Related Experiment Video
Updated: Nov 8, 2025

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
Nuclear receptors FXR and SHP regulate protein N-glycan modifications in the liver
Bhoomika Mathur1, Asif Shajahan2, Waqar Arif3
1Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Abstract:
Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. Here, we report a previously unknown function for the hepatic FXR-SHP axis in controlling protein N-linked glycosylation. Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. This up-regulation of N-glycosylation machinery was specific to the Golgi apparatus and not the endoplasmic reticulum. The increased glycan complexity in the LDKO correlated well with dilated unstacked Golgi ribbons and alterations in the secretion of albumin, cholesterol, and triglycerides. Our findings demonstrate a role for the FXR-SHP axis in maintaining glycoprotein diversity in the liver.
Related Concept Videos
Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Regulation of Nuclear Protein Sorting
Protein Modifications in the RER
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
Cell Specific Gene Expression
Signal Transduction: Overview
Typically, signal transduction involves three...
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...

