E3 ubiquitin-protein ligase Arkadia (RNF111)

Ring finger protein 111 (E3 ubiquitin-protein ligase Arkadia) is a nuclear enzyme containing a RING finger domain, operating as an E3 ubiquitin ligase. It promotes the ubiquitination and proteasomal degradation of negative regulators of the TGF-beta/Nodal pathway, such as Smad7, c-Ski, and SnoN, enhancing transcriptional activation and facilitating embryonic development, hematopoietic stem/progenitor cell maintenance, and cellular responses to DNA damage. Arkadia also acts as a SUMO-targeted ubiquitin ligase (STUbL), targeting polysumoylated proteins for degradation, with important functions in tissue fibrosis, cancer progression, and hematopoiesis. Dysfunction or altered regulation of RNF111 may contribute to cancer, fibrotic disease, hematological defects, and impaired DNA repair.

Other names

ArkadiaRNF111RING finger protein 111

Drugs targeting RNF111/Arkadia would typically act via inhibition of E3 ligase activity, modulating ubiquitination, proteasomal degradation, altering TGF-beta/Nodal signaling, or impacting SUMO-mediated protein turnover