ABSTRACT
Introduction: Protein-protein interaction and signaling crosstalk contribute to the regulation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR) and broaden their cellular function.
Area covered: This review covers key historic discoveries and recent advances in our understanding of the broad function of PXR and CAR and their regulation by protein-protein interaction and signaling crosstalk.
Expert opinion: PXR and CAR were first discovered as xenobiotic receptors; however, it is clear that PXR and CAR perform a much broader range of cellular functions through protein-protein interaction and signaling crosstalk, which typically mutually affect the function of all the partners involved. Future research on PXR and CAR should, therefore, look beyond their xenobiotic function.
Article highlights
PXR and CAR are well-recognized xenobiotic receptors.
PXR and CAR interact with other proteins.
PXR and CAR crosstalk with other signaling pathways.
Protein-protein interaction and signal crosstalk mutually affect the function of all partners involved.
Investigations of protein-protein interaction and signaling crosstalk reveal the broader cellular functions of PXR and CAR.
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Acknowledgments
The authors thank Keith A. Laycock, PhD for editing the manuscript.
Declaration of interest
This work was supported by the American Lebanese Syrian Associated Charities (ALSAC), St. Jude Children’s Research Hospital, National Institutes of Health National Institute of General Medical Sciences [Grants RO1-GM086415, RO1-GM110034, & R35-GM118041], and National Cancer Institute [Grant P30-CA21765]. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.