Ubiquilin-4 (UBQLN4)

Ubiquilin-4 (UBQLN4) is a member of the ubiquilin family of ubiquitin-like proteins that functions as a proteasomal shuttle factor and adaptor in several protein quality control pathways. UBQLN4 is critical for maintaining genomic stability via regulation of DNA double-strand break repair: it is phosphorylated by ATM kinase upon DNA damage, binds to and promotes the degradation of the homologous recombination factor MRE11, thereby curtailing homologous recombination and directing DNA repair toward non-homologous end joining. Additionally, UBQLN4 interacts with the autophagy machinery and participates in autophagosome maturation, and it governs the degradation of misfolded transmembrane domain proteins. UBQLN4 acts as a tumor suppressor by promoting cell cycle arrest and cellular senescence, at least in part by stabilizing the cell cycle inhibitor p21 through downregulation of the E3 ligase RNF114. It is expressed in multiple cellular compartments, including the nucleus, ER, and sites of DNA damage. Downregulation or mutations of UBQLN4 are linked to increased genomic instability and cancer development, particularly gastric cancer, and may have roles in other disease contexts involving DNA repair and protein homeostasis.

Other names

UBQLN4C1orf6CIP75A1UpA1UUBINConnexin43-interacting protein of 75 kDaataxin-1 interacting ubiquitin-like proteinataxin-1 ubiquitin-like-interacting protein A1UAtaxin-1 ubiquitin-like interacting proteinCx43-interacting protein of 75 kDa

Not applicable to current approved drugs. Biological mechanism includes regulating proteasomal protein degradation, modulating DNA damage repair pathway choice, and stabilizing cell cycle inhibitor p21 via inhibition of E3 ubiquitin ligase RNF114.