E3 ubiquitin-protein ligase RNF126 (RNF126)

E3 ubiquitin-protein ligase RNF126 (RNF126) is an enzyme belonging to the RING finger family, functioning primarily as an E3 ubiquitin ligase[4][7]. RNF126 is involved in the ubiquitination and proteasomal degradation of multiple substrates, including mitochondrial membrane proteins, cell cycle regulators (p21), and tumor suppressors such as PTEN and LKB1[2][3][5]. It plays a critical role in the DNA damage response by suppressing double-strand break repair foci formation and regulating genome integrity, acting as a negative regulator of non-homologous end joining and histone ubiquitination at specific lysine residues on H2A[1]. In the context of cancer, RNF126 acts as an oncogene—promoting cell proliferation, metastasis, and stem cell-like properties, especially by degrading PTEN and LKB1, thereby activating proliferation pathways (PI3K/AKT)[3][5]. RNF126 functions together with chaperones such as BAG6 and UBQLN1 to maintain protein quality control, targeting mislocalized or damaged proteins for degradation[2][4][7]. The expression and activity of RNF126 have been proposed as biomarkers and therapeutic targets in various cancers, but therapeutic interventions require caution due to its roles in normal cell regulation and stress response[5][1][2].

Other names

Ring finger protein 126FLJ20552RING finger protein 126RNF126

Proteasome-mediated degradation: RNF126 ubiquitylates target proteins, directing them for proteasomal degradation Modulation of DNA damage response: negative regulator of focus formation and repair pathways, impacting cell sensitivity to DNA-damaging agents (e.g., cisplatin)