Mechanisms, regulation and functions of the unfolded protein response

Nature Reviews Molecular Cell Biology, Год журнала: 2020, Номер 21(8), С. 421 - 438

Опубликована: Май 26, 2020

Язык: Английский

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Endoplasmic reticulum stress and unfolded protein response in cardiovascular diseases

Nature Reviews Cardiology, Год журнала: 2021, Номер 18(7), С. 499 - 521

Опубликована: Фев. 22, 2021

Язык: Английский

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Structure and Molecular Mechanism of ER Stress Signaling by the Unfolded Protein Response Signal Activator IRE1

Frontiers in Molecular Biosciences, Год журнала: 2019, Номер 6

Опубликована: Март 12, 2019

The endoplasmic reticulum (ER) is an important site for protein folding and maturation in eukaryotes. cellular requirement to synthesize proteins within the ER matched by its capacity. However, physiological demands or aberrations may result imbalance which can lead accumulation of misfolded protein, also known as "ER stress." unfolded response (UPR) a cell-signaling system that readjusts capacity restore homeostasis. key UPR signal activator, IRE1, responds stress propagating from cytosol. Here, we discuss structural molecular basis IRE1 signaling, with particular focus on novel mechanistic advances. We draw comparison between recently proposed allosteric model induction role Hsp70 during polypeptide import mitochondrial matrix.

Язык: Английский

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Protein quality control in the secretory pathway

The Journal of Cell Biology, Год журнала: 2019, Номер 218(10), С. 3171 - 3187

Опубликована: Сен. 19, 2019

Protein folding is inherently error prone, especially in the endoplasmic reticulum (ER). Even with an elaborate network of molecular chaperones and protein facilitators, misfolding can occur quite frequently. To maintain homeostasis, eukaryotes have evolved a series quality-control checkpoints. When secretory pathway pathways fail, stress response pathways, such as unfolded (UPR), are induced. In addition, ER, which initial hub biogenesis pathway, triages misfolded proteins by delivering substrates to proteasome or lysosome/vacuole through ER-associated degradation (ERAD) ER-phagy. Some escape ER instead selected for Golgi quality control. These targeted after retrieval delivery lysosome/vacuole. Here, we discuss how these guardian function, their activities intersect upon induction UPR, decisions made dispose pathway.

Язык: Английский

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UPR proteins IRE1 and PERK switch BiP from chaperone to ER stress sensor

Nature Structural & Molecular Biology, Год журнала: 2019, Номер 26(11), С. 1053 - 1062

Опубликована: Ноя. 1, 2019

Язык: Английский

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Pharmacological targeting of the unfolded protein response for disease intervention

Nature Chemical Biology, Год журнала: 2019, Номер 15(8), С. 764 - 775

Опубликована: Июль 18, 2019

Язык: Английский

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Functional Modules of the Proteostasis Network

Cold Spring Harbor Perspectives in Biology, Год журнала: 2019, Номер 12(1), С. a033951 - a033951

Опубликована: Март 4, 2019

Gopal G. Jayaraj, Mark S. Hipp and F. Ulrich Hartl Department of Cellular Biochemistry, Max Planck Institute Am Klopferspitz 18, 82152 Martinsried, Germany Correspondence: uhartl{at}biochem.mpg.de

Язык: Английский

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A cross-kingdom conserved ER-phagy receptor maintains endoplasmic reticulum homeostasis during stress

eLife, Год журнала: 2020, Номер 9

Опубликована: Авг. 27, 2020

Eukaryotes have evolved various quality control mechanisms to promote proteostasis in the endoplasmic reticulum (ER). Selective removal of certain ER domains via autophagy (termed as ER-phagy) has emerged a major mechanism. However, degree which ER-phagy is employed by other branches ER-quality remains largely elusive. Here, we identify cytosolic protein, C53, that specifically recruited autophagosomes during ER-stress, both plant and mammalian cells. C53 interacts with ATG8 distinct binding epitope, featuring shuffled interacting motif (sAIM). senses proteotoxic stress lumen forming tripartite receptor complex ER-associated ufmylation ligase UFL1 its membrane adaptor DDRGK1. The C53/UFL1/DDRGK1 activated stalled ribosomes induces degradation internal or passenger proteins ER. Consistently, mutants are highly susceptible stress. Thus, forms an ancient pathway bridges selective ribosome-associated

Язык: Английский

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The aftermath of the interplay between the endoplasmic reticulum stress response and redox signaling

Experimental & Molecular Medicine, Год журнала: 2021, Номер 53(2), С. 151 - 167

Опубликована: Фев. 1, 2021

Abstract The endoplasmic reticulum (ER) is an essential organelle of eukaryotic cells. Its main functions include protein synthesis, proper folding, modification, and the transportation synthesized proteins. Any perturbations in ER function, such as increased demand for folding or accumulation unfolded misfolded proteins lumen, lead to a stress response called (UPR). primary aim UPR restore cellular homeostasis; however, it triggers apoptotic signaling during prolonged stress. core mechanisms response, failure respond stress, final fate cell are not yet clear. Here, we discuss cross talk between mitochondria its significance, conditions that can trigger failure. We also describe how redox environment affects vice versa, aftermath integrating discussion on imbalance-induced progressing death dynamic pathophysiological changes.

Язык: Английский

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Early Events in the Endoplasmic Reticulum Unfolded Protein Response

Cold Spring Harbor Perspectives in Biology, Год журнала: 2018, Номер 11(4), С. a033894 - a033894

Опубликована: Ноя. 5, 2018

Steffen Preissler and David Ron Cambridge Institute for Medical Research, University of Cambridge, CB2 0XY, United Kingdom Correspondence: sp693{at}cam.ac.uk; dr360{at}medschl.cam.ac.uk

Язык: Английский

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