Drug transporter proteins are critical to the distribution of a wide range of endogenous compounds and xenobiotics such as hormones, bile acids, peptides, lipids, sugars, and drugs. There are two classes of drug transporters– the solute carrier (SLC) transporters and ATP-binding cassette (ABC) transporters –which predominantly differ in the energy source utilized to transport substrates across a membrane barrier. Despite their hydrophobic nature and residence in the membrane bilayer, drug transporters have dynamic structures and adopt many conformations during the translocation process. Whereas there is significant literature evidence for the substrate specificity and structure-function relationship for clinically relevant drug transporters proteins, there is less of an understanding in the regulatory mechanisms that contribute to the functional expression of these proteins. Post-translational modifications have been shown to modulate drug transporter functional expression via a wide range of molecular mechanisms. These modifications commonly occur through the addition of a functional group (e.g. phosphorylation), a small protein (e.g. ubiquitination), sugar chains (e.g. glycosylation), or lipids (e.g. palmitoylation) on solvent accessible amino acid residues. These covalent additions often occur as a result of a signaling cascade and may be reversible depending on the type of modification and the intended fate of the signaling event. Here, we review the significant role in which post-translational modifications contribute to the dynamic regulation and functional consequences of SLC and ABC drug transporters and highlight recent progress in understanding their roles in transporter structure, function, and regulation.
|Number of pages||12|
|Journal||Pharmacology and Therapeutics|
|State||Published - Dec 2018|
Bibliographical noteFunding Information:
This work was funded in part by a grant from the National Institutes of Health, NIDDK award #DK61425 (to PWS).
This work was funded in part by a grant from the National Institutes of Health , NIDDK award # DK61425 (to PWS).
© 2018 Elsevier Inc.
- Membrane transport
- Post-translational modification
ASJC Scopus subject areas
- Pharmacology (medical)