UDP-glucuronic acid decarboxylase 1 (UXS1) (UXS1)

UDP-glucuronic acid decarboxylase 1 (UXS1), also known as UDP-xylose synthase, is a Golgi-resident enzyme that catalyzes the conversion of UDP-glucuronic acid into UDP-xylose [1, 4]. This enzymatic step is crucial because UDP-xylose is the essential sugar donor for the initiation of glycosaminoglycan (GAG) chains on proteoglycans and for the O-xylosylation of Notch receptors [1, 3]. By regulating the availability of UDP-xylose, UXS1 plays a fundamental role in the assembly of the extracellular matrix and the modulation of cell signaling pathways during development [2]. Mutations in the UXS1 gene are linked to spondyloepimetaphyseal dysplasia, a condition characterized by significant skeletal and connective tissue abnormalities [2]. Although UXS1 is not currently a target for any FDA-approved drugs, it is being investigated for its potential to influence cancer progression and fibrotic diseases through the modification of the tumor microenvironment [1, 2]. Future therapeutic applications may involve small-molecule inhibitors designed to reduce the pathological accumulation of GAGs or to alter Notch-mediated signaling in specific disease contexts [3, 4].

Other names

UDP-xylose synthase 1UDP-glucuronate decarboxylase 1UXS1UGD

Inhibition of the decarboxylation of UDP-glucuronic acid to UDP-xylose, thereby reducing the availability of substrate for glycosaminoglycan synthesis and Notch xylosylation.