scholarly journals Differences in the Molecular Mechanisms Involved in the Transcriptional Activation of theCHOPand Asparagine Synthetase Genes in Response to Amino Acid Deprivation or Activation of the Unfolded Protein Response

2002 ◽  
Vol 277 (50) ◽  
pp. 48107-48114 ◽  
Author(s):  
Alain Bruhat ◽  
Julien Averous ◽  
Valérie Carraro ◽  
Can Zhong ◽  
Andreas M. Reimold ◽  
...  
Keyword(s):  
Amino Acid ◽  
Unfolded Protein Response ◽  
Transcriptional Activation ◽  
Molecular Mechanisms ◽  
Asparagine Synthetase ◽  
Amino Acid Deprivation ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals Activation of the Unfolded Protein Response Pathway Induces Human Asparagine Synthetase Gene Expression

1999 ◽  
Vol 274 (44) ◽  
pp. 31139-31144 ◽  
Author(s):  
Ione P. Barbosa-Tessmann ◽  
Chin Chen ◽  
Can Zhong ◽  
Sheldon M. Schuster ◽  
Harry S. Nick ◽  
...  
Keyword(s):  
Gene Expression ◽  
Unfolded Protein Response ◽  
Asparagine Synthetase ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

Intestinal Amino Acid Availability via PEPT-1 Affects TORC1/2 Signaling and the Unfolded Protein Response

2014 ◽  
Vol 13 (8) ◽  
pp. 3685-3692 ◽  
Author(s):  
Kerstin E. Geillinger ◽  
Katja Kuhlmann ◽  
Martin Eisenacher ◽  
Pieter Giesbertz ◽  
Helmut E. Meyer ◽  
...  
Keyword(s):  
Amino Acid ◽  
Unfolded Protein Response ◽  
Unfolded Protein ◽  
Amino Acid Availability ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals Amino acid limitation regulates CHOP expression through a specific pathway independent of the unfolded protein response

FEBS Letters ◽  
1999 ◽  
Vol 448 (2-3) ◽  
pp. 211-216 ◽  
Author(s):  
Céline Jousse ◽  
Alain Bruhat ◽  
Heather P Harding ◽  
Marc Ferrara ◽  
David Ron ◽  
...  
Keyword(s):  
Amino Acid ◽  
Unfolded Protein Response ◽  
Unfolded Protein ◽  
Chop Expression ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Specific Pathway

scholarly journals Modulation of the Unfolded Protein Response by the Severe Acute Respiratory Syndrome Coronavirus Spike Protein

2006 ◽  
Vol 80 (18) ◽  
pp. 9279-9287 ◽  
Author(s):  
Ching-Ping Chan ◽  
Kam-Leung Siu ◽  
King-Tung Chin ◽  
Kwok-Yung Yuen ◽  
Bojian Zheng ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Unfolded Protein Response ◽  
Signaling Pathways ◽  
Transcriptional Activation ◽  
Cultured Cells ◽  
Protein A ◽  
S Protein ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

ABSTRACT Perturbation of the function of endoplasmic reticulum (ER) causes stress leading to the activation of cell signaling pathways known as the unfolded protein response (UPR). Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) uses ER as a site for synthesis and processing of viral proteins. In this report, we demonstrate that infection with SARS-CoV induces the UPR in cultured cells. A comparison with M, E, and NSP6 proteins indicates that SARS-CoV spike (S) protein sufficiently induces transcriptional activation of several UPR effectors, including glucose-regulated protein 78 (GRP78), GRP94, and C/EBP homologous protein. A substantial amount of S protein accumulates in the ER. The expression of S protein exerts different effects on the three major signaling pathways of the UPR. Particularly, it induces GRP78/94 through PKR-like ER kinase but has no influence on activating transcription factor 6 or X box-binding protein 1. Taken together, our findings suggest that SARS-CoV S protein specifically modulates the UPR to facilitate viral replication.

scholarly journals GTPase-Mediated Regulation of the Unfolded Protein Response in Caenorhabditis elegans Is Dependent on the AAA+ ATPase CDC-48

2008 ◽  
Vol 28 (13) ◽  
pp. 4261-4274 ◽  
Author(s):  
Marie-Elaine Caruso ◽  
Sarah Jenna ◽  
Marion Bouchecareilh ◽  
David L. Baillie ◽  
Daniel Boismenu ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Unfolded Protein Response ◽  
Molecular Mechanisms ◽  
Small Gtpase ◽  
Transcription Control ◽  
Aaa Atpase ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Er Homeostasis

