scholarly journals Dengue Virus Modulates the Unfolded Protein Response in a Time-dependent Manner

2011 ◽  
Vol 286 (16) ◽  
pp. 14226-14236 ◽  
Author(s):  
José Peña ◽  
Eva Harris
Keyword(s):  
Dengue Virus ◽  
Unfolded Protein Response ◽  
Time Dependent ◽  
Dependent Manner ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals Protein Serine/Threonine Phosphatase Ptc2p Negatively Regulates the Unfolded-Protein Response by Dephosphorylating Ire1p Kinase

1998 ◽  
Vol 18 (4) ◽  
pp. 1967-1977 ◽  
Author(s):  
Ajith A. Welihinda ◽  
Witoon Tirasophon ◽  
Sarah R. Green ◽  
Randal J. Kaufman
Keyword(s):  
Unfolded Protein Response ◽  
Transmembrane Protein ◽  
Null Alleles ◽  
Dependent Manner ◽  
Unfolded Proteins ◽  
Interaction Domain ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Upr Pathway

ABSTRACT Cells respond to the accumulation of unfolded proteins in the endoplasmic reticulum (ER) by increasing the transcription of the genes encoding ER-resident chaperone proteins. Ire1p is a transmembrane protein kinase that transmits the signal from unfolded proteins in the lumen of the ER by a mechanism that requires oligomerization andtrans-autophosphorylation of its cytoplasmic-nucleoplasmic kinase domain. Activation of Ire1p induces a novel spliced form ofHAC1 mRNA that produces Hac1p, a transcription factor that is required for activation of the transcription of genes under the control of the unfolded-protein response (UPR) element. Searching for proteins that interact with Ire1p in Saccharomyces cerevisiae, we isolated PTC2, which encodes a serine/threonine phosphatase of type 2C. The Ptc2p interaction with Ire1p is specific, direct, dependent on Ire1p phosphorylation, and mediated through a kinase interaction domain within Ptc2p. Ptc2p dephosphorylates Ire1p efficiently in an Mg2+-dependent manner in vitro. PTC2 is nonessential for growth and negatively regulates the UPR pathway. Strains carrying null alleles ofPTC2 have a three- to fourfold-increased UPR and increased levels of spliced HAC1 mRNA. Overexpression of wild-type Ptc2p but not catalytically inactive Ptc2p reduces levels of splicedHAC1 mRNA and attenuates the UPR, demonstrating that the phosphatase activity of Ptc2p is required for regulation of the UPR. These results demonstrate that Ptc2p downregulates the UPR by dephosphorylating Ire1p and reveal a novel mechanism of regulation in the UPR pathway upstream of the HAC1 mRNA splicing event.

scholarly journals The role of the unfolded protein response in dengue virus pathogenesis

2017 ◽  
Vol 19 (5) ◽  
pp. e12734 ◽  
Author(s):  
Nilanka Perera ◽  
Joanna L. Miller ◽  
Nicole Zitzmann
Keyword(s):  
Dengue Virus ◽  
Unfolded Protein Response ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals SARS-CoV-2 ORF3a Induces Incomplete Autophagy via the Unfolded Protein Response

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2467
Author(s):  
Wenqing Su ◽  
Xuejie Yu ◽  
Chuanmin Zhou
Keyword(s):  
Unfolded Protein Response ◽  
Viral Infections ◽  
Dependent Manner ◽  
Therapeutic Modalities ◽  
Unfolded Protein ◽  
The Past ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Upr Pathway

In the past year and a half, SARS-CoV-2 has caused 240 million confirmed cases and 5 million deaths worldwide. Autophagy is a conserved process that either promotes or inhibits viral infections. Although coronaviruses are known to utilize the transport of autophagy-dependent vesicles for the viral life cycle, the underlying autophagy-inducing mechanisms remain largely unexplored. Using several autophagy-deficient cell lines and autophagy inhibitors, we demonstrated that SARS-CoV-2 ORF3a was able to induce incomplete autophagy in a FIP200/Beclin-1-dependent manner. Moreover, ORF3a was involved in the induction of the UPR (unfolded protein response), while the IRE1 and ATF6 pathways, but not the PERK pathway, were responsible for mediating the ORF3a-induced autophagy. These results identify the role of the UPR pathway in the ORF3a-induced classical autophagy process, which may provide us with a better understanding of SARS-CoV-2 and suggest new therapeutic modalities in the treatment of COVID-19.

