of RIPK3 Macrophages survived
TNFR1 signal complexes Macrophages necroptosis Protect these complexes from being degraded through ZnF7 domain Macrophages survived