期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 295, 期 50, 页码 17349-17364出版社
ELSEVIER
DOI: 10.1074/jbc.REV120.009132
关键词
transporter; membrane trafficking; intracellular processing; protein degradation; glycosylation; phosphorylation; oligomerization; ubiquitylation (ubiquitination); protein phosphorylation; drug transporters; organic anion transporters; organic anion-transporting polypeptides
资金
- National Research Foundation of Korea [NRF-2020K2A9A2A08000172]
- Creative-Pioneering Researchers Program through Seoul National University
The organic anion transporters (OATs) and organic anion-transporting polypeptides (OATPs) belong to the solute carrier (SLC) transporter superfamily and play important roles in handling various endogenous and exogenous compounds of anionic charge. The OATs and OATPs are often implicated in drug therapy by impacting the pharmacokinetics of clinically important drugs and, thereby, drug exposure in the target organs or cells. Various mechanisms (e.g. genetic, environmental, and disease-related factors, drug-drug interactions, and food-drug interactions) can lead to variations in the expression and activity of the anion drug-transporting proteins of OATs and OATPs, possibly impacting the therapeutic outcomes. Previous investigations mainly focused on the regulation at the transcriptional level and drug-drug interactions as competing substrates or inhibitors. Recently, evidence has accumulated that cellular trafficking, post-translational modification, and degradation mechanisms serve as another important layer for the mechanisms underlying the variations in the OATs and OATPs. This review will provide a brief overview of the major OATs and OATPs implicated in drug therapy and summarize recent progress in our understanding of the post-translational modifications, in particular ubiquitination and degradation pathways of the individual OATs and OATPs implicated in drug therapy.
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