E3 ubiquitin-protein ligase RNF139 (RNF139)

E3 ubiquitin-protein ligase RNF139 (abbreviated as RNF139, also known as TRC8) is a multi-membrane-spanning protein containing a RING-H2 zinc finger domain localized in the endoplasmic reticulum, where it confers E3 ubiquitin ligase activity[1][3][4]. RNF139 regulates cell proliferation and death through ubiquitin-mediated degradation of substrate proteins, playing a key role in cell cycle arrest, lipid metabolism, and protein homeostasis[1][4][6]. In cancer, RNF139 is frequently disrupted by chromosomal translocations (e.g., t(3:8)), particularly in hereditary renal and thyroid cancers[1][3]. Functionally, RNF139 acts as a tumor suppressor, with loss or downregulation promoting cell proliferation and invasion, especially demonstrated in tongue and renal carcinomas[2]. It is implicated in the regulation of AKT and SREBP signaling pathways and may interact with proteins like VHL, COPS5/JAB1, and eIF3 subunits[1][2][6]. Therapeutic targeting is theoretically complex due to broad regulatory functions and the risk of disturbing essential cellular pathways.

Other names

TRC8RCA1HRCA1RING finger protein 139RING-type E3 ubiquitin transferase RNF139Translocation in renal carcinoma on chromosome 8 proteinpatched-related protein translocated in renal cancermultiple membrane spanning receptor TRC8

Induces polyubiquitination and proteasomal degradation of substrate proteins (e.g., HMG-CoA reductase, INSIG1, possibly tumor suppressors). Negative regulation of SREBP processing and lipid metabolism. Suppresses cancer cell proliferation and invasion via ubiquitin-mediated signaling pathway modulation.