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Roles of CHOP/GADD153 in endoplasmic reticulum stress.

TLDR
The current understanding of the roles of C/EBP homologous protein (CHOP) and GADD153 in ER stress-mediated apoptosis and in diseases including diabetes, brain ischemia and neurodegenerative disease are summarized.
Abstract
Endoplasmic reticulum (ER) is the site of synthesis and folding of secretory proteins. Perturbations of ER homeostasis affect protein folding and cause ER stress. ER can sense the stress and respond to it through translational attenuation, upregulation of the genes for ER chaperones and related proteins, and degradation of unfolded proteins by a quality-control system. However, when the ER function is severely impaired, the organelle elicits apoptotic signals. ER stress has been implicated in a variety of common diseases such as diabetes, ischemia and neurodegenerative disorders. One of the components of the ER stress-mediated apoptosis pathway is C/EBP homologous protein (CHOP), also known as growth arrest- and DNA damage-inducible gene 153 (GADD153). Here, we summarize the current understanding of the roles of CHOP/GADD153 in ER stress-mediated apoptosis and in diseases including diabetes, brain ischemia and neurodegenerative disease.

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Journal ArticleDOI

Endoplasmic reticulum stress: cell life and death decisions

TL;DR: Important roles for ER-initiated cell death pathways have been recognized for several diseases, including hypoxia, ischemia/reperfusion injury, neurodegeneration, heart disease, and diabetes.
Journal ArticleDOI

Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities

TL;DR: The accumulation of unfolded proteins in the endoplasmic reticulum represents a cellular stress induced by multiple stimuli and pathological conditions, which triggers an evolutionarily conserved series of signal-transduction events, which constitutes the unfolded protein response.
Journal ArticleDOI

ER stress-induced cell death mechanisms

TL;DR: Recent advances in understanding the diversity of molecular mechanisms that govern ER stress signaling in health and disease are summarized.
Journal ArticleDOI

Autosomal dominant polycystic kidney disease

TL;DR: An increased understanding of the disorder's underlying genetic, molecular, and cellular mechanisms and a better appreciation of its progression and systemic manifestations have laid out the foundation for the development of clinical trials and potentially effective treatments.
Journal ArticleDOI

Mammalian MAPK Signal Transduction Pathways Activated by Stress and Inflammation: A 10-Year Update

TL;DR: The molecular components of the mammalian stress-regulated MAPK pathways and their regulation as described thus far are summarized and some of the in vivo functions of these pathways are reviewed.
References
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Journal ArticleDOI

Proapoptotic BAX and BAK: A Requisite Gateway to Mitochondrial Dysfunction and Death

TL;DR: In this article, the authors found that doubly deficient cells are resistant to multiple apoptotic stimuli that act through disruption of mitochondrial function: staurosporine, ultraviolet radiation, growth factor deprivation, etoposide, and the endoplasmic reticulum stress stimuli thapsigargin and tunicamycin.
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XBP1 mRNA Is Induced by ATF6 and Spliced by IRE1 in Response to ER Stress to Produce a Highly Active Transcription Factor

TL;DR: The transcription factor XBP1, a target of ATF6, is identified as a mammalian substrate of such an unconventional mRNA splicing system and it is shown that only the spliced form of X BP1 can activate the UPR efficiently.
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Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta.

TL;DR: It is shown that caspase-12 is localized to the ER and activated by ER stress, including disruption of ER calcium homeostasis and accumulation of excess proteins in ER, but not by membrane- or mitochondrial-targeted apoptotic signals, which may contribute to amyloid-β neurotoxicity.
Journal ArticleDOI

Regulated Translation Initiation Controls Stress-Induced Gene Expression in Mammalian Cells

TL;DR: Protein kinases that phosphorylate the alpha subunit of eukaryotic initiation factor 2 (eIF2alpha) are activated in stressed cells and negatively regulate protein synthesis, resulting in the induction of the downstream gene CHOP (GADD153).
Journal ArticleDOI

An Integrated Stress Response Regulates Amino Acid Metabolism and Resistance to Oxidative Stress

TL;DR: A signaling pathway initiated by eIF2alpha phosphorylation protects cells against metabolic consequences of ER oxidation by promoting the linked processes of amino acid sufficiency and resistance to oxidative stress.
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