Ring finger protein 6 (RNF6)

Ring finger protein 6 (RNF6) is an E3 ubiquitin-protein ligase characterized by a C-terminal RING-H2 finger domain responsible for its ligase activity and an N-terminal coiled-coil domain. RNF6 mediates the ubiquitination of specific substrates, thereby regulating their stability, localization, or activity, which can result in protein degradation or functional modulation. While originally considered a potential tumor suppressor, RNF6 is now understood to act as an oncogene, promoting tumor growth and progression through the regulation of critical pathways including SHP1/STAT3, AKT/mTOR, Wnt/β-catenin, and ERα/Bcl-xL, among others. It interacts with and ubiquitinates key regulator proteins such as p53 and SHP1, modulating processes central to carcinogenesis in multiple tissues, including colorectal, prostate, gastric, breast, leukemia, and other cancers. RNF6 may also serve as a transcriptional regulator, for instance upregulating SF3B2 in colorectal cancer. Due to its diverse oncogenic roles and correlation with patient outcome, RNF6 is investigated as a prognostic biomarker and a therapeutic target, though its full range of physiological and pathological functions is not yet fully elucidated.

Other names

E3 ubiquitin-protein ligase RNF6SPG2DKFZp686P0776RING-H2 protein RNF-6RING-type E3 ubiquitin transferase RNF6ring finger protein (C3H2C3 type) 6

Inhibitors block RNF6-mediated ubiquitination, reducing degradation of tumor suppressors or stabilizing negative regulators of proliferative pathways. Some compounds target the RNF6-SF3B2 pathway or disrupt RNF6-driven activation of oncogenic transcriptional programs. Knockdown or inhibition leads to stabilization of tumor suppressors (e.g., p53, SHP1), suppression of key oncogenic pathways (e.g., STAT3, Wnt/β-catenin).