title: Posttranscriptional regulation of uridine diphosphate glucuronosyltransferases.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: University of British Columbia, Faculty of Pharmaceutical Sciences , 2405 Wesbrook Mall, Vancouver, BC V6T 1Z3 , Canada +1 604 827 2380 ; abby.collier@ubc.ca.
authors: Zoe
authors: Z
authors: Riches
authors: Abby C
authors: AC
authors: Collier
mesh_terms: D000494:Allosteric Regulation; D001692:Biological Transport; D004721:Endoplasmic Reticulum / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012323:RNA Processing, Post-Transcriptional
chemical_list: D004364:Pharmaceutical Preparations; D014453:Glucuronosyltransferase
keywords: conjugation; drug metabolism; enzyme activity; glucuronidation; glycosylation; phosphorylation