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
The STT3a Subunit Isoform of the Arabidopsis Oligosaccharyltransferase Controls Adaptive Responses to Salt/Osmotic Stress
Hisashi Koiwa,Fang Li,Michael G. McCully,Imelda Mendoza,Nozomu Koizumi,Yuzuki Manabe,Yuko Nakagawa,Jianhua Zhu,Ana Rus,José M. Pardo,Ray A. Bressan,Paul M. Hasegawa +11 more
TL;DR: The results indicate that plant salt stress adaptation involves ER stress signal regulation of cell cycle progression, and that the pivotal and specific protein glycosylation that is a necessary for recovery from the unfolded protein response and forcell cycle progression during salt/osmotic stress recovery is associated uniquely with the function of the STT3a isoform.
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Translational Control of Cytochrome c by RNA-Binding Proteins TIA-1 and HuR
Tomoko Kawai,Ashish Lal,Xiaoling Yang,Stefanie Galbán,Krystyna Mazan-Mamczarz,Myriam Gorospe +5 more
TL;DR: It is proposed that HuR and TIA-1 function coordinately to maintain precise levels of cy tochrome c production under unstimulated conditions and to modify cytochrome c translation when damaged cells are faced with molecular decisions to follow a prosurvival or a prodeath path.
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Sleep deprivation induces the unfolded protein response in mouse cerebral cortex.
TL;DR: Ending wakefulness beyond a certain duration induces the UPR indicating a physiological limit to wakefulness, as shown in mice maintained on a 12:12 light/dark cycle.
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Antiviral effect of the mammalian translation initiation factor 2α kinase GCN2 against RNA viruses
Juan José Berlanga,Iván Ventoso,Heather P. Harding,Jing Deng,Jing Deng,David Ron,Nahum Sonenberg,Luis Carrasco,César de Haro +8 more
TL;DR: It is determined that GCN2 inhibits SV replication by blocking early viral translation of genomic SV RNA and point to a hitherto unrecognized role ofGCN2 as an early mediator in the cellular response to RNA viruses.
Journal ArticleDOI
Glucose Limitation Induces GCN4 Translation by Activation of Gcn2 Protein Kinase
TL;DR: There are differences between the mechanisms regulating Gcn2p activity in response to amino acid and carbohydrate deficiency, suggesting a linkage between amino acid control and glycogen metabolism.
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.
Journal ArticleDOI
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.