Nat. Rev. Urol. doi:10.1038/nrurol.2017.144 Figure 3 WNT signalling regulation by RNF43, ZNRF3, and R-spondin (RSPO) Figure 3 | WNT signalling regulation by RNF43, ZNRF3, and R-spondin (RSPO). RNF43 and ZNRF3 ubiquitin ligases inhibit WNT signalling by ubiquitylating frizzled (FZD) receptors, promoting their degradation. RSPO binds RNF43 and/or ZNRF3 and leucine-rich repeat-containing G protein-coupled receptors (LGR), resulting in membrane clearance of RNF43 and ZNRF3 and increased FZD stability. Mutations in RNF43 and ZNRF3 or overexpression of RSPO as a result of a RSPO gene fusion activate WNT signalling. APC, adenomatous polyposis coli protein; β-cat, β-catenin; CK1, casein kinase 1; GSK, glycogen synthase kinase; LRP, low-density lipoprotein receptor; TCF, T-cell factor; TAZ, transcriptional co-activator with PDZ-binding motif; YAP, yes-associated protein. Murillo-Garzón, V. & Kypta, R. (2017) WNT signalling in prostate cancer Nat. Rev. Urol. doi:10.1038/nrurol.2017.144