Journal
ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE
Volume 3, Issue -, Pages 399-425Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev.pathmechdis.3.121806.151434
Keywords
protein misfolding; unfolded protein response; IRE1; PERK; ATF-6
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Funding
- Howard Hughes Medical Institute Funding Source: Medline
- NEI NIH HHS [K08 EY018313-01, K08 EY018313, R01 EY020846] Funding Source: Medline
- NATIONAL EYE INSTITUTE [R01EY020846, K08EY018313] Funding Source: NIH RePORTER
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The endoplasmic reticulum (ER) is the site of synthesis and folding of membrane and secretory proteins, which, collectively, represent a large fraction of the total protein output of a mammalian cell. Therefore; the protein flux through the ER must be carefully monitored for abnormalities, including the buildup of misfolded proteins. Mammalian cells have. evolved an intricate set of signaling pathways from the ER to the cytosol and nucleus, to allow the cell to respond to the of fold presence misfold proteins within the ER. These pathways, known collectively as-the unfolded protein response, are important for normal cellular homeostasis and organismal development and may also play key roles in the pathogenesis of many diseases. This review provides background information on the unfolded protein response and discusses a selection of diseases whose pathogenesis involves ER stress.
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