Posttranscriptional regulation of uridine diphosphate glucuronosyltransferases

The uridine diphosphate (UDP)-glucuronosyltransferase (UGT) superfamily of enzymes (EC 2.4.1.17) conjugates glucuronic acid to an aglycone substrate to make them more polar and readily excreted. In general, this reaction terminates the activities of chemicals, drugs and toxins, although occasionally a more active or toxic species is produced.

In addition to their well-known transcriptional responsiveness, UGTs are also regulated by posttranscriptional mechanisms. Here, the authors review these mechanisms, including latency, modulation of co-substrate accessibility and binding, dimerization and oligomerization, protein-protein interactions, allosteric inhibition and activation, posttranslational structural and functional modifications and developmental switching for UGTs.

Posttranscriptional regulation of UGTs has traditionally received less attention than nuclear regulation, in part because mechanisms involving ribosomes and endoplasmic reticula are challenging to investigate. Most promising of the posttranscriptional mechanisms reviewed are likely to be effects on co-substrate (UDP-glucuronic acid) transport and availability and structure-function changes to UGT proteins through, for example, glycosylation and phosphorylation. Although classical biochemistry continues to illuminate many aspects of UGT function, advances in proteomics and structural biology are beginning to assist in the determination of posttranscriptional regulation mechanisms for UGTs.