E3 ubiquitin-protein ligase RNF146 (RNF146)

E3 ubiquitin-protein ligase RNF146 (RNF146) is an enzyme in the RING finger protein family that functions as a PAR-binding, ubiquitin ligase (E3 ligase). It specifically recognizes poly-ADP-ribosylated (PARsylated) substrates via its WWE domain, and mediates their ubiquitination and subsequent proteasomal degradation. RNF146 regulates several biological processes, notably the canonical Wnt signaling pathway through degradation of PARsylated Axin and tankyrase proteins, making it a positive regulator of Wnt signaling. It contributes to cell survival, DNA damage responses, and is neuroprotective by blocking parthanatos (PAR-induced cell death). Dysregulation or genetic alteration of RNF146 has been implicated in cancer, neurodegenerative disorders, and other pathogenic processes. RNF146 is located in the cytosol, nucleoplasm, and at the plasma membrane, and acts as a single-subunit, RING-type E3 ligase essential for targeted ubiquitin-mediated protein degradation in human cells.

Other names

Ring finger protein 146DKFZp434O1427dactylidindJ351K20.1IdunaRNF146RING-type E3 ubiquitin transferase RNF146

Drugs targeting the RNF146 axis may act by inhibiting PARsylation-dependent ubiquitination of proteins, thereby regulating Wnt signaling and protein turnover. Potential modulation of tankyrase activity, impacting RNF146-mediated degradation of Axin and β-catenin pathways.