The mammalian unfolded protein response.

By M. Schröder, R. Kaufman. Annual Review of Biochemistry, 2003

3,122 citations recorded by the source corpus.

In the endoplasmic reticulum (ER), secretory and transmembrane proteins fold into their native conformation and undergo posttranslational modifications important for their activity and structure. When protein folding in the ER is inhibited, signal transduction pathways, which increase the biosynthetic capacity and decrease the biosynthetic burden of the ER to maintain the homeostasis of this organelle, are activated. These pathways are called the unfolded protein response (UPR). In this review, we briefly summarize principles of protein folding and molecular chaperone function important for a mechanistic understanding of UPR-signaling events. We then discuss mechanisms of signal transduction employed by the UPR in mammals and our current understanding of the remodeling of cellular processes by the UPR. Finally, we summarize data that demonstrate that UPR signaling feeds into decision making in other processes previously thought to be unrelated to ER function, e.g., eukaryotic starvation responses and differentiation programs.

Subfields: Cell Biology, Epidemiology, Surgery

View Paper: https://www.semanticscholar.org/paper/8ec55e43ab7578f7690931c6351f39be3cf514af

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Citations in the corpus

Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease (2015, positive): “In the case of Nrf2−/− mice, it has been concluded that the UPR is at least partially triggered under basal conditions on the basis that Chop and Xbp1s are elevated and the phosphorylation of eIF2α is increased in livers of mutant mice fed a normal chow diet [162].”
Mediators of endoplasmic reticulum stress‐induced apoptosis (2006, background): “However, this attenuation of translation is not absolute; genes carrying certain regulatory sequences in their 5 untranslated regions—for example, the internal ribosomal entry site (IRES)— can bypass the eIF2 -dependent translational block (Schroder & Kaufman, 2005).”
Endoplasmic Reticulum Stress and Associated ROS (2016, background): “The ER is the primary organelle for secretory pathways in all eukaryotic cells [1,2].”
AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan (2011, background): “The endoplasmic reticulum (ER) is a sensitive nutrient sensor, e.g., unfolded protein response (UPR) becomes activated in response to hyperglycemia and fatty acid overload [12].”
Endoplasmic Reticulum Stress and Oxidative Stress: A Vicious Cycle or a Double-Edged Sword? (2007, neutral): “Coordinate regulation of all these processes is required to restore proper protein folding and ER homeostasis (40, 63, 86, 107, 122, 150).”
Hsp90 cochaperone Aha1 downregulation rescues misfolding of CFTR in cystic fibrosis. (2006, background): “Under these conditions, we have not detected a change in the total pools of Hsc-Hsp70 or BiP, indicating that it is unlikely that we induce a general stress response (Schroder and Kaufman, 2005) by siRNA reduction of Aha1.”
From acute ER stress to physiological roles of the Unfolded Protein Response (2006, background): “knowledge of the molecular logic of UPR signaling pathways, which has been thoroughly reviewed.(4) However, as analysis of increasing numbers of murine genetic models created with”
From endoplasmic-reticulum stress to the inflammatory response (2008, background): “To ensure the fidelity of protein folding and to prevent such an accumulation of unfolded or misfolded proteins, eukaryotic cells have evolved the UPR, which alters a cell's transcriptional and translational programs to cope with stressful conditions and to resolve the protein-folding defec”
TopologyNet: Topology based deep convolutional and multi-task neural networks for biomolecular property predictions (2017, background): “Aside from some unusual exceptions, 112,113 proteins fold in particular three-dimensional structures to provide the structural basis for living organisms.”
The impact of the unfolded protein response on human disease (2012, background): “The ER is a highly dynamic organelle and responds to environmental stress and developmental cues through a series of signaling cascades known as the unfolded protein response (UPR; Schröder and Kaufman, 2005).”
The unfolded protein response: controlling cell fate decisions under ER stress and beyond (2012, background): “The UPR transduces information about the protein-folding status in the ER lumen to the nucleus and cytosol to buffer fluctuations in unfolded protein loa”
Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes (2007, background): “When ER function is severely impaired, apoptosis is induced by enhanced transcription of DNA-damage inducible transcript 3 (DDIT3, previously known as C/EBP homologous protein [CHOP]) [11, 12] and by activation of mitogen-activated protein kinase 8 (MAPK8, formerly known as JNK1) and caspase-12 [7–9”