Journal ArticleDOI
Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase
Reads0
Chats0
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
Citations
More filters
Journal ArticleDOI
Yeast unfolded protein response pathway regulates expression of genes for anti-oxidative stress and for cell surface proteins.
TL;DR: This analysis revealed that in addition to the previously known UPR targets, some anti‐oxidative stress genes were up‐regulated by the Ire1‐HAC1 pathway, possibly in order to reduce reactive oxygen species produced during the cellular response to ER stress.
Journal ArticleDOI
AtWRKY15 perturbation abolishes the mitochondrial stress response that steers osmotic stress tolerance in Arabidopsis
Sandy Vanderauwera,Korneel Vandenbroucke,Annelies Inzé,Brigitte van de Cotte,Per Mühlenbock,Riet De Rycke,Naïra Naouar,Tim Van Gaever,Marc Van Montagu,Frank Van Breusegem +9 more
TL;DR: It is demonstrated that the ROS-inducible Arabidopsis thaliana WRKY15 transcription factor (AtWRKY15) modulates plant growth and salt/osmotic stress responses and might be important for regulating an active mitochondrial retrograde signaling and launching an appropriate defense response to confer salt-stress tolerance.
Journal ArticleDOI
Upregulation of BiP and CHOP by the unfolded-protein response is independent of presenilin expression.
Naoyuki Sato,Fumihiko Urano,Yoon Leem J,Seong-Hun Kim,Li M,Dorit B. Donoviel,Alan Bernstein,Lee As,David Ron,Margaret Veselits,Sangram S. Sisodia,Gopal Thinakaran +11 more
TL;DR: It is shown that that neither the endoplasmic reticulum (ER) stress-induced accumulation of BiP and CHOP messenger RNA, nor the activation of ER stress kinases IRE1α and PERK, is compromised in cells lacking both PS1 and PS2 or in cells expressing FAD-linked PS1 variants.
Journal ArticleDOI
Signaling pathways from the endoplasmic reticulum and their roles in disease.
Hisae Kadowaki,Hideki Nishitoh +1 more
TL;DR: This review will discuss the molecular mechanisms of the UPR and ER stress-induced apoptosis, as well as the possible roles of ER stress in several diseases.
Journal ArticleDOI
Dysfunction of the unfolded protein response during global brain ischemia and reperfusion.
TL;DR: Data indicate that there is dysfunction in several key components of the UPR that abrogate the effects of ER stress, which may play a significant role in reperfusion neuronal death in other systems.
References
More filters
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.