In:
eLife, eLife Sciences Publications, Ltd, Vol. 3 ( 2014-04-15)
Abstract:
A protein can only work properly if it has been folded into the correct shape. However, it is estimated that about one third of new proteins have the wrong shape. This is a major challenge for cells because misfolded proteins are often toxic, and cause many neurodegenerative and metabolic disorders. In eukaryotic cells, most protein folding takes place inside a part of the cell called the endoplasmic reticulum (ER). If an incorrectly folded protein is detected, it is prevented from leaving the ER until it is refolded correctly, or destroyed. If too many proteins are misfolded, a process called the unfolded protein response helps the cell to cope with this ‘ER stress’ by expanding the ER and producing more of the molecules that assist protein folding. If this does not relieve the ER stress, the cell self-destructs. Neighboring cells then have to increase protein production to compensate for what would have been produced by the dead cell, thereby increasing the chance that they will also experience ER stress. Activation of a protein called LRH-1 (short for liver receptor homolog-1) that is produced in the liver, pancreas and intestine can relieve the symptoms of the various metabolic diseases that are associated with chronic ER stress, including type II diabetes and fatty liver disease. However, researchers have been puzzled by the fact that although LRH-1 performs many different roles, its molecular structure provides few clues as to how it can do this. Mamrosh et al. now confirm the speculated link between LRH-1 and ER stress relief in mice. LRH-1 triggers a previously unknown pathway that can relieve ER stress and is completely independent of the unfolded protein response. Targeting LRH-1 with certain chemical compounds alters its activity, suggesting that drug treatments could be developed to relieve ER stress. As similar targets for drugs have not been found in the unfolded protein response, the discovery of the LRH-1 pathway could lead to new approaches to the treatment of the diseases that result from ER stress.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.01694.001
DOI:
10.7554/eLife.01694.002
DOI:
10.7554/eLife.01694.003
DOI:
10.7554/eLife.01694.004
DOI:
10.7554/eLife.01694.005
DOI:
10.7554/eLife.01694.006
DOI:
10.7554/eLife.01694.007
DOI:
10.7554/eLife.01694.008
DOI:
10.7554/eLife.01694.009
DOI:
10.7554/eLife.01694.010
DOI:
10.7554/eLife.01694.011
DOI:
10.7554/eLife.01694.012
DOI:
10.7554/eLife.01694.013
DOI:
10.7554/eLife.01694.014
DOI:
10.7554/eLife.01694.015
DOI:
10.7554/eLife.01694.016
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2014
detail.hit.zdb_id:
2687154-3