ABSTRACT When endoplasmic reticulum (ER) homeostasis is perturbed, an adaptive mechanism is triggered and named the unfolded protein response (UPR). Thus far, three known UPR signaling branches (IRE-1, PERK, and ATF-6) mediate the reestablishment of ER functions but can also lead to apoptosis if ER stress is not alleviated. However, the understanding of the molecular mechanisms integrating the UPR to other ER functions, such as membrane traffic or endomembrane signaling, remains incomplete. We consequently sought to identify new regulators of UPR-dependent transcriptional mechanisms and focused on a family of proteins known to mediate, among other, ER-related functions: the small GTP-binding proteins of the RAS superfamily. To this end, we used transgenic UPR reporter Caenorhabditis elegans strains as a model to specifically silence small-GTPase expression. We show that the Rho subfamily member CRP-1 is an essential component of UPR-induced transcriptional events through its physical and genetic interactions with the AAA+ ATPase CDC-48. In addition, we describe a novel signaling module involving CRP-1 and CDC-48 which may directly link the UPR to DNA remodeling and transcription control.

scholarly journals The Unfolded Protein Response and Autophagy on the Crossroads of Coronaviruses Infections

2021 ◽  
Vol 11 ◽  
Author(s):  
Elisa B. Prestes ◽  
Julia C. P. Bruno ◽  
Leonardo H. Travassos ◽  
Leticia A. M. Carneiro
Keyword(s):  
Viral Replication ◽  
Unfolded Protein Response ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Cellular Stress ◽  
Membrane Vesicles ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

The ability to sense and adequately respond to variable environmental conditions is central for cellular and organismal homeostasis. Eukaryotic cells are equipped with highly conserved stress-response mechanisms that support cellular function when homeostasis is compromised, promoting survival. Two such mechanisms – the unfolded protein response (UPR) and autophagy – are involved in the cellular response to perturbations in the endoplasmic reticulum, in calcium homeostasis, in cellular energy or redox status. Each of them operates through conserved signaling pathways to promote cellular adaptations that include re-programming transcription of genes and translation of new proteins and degradation of cellular components. In addition to their specific functions, it is becoming increasingly clear that these pathways intersect in many ways in different contexts of cellular stress. Viral infections are a major cause of cellular stress as many cellular functions are coopted to support viral replication. Both UPR and autophagy are induced upon infection with many different viruses with varying outcomes – in some instances controlling infection while in others supporting viral replication and infection. The role of UPR and autophagy in response to coronavirus infection has been a matter of debate in the last decade. It has been suggested that CoV exploit components of autophagy machinery and UPR to generate double-membrane vesicles where it establishes its replicative niche and to control the balance between cell death and survival during infection. Even though the molecular mechanisms are not fully elucidated, it is clear that UPR and autophagy are intimately associated during CoV infections. The current SARS-CoV-2 pandemic has brought renewed interest to this topic as several drugs known to modulate autophagy – including chloroquine, niclosamide, valinomycin, and spermine – were proposed as therapeutic options. Their efficacy is still debatable, highlighting the need to better understand the molecular interactions between CoV, UPR and autophagy.

scholarly journals Mycoplasma hyopneumoniae Inhibits Porcine Beta-Defensin 2 Production by Blocking the Unfolded Protein Response To Facilitate Epithelial Adhesion and Infection

2020 ◽  
Vol 88 (7) ◽  
Author(s):  
Qiao Pan ◽  
Xiumei Wang ◽  
Tong Liu ◽  
Ying Yu ◽  
Lu Li ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Molecular Mechanisms ◽  
Mycoplasma Hyopneumoniae ◽  
Initiation Factor ◽  
Content Type ◽  
Unfolded Protein ◽  
Eif2α Phosphorylation ◽  
Effective Interventions ◽  
The Unfolded Protein Response ◽  
Protein Response

ABSTRACT Mycoplasma hyopneumoniae causes the disease porcine enzootic pneumonia, a highly contagious and chronic disease affecting pigs. Understanding the molecular mechanisms of its pathogenicity is critical for developing effective interventions to control this swine respiratory disease. Here, we describe a novel virulence mechanism by which M. hyopneumoniae interferes with the host unfolded protein response (UPR) and eventually facilitates bacterial adhesion and infection. We observed that M. hyopneumoniae infection suppressed the UPR target molecules GRP78 and CHOP by reducing PKR-like endoplasmic reticulum kinase/eukaryotic initiation factor 2 alpha (PERK/eIF2α) phosphorylation, ATF6 cleavage, and X-box binding protein 1 (XBP1) splicing. Interestingly, further analyses revealed that host UPR inhibition subsequently suppressed the NF‐κB pathway, leading to the reduced production of porcine beta-defensin 2 (PBD-2), thus facilitating M. hyopneumoniae adherence and infection. This study provides new insights into the molecular pathogenesis of M. hyopneumoniae and sheds light upon its interactions with the host.

