E3 ubiquitin-protein ligase RNF166 (RNF166)

E3 ubiquitin-protein ligase RNF166 is a member of the RING finger E3 ligase family, characterized by the presence of a RING domain, a zinc finger domain, and a ubiquitin-interacting motif (UIM)[1][4][5]. RNF166 promotes ubiquitination of multiple substrates, thereby regulating diverse biological processes including apoptosis, antiviral and antibacterial immune responses, and autophagic targeting of intracellular pathogens[1][2][4][5]. In the context of viral infection, RNF166 enhances RNA virus-triggered interferon-β production by facilitating the ubiquitination of TRAF3 and TRAF6, key signaling adaptors in the retinoic acid-inducible gene I-like receptor (RLR) pathway[1]. RNF166 also catalyzes K29- and K33-linked polyubiquitination of autophagy adaptor p62, facilitating antibacterial xenophagy[2]. Dysregulation or overexpression of RNF166 is implicated in cancer, especially colorectal cancer, where it promotes cell proliferation, survival, and migration[3]. RNF166 is of growing interest as a therapeutic target but has no known specific pharmacological inhibitors at present.

Other names

RNF166Ring finger protein 166MGC2647MGC14381RING-type E3 ubiquitin transferase RNF166

Not established for RNF166 specifically; general E3 ligase inhibitors block ubiquitination activity, affecting substrate stability, signal transduction, and cell fate decisions