E3 ubiquitin-protein ligase RNF25 (RNF25)

E3 ubiquitin-protein ligase RNF25 is a zinc finger/RING finger E3 ubiquitin ligase involved in regulating protein turnover by targeting specific substrates for ubiquitin-mediated degradation[1][5]. It modulates NF-κB signaling by interacting with the p65 (RelA) subunit, playing roles in transcriptional activation linked to cancer, inflammation, and immune response[1][3][5]. RNF25 supports Wnt signaling by interacting with Axin and Nkd proteins[4]. It also protects DNA replication forks under replication stress by recruiting REV7, a process separable from its canonical E3 ligase activity[2]. In disease, RNF25 has emerged as a mediator of cancer progression, drug resistance, and metastasis, particularly through its effects on transcription factors, cytokine induction, and degradation of cell adhesion proteins[1][4][5]. RNF25 serves as a link between ubiquitination, transcriptional regulation, translation quality control, and cellular DNA damage response and is considered a promising but complex therapeutic target in oncology and other diseases[1][2][5]. No direct small molecule inhibitors are currently in clinical use targeting RNF25 as of September 2025.

Other names

AO7FLJ13906RING finger protein 25RING finger protein AO7RNF25E3 ubiquitin-protein ligase RNF25RING-type E3 ubiquitin transferase RNF25ring finger protein AO7

Proteasomal degradation via E3 ubiquitin ligase activity; NF-κB transcriptional modulation; Modulation of Wnt signaling by ubiquitination of Nkd2 and interaction with Axin; Protection of DNA replication forks under replication stress, independently of ubiquitination; Quality control and degradation of translation factors on stalled ribosomes