RING finger protein 4 (RNF4)

RING finger protein 4 (RNF4) is a RING-type E3 ubiquitin ligase that acts as a SUMO-targeted ubiquitin ligase (STUbL) in humans[1][2][3][4][5][6]. RNF4 contains a RING finger domain responsible for E3 ligase activity and multiple SUMO-interacting motifs that enable it to specifically recognize and polyubiquitylate proteins modified by SUMO (small ubiquitin-like modifier), targeting them for proteasomal degradation. RNF4 plays a crucial role in the DNA damage response by promoting the repair of DNA double-strand breaks through homologous recombination and non-homologous end joining[3][5][6]. It orchestrates the turnover of DNA repair factors at sites of damage, and its deficiency leads to persistent DNA lesions, genome instability, and impaired spermatogenesis. RNF4 is also a key mediator of the therapeutic action of arsenic trioxide in acute promyelocytic leukemia, by facilitating the degradation of SUMOylated PML. Its molecular functions center on integrating the SUMO and ubiquitin pathways to maintain protein homeostasis, genome integrity, and cellular response to genotoxic stress[2][4][6].

Other names

SNURFRES4-26Protein SNURFSLX5Small nuclear ring finger proteinE3 ubiquitin-protein ligase RNF4E3 ubiquitin ligase RNF4RING-type E3 ubiquitin transferase RNF4small nuclear RING finger protein

Degradation of SUMOylated proteins (e.g., PML) via ubiquitin-proteasome pathway (as part of arsenic trioxide mechanism in leukemia)