RNF43 (F5H7P) Rabbit Monoclonal Antibody #76589

Ring finger protein 43 (RNF43) is an E3 ubiquitin ligase that serves as a potent negative regulator of the Wnt/β-Catenin signaling pathway by controlling Wnt receptor availability at the cell surface. In its primary cellular role, RNF43 localizes to the plasma membrane where it ubiquitinates the cytoplasmic loops of Frizzled receptors, targeting them for endocytic internalization and subsequent lysosomal degradation (1). RNF43 can itself be targeted for removal from the cell surface through the binding of the ligand R-spondin to its ectodomain, resulting in the formation of a complex that triggers membrane clearance of the E3 ligase (2). Additionally, RNF43 can function within the nucleus to inhibit signaling by sequestering T cell factor 4 (TCF4) to the nuclear membrane and silencing its transcriptional activity (3). RNF43 functions as a tumor suppressor, and its mutational inactivation is a driving event in several malignancies, particularly in colorectal cancer characterized by microsatellite instability (4,5). Because RNF43-mutant tumors depend on Wnt ligands for growth, the presence of RNF43 mutations may serve as a critical predictive biomarker for patient selection in the clinical development of Wnt inhibitors (6). Phosphorylation of RNF43 at a serine triplet was shown to be required for negative regulation of Wnt signaling and suppressed cancer-associated oncogenic RNF43 mutants, suggesting that therapeutic phosphomimetics could restore functional tumor suppressor activity (7). More recently, antibody-based proteolysis-targeting chimeras (PROTACs) have been developed to induce the lysosomal degradation of programmed cell death ligand 1 (PD-L1) via recruitment of RNF43 (8).