Mediators of endoplasmic reticulum stress-induced apoptosis.
TLDR
The role of the molecules that are activated during the UPR is examined in order to identify the molecular switch from the adaptive phase to apoptosis and how the activation of these molecules leads to the commitment of death and the mechanisms that are responsible for the final demise of the cell.Abstract:
The efficient functioning of the endoplasmic reticulum (ER) is essential for most cellular activities and survival. Conditions that interfere with ER function lead to the accumulation and aggregation of unfolded proteins. ER transmembrane receptors detect the onset of ER stress and initiate the unfolded protein response (UPR) to restore normal ER function. If the stress is prolonged, or the adaptive response fails, apoptotic cell death ensues. Many studies have focused on how this failure initiates apoptosis, as ER stress-induced apoptosis is implicated in the pathophysiology of several neurodegenerative and cardiovascular diseases. In this review, we examine the role of the molecules that are activated during the UPR in order to identify the molecular switch from the adaptive phase to apoptosis. We discuss how the activation of these molecules leads to the commitment of death and the mechanisms that are responsible for the final demise of the cell.read more
Citations
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Journal ArticleDOI
Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress.
Ira Tabas,David Ron +1 more
TL;DR: The molecular mechanisms linking ER stress to apoptosis are the topic of this review, with emphases on relevance to pathophysiology and integration and complementation among the various apoptotic pathways induced by ER stress.
Journal ArticleDOI
The integrated stress response.
Karolina Pakos-Zebrucka,Izabela Koryga,Katarzyna Mnich,Mila Ljujic,Afshin Samali,Adrienne M. Gorman +5 more
TL;DR: Current understanding of the ISR signaling is reviewed and how it regulates cell fate under diverse types of stress is reviewed.
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Cellular Stress Responses: Cell Survival and Cell Death
TL;DR: The implications of cellular stress responses to human physiology and diseases are manifold and will be discussed in this review in the context of some major world health issues such as diabetes, Parkinson's disease, myocardial infarction, and cancer.
Journal ArticleDOI
Role of ROS and RNS Sources in Physiological and Pathological Conditions
TL;DR: The most recent data, besides confirming the mitochondrial role in tissue oxidative stress and protection, show interplay between mitochondria and other ROS cellular sources, so that activation of one can lead to activation of other sources.
Journal ArticleDOI
The impact of the endoplasmic reticulum protein-folding environment on cancer development.
Miao Wang,Randal J. Kaufman +1 more
TL;DR: The impact of ER stress and UPR activation on every aspect of cancer is summarized and outstanding questions for which answers will pave the way for therapeutics are discussed.
References
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Journal ArticleDOI
Signal transduction by the JNK group of MAP kinases.
TL;DR: This review will focus on the JNK group of MAP kinases, which are characterized by the sequence TEY and the two stress-activatedMAP kinases: p38 with the sequence TGY, and the c-Jun NH2-terminal kinases (JNK) with the sequences TPY.
Journal ArticleDOI
Proapoptotic BAX and BAK: A Requisite Gateway to Mitochondrial Dysfunction and Death
Michael C. Wei,Michael C. Wei,Wei-Xing Zong,Emily H. Cheng,Tullia Lindsten,Vily Panoutsakopoulou,Andrea J. Ross,Kevin A. Roth,Grant R. MacGregor,Craig B. Thompson,Stanley J. Korsmeyer +10 more
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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
An Integrated Stress Response Regulates Amino Acid Metabolism and Resistance to Oxidative Stress
Heather P. Harding,Yuhong Zhang,Huiquing Zeng,Isabel Novoa,Phoebe D. Lu,Marcella Calfon,Navid Sadri,Chi Yun,Brian Popko,Richard S. Paules,David F. Stojdl,John C. Bell,Thore Hettmann,Jeffrey M. Leiden,David Ron +14 more
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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