» Articles » PMID: 39478961

Retinoid X Receptor Heterodimers in Hepatic Function: Structural Insights and Therapeutic Potential

Overview
Journal Front Pharmacol
Date 2024 Oct 31
PMID 39478961
Authors
Affiliations
Soon will be listed here.
Abstract

Nuclear receptors (NRs) are key regulators of multiple physiological functions and pathological changes in the liver in response to a variety of extracellular signaling changes. Retinoid X receptor (RXR) is a special member of the NRs, which not only responds to cellular signaling independently, but also regulates multiple signaling pathways by forming heterodimers with various other NR. Therefore, RXR is widely involved in hepatic glucose metabolism, lipid metabolism, cholesterol metabolism and bile acid homeostasis as well as hepatic fibrosis. Specific activation of particular dimers regulating physiological and pathological processes may serve as important pharmacological targets. So here we describe the basic information and structural features of the RXR protein and its heterodimers, focusing on the role of RXR heterodimers in a number of physiological processes and pathological imbalances in the liver, to provide a theoretical basis for RXR as a promising drug target.

References
1.
Jin X, Peng D, Kim S, Kim N, Nejad J, Kim D . Vitamin A supplementation downregulates and mRNA expression in weaned beef calves. Anim Nutr. 2022; 10:372-381. PMC: 9356019. DOI: 10.1016/j.aninu.2022.06.007. View

2.
Chandra V, Huang P, Hamuro Y, Raghuram S, Wang Y, Burris T . Structure of the intact PPAR-gamma-RXR- nuclear receptor complex on DNA. Nature. 2008; 456(7220):350-6. PMC: 2743566. DOI: 10.1038/nature07413. View

3.
Lebovitz H . Thiazolidinediones: the Forgotten Diabetes Medications. Curr Diab Rep. 2019; 19(12):151. PMC: 6881429. DOI: 10.1007/s11892-019-1270-y. View

4.
Luo J, Yang H, Song B . Mechanisms and regulation of cholesterol homeostasis. Nat Rev Mol Cell Biol. 2019; 21(4):225-245. DOI: 10.1038/s41580-019-0190-7. View

5.
Leid M, Kastner P, Lyons R, Nakshatri H, Saunders M, Zacharewski T . Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently. Cell. 1992; 68(2):377-95. DOI: 10.1016/0092-8674(92)90478-u. View