scholarly journals Transcriptional induction of the human asparagine synthetase gene during the unfolded protein response does not require the ATF6 and IRE1/XBP1 arms of the pathway

2009 ◽  
Vol 417 (3) ◽  
pp. 695-703 ◽  
Author(s):  
Altin Gjymishka ◽  
Nan Su ◽  
Michael S. Kilberg
Keyword(s):  
Amino Acid ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Hepg2 Cells ◽  
Binding Protein ◽  
Asparagine Synthetase ◽  
Response Element ◽  
Unfolded Protein ◽  
Protein Response ◽  
Transcriptional Induction

The UPR (unfolded protein response) pathway comprises three signalling cascades mediated by the ER (endoplasmic reticulum) stress-sensor proteins PERK [PKR (double-stranded RNA-activated protein kinase)-like ER kinase], IRE1 (inositol-requiring kinase 1) and ATF6 (activating transcription factor 6). The present study shows that ASNS (asparagine synthetase) transcription activity was up-regulated in HepG2 cells treated with the UPR activators thapsigargin and tunicamycin. ChIP (chromatin immunoprecipitation) analysis demonstrated that during ER stress, ATF4, ATF3 and C/EBPβ (CCAAT/enhancer-binding protein β) bind to the ASNS proximal promoter region that includes the genomic sequences NSRE (nutrient-sensing response element)-1 and NSRE-2, previously implicated by mutagenesis in UPR activation. Consistent with increased ASNS transcription, ChIP analysis also demonstrated that UPR signalling resulted in enhanced recruitment of general transcription factors, including RNA Pol II (polymerase II), to the ASNS promoter. The ASNS gene is also activated by the AAR (amino acid response) pathway following amino acid deprivation of tissue or cells. Immunoblot analysis of HepG2 cells demonstrated that simultaneous activation of the AAR and UPR pathways did not further increase the ASNS or ATF4 protein abundance when compared with triggering either pathway alone. In addition, siRNA (small interfering RNA)-mediated knockdown of XBP1 (X-box-binding protein 1), ATF6α or ATF6β expression did not affect ASNS transcription, whereas siRNA against ATF4 suppressed ASNS transcription during UPR activation. Collectively, these results indicate that the PERK/p-eIF2α (phosphorylated eukaryotic initiation factor 2α)/ATF4 signalling cascade is the only arm of the UPR that is responsible for ASNS transcriptional induction during ER stress. Consequently, ASNS NSRE-1 and NSRE-2, in addition to ERSE (ER stress response element)-I, ERSE-II and the mUPRE (mammalian UPR element), function as mammalian ER-stress-responsive sequences.

scholarly journals The Unfolded Protein Response Is a Major Driver of LCN2 Expression in BCR–ABL- and JAK2V617F-Positive MPN

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4210
Author(s):  
Stefan Tillmann ◽  
Kathrin Olschok ◽  
Sarah K. Schröder ◽  
Marlena Bütow ◽  
Julian Baumeister ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Molecular Mechanisms ◽  
Mononuclear Cells ◽  
Myeloproliferative Neoplasms ◽  
Serum Levels ◽  
Lipocalin 2 ◽  
Unfolded Protein ◽  
Main Driver ◽  
The Unfolded Protein Response ◽  
Protein Response

Lipocalin 2 (LCN2), a proinflammatory mediator, is involved in the pathogenesis of myeloproliferative neoplasms (MPN). Here, we investigated the molecular mechanisms of LCN2 overexpression in MPN. LCN2 mRNA expression was 20-fold upregulated in peripheral blood (PB) mononuclear cells of chronic myeloid leukemia (CML) and myelofibrosis (MF) patients vs. healthy controls. In addition, LCN2 serum levels were significantly increased in polycythemia vera (PV) and MF and positively correlated with JAK2V617F and mutated CALR allele burden and neutrophil counts. Mechanistically, we identified endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) as a main driver of LCN2 expression in BCR-ABL- and JAK2V617F-positive 32D cells. The UPR inducer thapsigargin increased LCN2 expression >100-fold, and this was not affected by kinase inhibition of BCR-ABL or JAK2V617F. Interestingly, inhibition of the UPR regulators inositol-requiring enzyme 1 (IRE1) and c-Jun N-terminal kinase (JNK) significantly reduced thapsigargin-induced LCN2 RNA and protein expression, and luciferase promoter assays identified nuclear factor kappa B (NF-κB) and CCAAT binding protein (C/EBP) as critical regulators of mLCN2 transcription. In conclusion, the IRE1–JNK-NF-κB–C/EBP axis is a major driver of LCN2 expression in MPN, and targeting UPR and LCN2 may represent a promising novel therapeutic approach in MPN.

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