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. 2021 May 3;22(5):e52970. doi: 10.15252/embr.202152970

Figure 1. The deubiquitinating enzyme USP42 stabilizes RNF43/ZNRF3 at the plasma membrane.

Figure 1

When bound to RSPO and LGR, RNF43/ZNRF3 are removed from the cell surface as a result of auto‐ubiquitination and endocytosis, inhibiting the E3 ligase activity. USP42 counteracts R/Z auto‐ubiquitination, stabilizing their levels on the plasma membrane. Consequently, R/Z are available to inhibit WNT signalling by promoting FZD ubiquitination and endo‐lysosomal degradation. CK1 phosphorylates R/Z cytoplasmic tail, enhancing its anti‐WNT activity. DVL bridges R/Z to FZD, allowing downregulation of the WNT receptors.