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. 2021 Oct 1;12:727861. doi: 10.3389/fimmu.2021.727861

Figure 1.

Figure 1

Schematic representation of anti-inflammatory activity of MCPIP-1. Binding of molecules (DAMPs) derived from tissue damage or pathogens (PAMPs) to PRRs triggers interactions between the cytoplasmic adaptor proteins and the kinases IRAK. This engages the ubiquitin ligase TRAF6 to make polyubiquitin chains that activate the IKK complex, leading to phosphorylation and subsequent ubiquitination IKBα. This releases P50/p65 dimer for entry into the nucleus to cause transcriptional activation of NFκB-dependent genes encoding inflammatory cytokines. Ubiquitylation of RIP1, and potentially other components of the complex, recruits IKKγ and TAK1 for NFκB and MAPK activation (not shown). MCPIP-1 hydrolyzes all of these K48- and K63-linked polyubiquitins to block NFκB activation. The RNase activity of MCPIP-1 also degrades viral RNA and some mRNAs encoding for inflammatory cytokines, leading to dampening of protein expression of the inflammatory cytokines. The anti-Dicer activity of MCPIP-1 can cleave the terminal loops of pre-miRNAs leading to destabilization of pre-miRNAs and suppression of the miRNA biogenesis.