RNF114 (also known as Znf313) is a p21(WAF1)-targeting ubiquitin E3 ligase that interacts with X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) and may play a role in p53-mediated cell-fate decisions [, ]. It is involved in immune response to double-stranded RNA in disease pathogenesis []. Moreover, RNF114 interacts with A20 and modulates its ubiquitination []. It negatively regulates nuclear factor-kappaB (NF-kappaB)-dependent transcription and positively regulates T-cell activation []. RNF114 may play a putative role in the regulation of immune responses, since it corresponds to a novel psoriasis susceptibility gene, ZNF313 []. RNF114, together with three closely related proteins: RNF125, RNF138 and RNF166, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM).
This entry includes the C2HC RNF-type zinc finger.Ubiquitination is a post-translational modification that mediates the covalent attachment of ubiquitin (Ub), a small, highly conserved, cytoplasmic protein of 76 amino acid residues, to target proteins. This conjugation is catalyzed by the sequential action of three enzymes: Ub-activating (E1) enzyme, Ub-conjugating (E2) enzyme and Ub ligase (E3). A large number of RING finger (RNF) proteins are present in eukaryotic cells and the majority of them are believed to act as E3 ubiquitin ligases. The closely related proteins RNF125/TRAC-1, RNF114 (also known as Zpf313), RNF138 (or NARF) and RNF166 contain, apart from the RING domain, a C2HC (Cys2-His-Cys)- and two C2H2 (Cys2-His2)-type zinc fingers, as well as an ubiquitin interacting motif (UIM) [, , , ].Some proteins known to contain a C2HC RNF-type zinc finger are listed below:Mammalian RNF125/T-cell RING protein in activation 1 (TRAC-1)/, a positive regulator of T-cell activation. It negatively regulates RIG-1 mediated antiviral activity via conjugating ubiquitin chains to RIG-1 and MDA5, leading to their degradation by the proteasome.Vertebrate RNF114, acts as negative regulator of NF-kappaB-dependent transcription. It interacts with A20 in T cells and modulates A20 ubiquitylation.Vertebrate RNF138, likely involved in regulating homologous recombination repair pathway.Vertebrate RNF166, potentiates the RNA virus-induced production of IFN-beta via enhancing the ubiquitination of TRAF3 and TRAF6.
