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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p58(IPK)-mediated attenuation of the proapoptotic PERK-CHOP pathway allows malignant progression upon low glucose.
Anne-Laure Huber,Justine Lebeau,Justine Lebeau,Patricia Guillaumot,Patricia Guillaumot,Virginie Pétrilli,Virginie Pétrilli,Mouhannad Malek,Mouhannad Malek,Julien Chilloux,Frédérique Fauvet,Frédérique Fauvet,Léa Payen,Alain Kfoury,Alain Kfoury,Toufic Renno,Toufic Renno,Eric Chevet,Serge Manié,Serge Manié +19 more
TL;DR: In this paper, a mouse model of K-ras(G12V)-induced lung cancer was used to investigate the role of endoplasmic reticulum (ER) unfolded protein response (UPR) activation and p58(IPK) expression.
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Luman/CREB3 Induces Transcription of the Endoplasmic Reticulum (ER) Stress Response Protein Herp through an ER Stress Response Element
Genqing Liang,Timothy E. Audas,Yu Li,Gregory P. Cockram,J. Doug Dean,Amanda C. Martyn,Koichi Kokame,Rui Lu +7 more
TL;DR: It is proposed that Luman is a novel factor that plays a role in ERAD and a converging point for various signaling pathways channeling through the ER.
Journal ArticleDOI
Brain-Specific Disruption of the eIF2α Kinase PERK Decreases ATF4 Expression and Impairs Behavioral Flexibility
TL;DR: The findings reveal that PERK plays a critical role in information processing and cognitive function and that modulation of eIF2α phosphorylation and ATF4 expression may represent an effective strategy for treating behavioral inflexibility associated with several neurological disorders such as schizophrenia.
Journal ArticleDOI
Crosstalk between ER stress and immunogenic cell death.
Oliver Kepp,Laurie Menger,Laurie Menger,Laurie Menger,Erika Vacchelli,Erika Vacchelli,Erika Vacchelli,Clara Locher,Clara Locher,Sandy Adjemian,Sandy Adjemian,Sandy Adjemian,Takahiro Yamazaki,Takahiro Yamazaki,Isabelle Martins,Isabelle Martins,Isabelle Martins,Abdul Qader Sukkurwala,Abdul Qader Sukkurwala,Abdul Qader Sukkurwala,Michael Michaud,Michael Michaud,Michael Michaud,Laura Senovilla,Laura Senovilla,Laura Senovilla,Lorenzo Galluzzi,Lorenzo Galluzzi,Guido Kroemer,Laurence Zitvogel +29 more
TL;DR: Recent findings in the field of ICD research are summarized with a special focus on ER stress mechanisms and their implication for cancer therapy.
Journal ArticleDOI
Emerging roles of ER stress and unfolded protein response pathways in skeletal muscle health and disease
TL;DR: The role and potential mechanisms by which ER stress and the individual arms of the UPR regulate skeletal muscle formation, plasticity, and function in various physiological and pathophysiological conditions are discussed.
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.