Dec 18, 2004

ER stress and the unfolded protein response

Mutation Research
Martin Schröder, Randal J Kaufman


Conformational diseases are caused by mutations altering the folding pathway or final conformation of a protein. Many conformational diseases are caused by mutations in secretory proteins and reach from metabolic diseases, e.g. diabetes, to developmental and neurological diseases, e.g. Alzheimer's disease. Expression of mutant proteins disrupts protein folding in the endoplasmic reticulum (ER), causes ER stress, and activates a signaling network called the unfolded protein response (UPR). The UPR increases the biosynthetic capacity of the secretory pathway through upregulation of ER chaperone and foldase expression. In addition, the UPR decreases the biosynthetic burden of the secretory pathway by downregulating expression of genes encoding secreted proteins. Here we review our current understanding of how an unfolded protein signal is generated, sensed, transmitted across the ER membrane, and how downstream events in this stress response are regulated. We propose a model in which the activity of UPR signaling pathways reflects the biosynthetic activity of the ER. We summarize data that shows that this information is integrated into control of cellular events, which were previously not considered to be under control of ER signa...Continue Reading

Mentioned in this Paper

PPP1R15B gene
Metabolic Process, Cellular
Establishment and Maintenance of Localization
ISYNA1 gene
ATF3 gene
Biochemical Pathway
Proteasome Pathway
Cyclic AMP-Responsive DNA-Binding Protein

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