Background: UDP-glucuronosyltransferases (UGTs) are a class of important phase II drug metabolizing
enzymes (DMEs), playing essential roles in the homeostasis of endobiotics as well as the dispositional behavior of
exogenous compounds. The expression and enzyme activity of UGTs are regulated by multiple dimensions of
mechanisms and can be influenced by diverse factors. Thus, the intensive research of its regulatory network is pivotal
for better understanding about the physiological, pathological, and therapeutic significance of UGTs. Despite the lag
to the research in cytochrome P450s, extensive efforts have been made to advance the understanding of the regulatory
network of UGTs in recent years.
Method: This review presents a comprehensive summary and intensive discussion about the recent advancement on
the regulatory network of UGTs.
Results: UGTs can be regulated at the epigenetic level via DNA methylation and histone modification. Various
nuclear receptors can influence the mRNA levels of UGTs in a ligand dependent manner. Some general transcriptional
factors such as AP-1, NF-κB, and p53, and some tissue specific transcriptional factors including HFN1α and
HNF4α can also regulate UGTs at the transcriptional level. Multiple miRNAs have been found to be involved in the
regulation of UGTs at post-transcriptional level. UGT proteins can be directly regulated via various post-translational
modifications, protein-protein interactions, and protein-chemicals interactions, leading to the alternation of enzyme
Conclusion: In addition to the well-defined genetic polymorphism that induce individual variation of UGTs, this
review reinforces the importance of other mechanisms that are critical for the regulation of UGTs.