MilliporeSigma™ TDO2, Mouse, Unlabeled, Clone: 7A6.1,

Description

• E3 ubiquitin-protein ligase RNF43 (UniProt Q68DV7; also known as RING finger protein 43) is encoded by the RNF43 gene (Gene ID 54894) in human
• RNF43 and the homologous ZNRF3 are cell-surface transmembrane E3 ubiquitin ligases upregulated upon Wnt/ -catenin signaling and act as potent Wnt signaling pathway negative feedback regulators by mediating ubiquitination of Frizzled (FZD) and LRP6 for lysosomal degradation
• RNF43/ZNRF3 activity is counteracted by stem cell growth factor R-spondin that induces membrane ZNRF3/RNF43 clearance by binding ZNRF3/RNF43 and LGR4/LGR5
• Physical interaction with Dishevelled (DVL) is essential for ZNRF3/RNF43 Wnt inhibitory activity, and DVL knockdown significantly increases cell surface levels of FZD and LRP6
• In addition, RNF43 suppresses canonical and noncanonical Wnt signaling via distinct mechanisms
• While interaction between the extracellular protease-associated (PA) domain and the cysteine-rich domain (CRD) of FZD and RNF43 intracellular RING finger domain is necessary for canonical Wnt/ -catenin signaling inhibition, interaction between FZD PDZ domain and RNF43 C-terminal cytoplasmic region is essential for suppressing noncanonical Wnt signaling
• R-spondin overexpression through gene translocation and loss-of-function RNF43/ZNRF3 gene mutations are found in human cancers as means to escape from Wnt signaling negative feedback regulation
• Human RNF43 is produced with a signal peptide (a.a
• 1-23) sequence, which is posttranslationally removed to yiled the mature enzyme with an N-terminal extracellular domain (a.a
• 24-197), a transmembrane domain (a.a
• 198-218), and a large cytoplasmic region (a.a
• 219-783) that contains an atypical RING-type zinc finger (a.a
• 272-313) and a pro-rich (a.a
• 569-760) region.