Regulation of Mammalian UDP-glucuronosyltransferases.

Regulation of Mammalian UDP-glucuronosyltransferases. Curr Drug Metab. 2018 Mar 07;: Authors: Wang H, Cao G, Wang G, Hao H Abstract 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. This review presents a comprehensive summary and intensive discussion about the recent advancement on the regulatory network of UGTs. 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 transcriptional level. Multiple miRNAs have been found to be involved in the regulation of UGTs at post-transcriptional level. UGT proteins ...
Source: Current Drug Metabolism - Category: Drugs & Pharmacology Authors: Tags: Curr Drug Metab Source Type: research