RNF4 is a SUMO-targeted E3 ubiquitin-protein ligase with a pivotal function in the DNA damage response (DDR) through interacting with the deubiquitinating enzyme ubiquitin-specific protease 11 (USP11), a known DDR-component, and further facilitating DNA repair []. It plays a novel role in preventing the loss of intact chromosomes and ensures the maintenance of chromosome integrity. Moreover, RNF4 is responsible for the UbcH5A-catalyzed formation of K48 chains that target SUMO-modified promyelocytic leukemia (PML) protein for proteasomal degradation in response to arsenic treatment []. It also interacts with telomeric repeat binding factor 2 (TRF2) in a small ubiquitin-like modifiers (SUMO)-dependent manner and preferentially targets SUMO-conjugated TRF2 for ubiquitination through SUMO-interacting motifs (SIMs) []. Furthermore, RNF4 can form a complex with a Ubc13-ubiquitin conjugate and Ube2V2. It catalyzes K63-linked polyubiquitination by the Ube2V2-Ubc13 (ubiquitin-loaded) complex []. Meanwhile, RNF4 negatively regulates nuclear factor kappa B (NF-kappaB) signaling by down-regulating transforming growth factor beta (TGF-beta)-activated kinase 1 (TAK1)-TAK1-binding protein2 (TAB2) []. RNF4 contains four SIMs followed by a C3HC4-type RING-HC finger at the C-terminal [].This entry represents the C3HC4-type RING-HC finger.
