E3 ubiquitin-protein ligase RNF34 (RNF34)

E3 ubiquitin-protein ligase RNF34 is an enzyme that catalyzes the ubiquitination and subsequent proteasomal degradation of several key cellular proteins, including caspase-8, caspase-10, p53, RIPK1, and others. It is characterized by a RING finger domain enabling its E3 ligase function. RNF34 acts as a negative regulator of apoptosis (by degrading apoptosis-inducing proteins) and modulates immune responses (including type I IFN production) by targeting signaling intermediates such as TBK1 and IRF3 for degradation. In cancer, RNF34 contributes to resistance to cell death and modulates tumor suppressor p53 activity; in viral infection, some viruses exploit RNF34 to suppress host antiviral responses. Its involvement in multiple pathways makes it a potential therapeutic target for cancer, infectious diseases, and disorders of apoptosis or immunity.

Other names

Ring finger protein 34RIFRIFFHuman RING finger homologous to inhibitor of apoptosis proteinRing finger protein 34, E3 ubiquitin protein ligaseCaspases-8 and -10-associated RING finger protein 1RING-type E3 ubiquitin transferase RNF34Caspase regulator CARP1Ring finger protein RIFF

RNF34 mediates proteasomal degradation of target proteins via polyubiquitination (K27- and K48-linked chains). It suppresses apoptotic signaling by degrading caspases 8 and 10, and suppresses p53 tumor suppressor activity by promoting its degradation. Furthermore, it suppresses type I interferon response (antiviral) via ubiquitination and degradation of TBK1 and IRF3, a mechanism often used by viruses for immune evasion.