Journal ArticleDOI
Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase
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TLDR
The cloning of perk is described, a gene encoding a type I transmembrane ER-resident protein that contains a protein-kinase domain most similar to that of the known eIF2α kinases, PKR and HRI that implicate PERK in a signalling pathway that attenuates protein translation in response to ER stress.Abstract:
Protein synthesis and the folding of the newly synthesized proteins into the correct three-dimensional structure are coupled in cellular compartments of the exocytosis pathway by a process that modulates the phosphorylation level of eukaryotic initiation factor-2alpha (eIF2alpha) in response to a stress signal from the endoplasmic reticulum (ER). Activation of this process leads to reduced rates of initiation of protein translation during ER stress. Here we describe the cloning of perk, a gene encoding a type I transmembrane ER-resident protein. PERK has a lumenal domain that is similar to the ER-stress-sensing lumenal domain of the ER-resident kinase Ire1, and a cytoplasmic portion that contains a protein-kinase domain most similar to that of the known eIF2alpha kinases, PKR and HRI. ER stress increases PERK's protein-kinase activity and PERK phosphorylates eIF2alpha on serine residue 51, inhibiting translation of messenger RNA into protein. These properties implicate PERK in a signalling pathway that attenuates protein translation in response to ER stress.read more
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Journal ArticleDOI
Mfn2 modulates the UPR and mitochondrial function via repression of PERK.
Juan Pablo Muñoz,Saška Ivanova,Saška Ivanova,Jana Sánchez-Wandelmer,Jana Sánchez-Wandelmer,Paula Martínez-Cristóbal,Paula Martínez-Cristóbal,Eduard Noguera,Eduard Noguera,Ana Sancho,Ana Sancho,Angels Díaz-Ramos,Angels Díaz-Ramos,María Isabel Hernández-Alvarez,María Isabel Hernández-Alvarez,David Sebastián,David Sebastián,Caroline Mauvezin,Caroline Mauvezin,Manuel Palacín,Antonio Zorzano,Antonio Zorzano +21 more
TL;DR: The data indicate that Mfn2 is an upstream modulator of PERK, and Mfn1 loss‐of‐function reveals that PERK is a key regulator of mitochondrial morphology and function.
Journal ArticleDOI
Translational Control of Viral Gene Expression in Eukaryotes
TL;DR: The varied and complex translational programs employed by eukaryotic viruses are reviewed to discuss how these translational strategies have been incorporated into the virus life cycle and examine how such programming contributes to the pathogenesis of the host cell.
Journal ArticleDOI
Protein folding and conformational stress in microbial cells producing recombinant proteins: a host comparative overview
Brigitte Gasser,Markku Saloheimo,Ursula Rinas,Martin Dragosits,Escarlata Rodríguez-Carmona,Kristin Baumann,Maria Giuliani,Ermenegilda Parrilli,Paola Branduardi,Christine Lang,Danilo Porro,Pau Ferrer,Maria Luisa Tutino,Diethard Mattanovich,Antonio Villaverde +14 more
TL;DR: In this article, the main cellular players of this complex process are described for the most important cell factories used for biotechnological purposes, and the characterization of such adverse conditions and the elicited cell responses have permitted to better understand the physiology and molecular biology of conformational stress.
Journal ArticleDOI
Japanese encephalitis virus infection initiates endoplasmic reticulum stress and an unfolded protein response.
TL;DR: It is demonstrated that as evidenced by certain chaperone inductions, Jev infection triggers the UPR in fibroblast BHK-21 cells and in neuronal N18 and NT-2 cells, in which JEV results in apoptotic cell death, suggesting that virus-induced ER stress may participate, via p38-dependent and CHOP-mediated pathways, in the apoptotic process triggered by JEV infection.
Journal ArticleDOI
ER Stress and Its Functional Link to Mitochondria: Role in Cell Survival and Death
TL;DR: The signaling/communication between the ER and mitochondria is discussed and the role of the mitochondrial permeability transition pore in these complex processes is focused on, which provides an adaptive mechanism by which cells can augment protein folding and processing capacities of the ER.
References
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Journal ArticleDOI
Oligomerization and phosphorylation of the Ire1p kinase during intracellular signaling from the endoplasmic reticulum to the nucleus.
Caroline E. Shamu,Peter Walter +1 more
TL;DR: Molecular genetic and biochemical studies described here suggest that, as in the case of growth factor receptors of higher eukaryotic cells, Ire1p oligomerizes in response to the accumulation of unfolded proteins in the ER and is phosphorylated in trans by otherIre1p molecules as a result of oligomerization.
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Protein folding in the cell.
TL;DR: Folding and assembly of polypeptides in vivo involves other proteins, many of which belong to families that have been highly conserved during evolution.
Journal ArticleDOI
The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins
TL;DR: Testing the hypothesis that the presence of malfolded proteins may be the primary signal for induction of GRPs by expressing wild-type and mutant forms of influenza virus haemagglutinin in simian cells shows that malfoldingper se, rather than abnormal glycosylation1, is the proximal inducer of this family of stress proteins.
Journal ArticleDOI
Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase
TL;DR: IRE1 encodes a transmembrane serine/threonine kinase that it is proposed transmits the unfolded protein signal across the ER or inner nuclear membrane, suggesting that the induction of ER resident proteins is coupled to the biogenesis of new ER membrane.
Journal ArticleDOI
A stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells
TL;DR: HIre1p is an essential proximal sensor of the unfolded protein response pathway in mammalian cells and is demonstrated to be highly conserved to the yeast counterpart having a Ser/Thr protein kinase domain and a domain homologous to RNase L.