Related Experiment Video
Updated: Mar 11, 2026

Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity
Published on: June 14, 2024
Unconjugated secondary bile acids activate the unfolded protein response and induce golgi fragmentation via a
Ruchika Sharma1,2, Francis Quilty1,2, John F Gilmer2
1Department of Clinical Medicine, Institute of Molecular Medicine, Trinity Centre for Health Science, St James's Hospital, D08W9RT, Ireland.
Abstract:
Bile acids are components of gastro-duodenal refluxate and regarded as causative agents in oesophageal disease but the precise mechanisms are unknown. Here we demonstrate that a specific subset of physiological bile acids affect the protein secretory pathway by inducing ER stress, activating the Unfolded Protein Response (UPR) and causing disassembly of the Golgi apparatus in oesophageal cells. Deoxycholic acid (DCA), Chemodeoxycholic acid (CDCA) and Lithocholic acid (LCA) activated the PERK arm of the UPR, via phosphorylation of eIF2α and up-regulation of ATF3, CHOP and BiP/GRP78. UPR activation by these bile acids is mechanistically linked with Golgi fragmentation, as modulating the UPR using a PERK inhibitor (GSK2606414) or salubrinal attenuated bile acid-induced effects on Golgi structure. Furthermore we demonstrate that DCA, CDCA and LA activate Src kinase and that inhibition of this kinase attenuated both bile acid-induced BiP/GRP78 expression and Golgi fragmentation. This study highlights a novel mechanism whereby environmental factors (bile acids) impact important cellular processes regulating cell homeostasis, including the UPR and Golgi structure, which may contribute to cancer progression in the oesophagus.
Related Concept Videos
The Unfolded Protein Response
Regulation of the Unfolded Protein Response
Export of Misfolded Proteins out of the ER
Protein Folding Quality Check in the RER
GPI Anchoring of Proteins in the ER Membrane
GPI-anchor structure
A sequence of 11 enzymatic reactions results in the synthesis of the complete GPI anchor consisting of a hydrophobic and a hydrophilic portion. The hydrophobic portion comprises phosphatidylinositol, while the hydrophilic part comprises polar groups like phosphoethanolamine,...
Post-translational Translocation of Proteins to the RER
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...