Cellular Mechanisms of Endoplasmic Reticulum Stress Signaling in Health and Disease. 3. Orchestrating the unfolded protein response in oncogenesis: an update

2014 ◽  
Vol 307 (10) ◽  
pp. C901-C907 ◽  
Author(s):  
Serge N. Manié ◽  
Justine Lebeau ◽  
Eric Chevet
Keyword(s):  
Endoplasmic Reticulum ◽  
Unfolded Protein Response ◽  
Dependent Manner ◽  
Cellular Mechanisms ◽  
Unfolded Protein ◽  
Stress Sensors ◽  
Plasma Membrane Receptor ◽  
The Unfolded Protein Response ◽  
Stress Dependent ◽  
Protein Response

The endoplasmic reticulum (ER)-induced unfolded protein response (UPR) is an adaptive mechanism that is activated upon accumulation of misfolded proteins in the ER and aims at restoring ER homeostasis. In the past 10 years, the UPR has emerged as an important actor in the different phases of tumor growth. The UPR is transduced by three major ER resident stress sensors, which are protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme-1 (IRE1). The signaling pathways elicited by those stress sensors have connections with metabolic pathways and with other plasma membrane receptor signaling networks. As such, the ER has an essential position as a signal integrator in the cell and is instrumental in the different phases of tumor progression. Herein, we describe and discuss the characteristics of an integrated signaling network that might condition the UPR biological outputs in a tissue- or stress-dependent manner. We discuss these issues in the context of the pathophysiological roles of UPR signaling in cancers.

scholarly journals Dengue virus serotype infection specifies the activation of the unfolded protein response

2007 ◽  
Vol 4 (1) ◽  
pp. 91 ◽  
Author(s):  
Indira Umareddy ◽  
Olivier Pluquet ◽  
Qing Wang ◽  
Subhash G Vasudevan ◽  
Eric Chevet ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Unfolded Protein Response ◽  
Unfolded Protein ◽  
Virus Serotype ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals The unfolded protein response in Pichia pastoris without external stressing stimuli

2020 ◽  
Vol 20 (7) ◽  
Author(s):  
Yasmin Nabilah Binti Mohd Fauzee ◽  
Naoki Taniguchi ◽  
Yuki Ishiwata-Kimata ◽  
Hiroshi Takagi ◽  
Yukio Kimata
Keyword(s):  
Pichia Pastoris ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Gene Knockout ◽  
Transmembrane Protein ◽  
Dependent Manner ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Stress Dependent ◽  
Protein Response

ABSTRACT Dysfunction or capacity shortage of the endoplasmic reticulum (ER) is cumulatively called ER stress and provokes the unfolded protein response (UPR). In various yeast species, the ER-located transmembrane protein Ire1 is activated upon ER stress and performs the splicing reaction of HAC1 mRNA, the mature form of which is translated into a transcription factor protein that is responsible for the transcriptome change on the UPR. Here we carefully assessed the splicing of HAC1 mRNA in Pichia pastoris (Komagataella phaffii) cells. We found that, inconsistent with previous reports by others, the HAC1 mRNA was substantially, but partially, spliced even without ER-stressing stimuli. Unlike Saccharomyces cerevisiae, growth of P. pastoris was significantly retarded by the IRE1-gene knockout mutation. Moreover, P. pastoris cells seemed to push more abundant proteins into the secretory pathway than S. cerevisiae cells. We also suggest that P. pastoris Ire1 has the ability to control its activity stringently in an ER stress-dependent manner. We thus propose that P. pastoris cells are highly ER-stressed possibly because of the high load of endogenous proteins into the ER.

scholarly journals Ceapins block the unfolded protein response sensor ATF6α by inducing a neomorphic inter-organelle tether

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Sandra Elizabeth Torres ◽  
Ciara M Gallagher ◽  
Lars Plate ◽  
Meghna Gupta ◽  
Christina R Liem ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Unfolded Protein Response ◽  
Dependent Manner ◽  
Unknown Mechanism ◽  
Unfolded Protein ◽  
Genome Wide ◽  
Transmembrane Regions ◽  
The Unfolded Protein Response ◽  
Protein Response

The unfolded protein response (UPR) detects and restores deficits in the endoplasmic reticulum (ER) protein folding capacity. Ceapins specifically inhibit the UPR sensor ATF6α, an ER-tethered transcription factor, by retaining it at the ER through an unknown mechanism. Our genome-wide CRISPR interference (CRISPRi) screen reveals that Ceapins function is completely dependent on the ABCD3 peroxisomal transporter. Proteomics studies establish that ABCD3 physically associates with ER-resident ATF6α in cells and in vitro in a Ceapin-dependent manner. Ceapins induce the neomorphic association of ER and peroxisomes by directly tethering the cytosolic domain of ATF6α to ABCD3’s transmembrane regions without inhibiting or depending on ABCD3 transporter activity. Thus, our studies reveal that Ceapins function by chemical-induced misdirection which explains their remarkable specificity and opens up new mechanistic routes for drug development and synthetic biology.

Oestrogen-driven changes in the bovine uterus are associated with activation of the unfolded protein response

2014 ◽  
Author(s):  
Mohammed A Alfattah ◽  
Paul Anthony McGettigan ◽  
John Arthur Browne ◽  
Khalid M Alkhodair ◽  
Katarzyna Pluta ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response
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