E3 ubiquitin-protein ligase RNF123 (RNF123)

E3 ubiquitin-protein ligase RNF123 (RNF123) is an enzyme characterized by a C-terminal RING finger domain and an N-terminal SPRY domain, functioning as a component of the Kip1 ubiquitination-promoting complex (with KPC2) to target key cell cycle inhibitors such as p27/Kip1 for proteasomal degradation at the G0-G1 cell cycle transition[4][2][1]. RNF123 also regulates the NF-κB pathway through ubiquitination of NFKB1 (p105), facilitating its maturation to the active p50 subunit[4][2]. Independent of its E3 ligase activity, RNF123 has a critical role in innate immunity as a negative regulator of antiviral signaling mediated by the RIG-I and MDA5 cytoplasmic RNA sensors, inhibiting interferon-beta (IFN-β) production during viral infection[1][5][4]. Its activity influences cell cycle progression, immunity, and has implications in cancer and muscular dystrophy states. Alternative splicing results in several transcript variants, and its dysfunction or dysregulation may play roles in disease states, but no direct drugs against RNF123 are currently reported.

Other names

RING finger protein 123KPC1Kip1 ubiquitination-promoting complex protein 1Kip1 ubiquitination-promoting complex subunit 1FP1477FLJ12565RING-type E3 ubiquitin transferase RNF123

Drugs targeting RNF123 (hypothetical, as none currently known): inhibition or modulation of E3 ligase activity, alteration of cell cycle progression, suppression or enhancement of innate immune signaling.