scholarly journals UPR-Mediated Membrane Biogenesis in B Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Joseph W. Brewer ◽  
Suzanne Jackowski
Keyword(s):  
B Cells ◽  
Lipid Synthesis ◽  
Protein Translation ◽  
Secretory Proteins ◽  
Membrane Biogenesis ◽  
Unfolded Protein ◽  
Client Proteins ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
The Impact

The unfolded protein response (UPR) can coordinate the regulation of gene transcription and protein translation to balance the load of client proteins with the protein folding and degradative capacities of the ER. Increasing evidence also implicates the UPR in the regulation of lipid synthesis and membrane biogenesis. The differentiation of B lymphocytes into antibody-secreting cells is marked by significant expansion of the ER, the site for antibody synthesis and assembly. In activated B cells, the demand for membrane protein and lipid components leads to activation of the UPR transcriptional activator XBP1(S) which, in turn, initiates a cascade of biochemical events that enhance supplies of phospholipid precursors and build machinery for the synthesis, maturation, and transport of secretory proteins. The alterations in lipid metabolism that occur during this developmental transition and the impact of membrane phospholipid restriction on B cell secretory characteristics are discussed in this paper.

scholarly journals The unfolded protein response coordinates the production of endoplasmic reticulum protein and endoplasmic reticulum membrane.

1997 ◽  
Vol 8 (9) ◽  
pp. 1805-1814 ◽  
Author(s):  
J S Cox ◽  
R E Chapman ◽  
P Walter
Keyword(s):  
Endoplasmic Reticulum ◽  
Unfolded Protein Response ◽  
Secretory Pathway ◽  
Lipid Synthesis ◽  
Secretory Proteins ◽  
Endoplasmic Reticulum Membrane ◽  
Yeast Saccharomyces Cerevisiae ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

The endoplasmic reticulum (ER) is a multifunctional organelle responsible for production of both lumenal and membrane components of secretory pathway compartments. Secretory proteins are folded, processed, and sorted in the ER lumen and lipid synthesis occurs on the ER membrane itself. In the yeast Saccharomyces cerevisiae, synthesis of ER components is highly regulated: the ER-resident proteins by the unfolded protein response and membrane lipid synthesis by the inositol response. We demonstrate that these two responses are intimately linked, forming different branches of the same pathway. Furthermore, we present evidence indicating that this coordinate regulation plays a role in ER biogenesis.

scholarly journals The Endoplasmic Reticulum Role in the Plant Response to Abiotic Stress

2021 ◽  
Vol 12 ◽  
Author(s):  
Sofía Reyes-Impellizzeri ◽  
Adrian A. Moreno
Keyword(s):  
Endoplasmic Reticulum ◽  
Plant Response ◽  
Er Quality Control ◽  
Unfolded Protein ◽  
A Cell ◽  
Client Proteins ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
The Impact ◽  
S Proteins

The endoplasmic reticulum (ER) is the organelle where one third of the proteins of a cell are synthetized. Several of these proteins participate in the signaling and response of cells, tissues, or from the organism to the environment. To secure the proper synthesis and folding of these proteins, or the disposal of unfolded or misfolded proteins, the ER has different mechanisms that interact and regulate each other. These mechanisms are known as the ER quality control (ERQC), ER-associated degradation (ERAD) and the unfolded protein response (UPR), all three participants of the maintenance of ER protein homeostasis or proteostasis. Given the importance of the client proteins of these ER mechanisms in the plant response to the environment, it is expected that changes or alterations on their components have an impact on the plant response to environmental cues or stresses. In this mini review, we focus on the impact of the alteration of components of ERQC, ERAD and UPR in the plant response to abiotic stresses such as drought, heat, osmotic, salt and irradiation. Also, we summarize findings from recent publications looking for a connection between these processes and their possible client(s) proteins. From this, we observed that a clear connection has been established between the ERAD and UPR mechanisms, but evidence that connects ERQC components to these both processes or their possible client(s) proteins is still lacking. As a proposal, we suggest the use of proteomics approaches to uncover the identity of these proteins and their connection with ER proteostasis.

scholarly journals Reduced DNAJC3 Expression Affects Protein Translocation across the ER Membrane and Attenuates the Down-Modulating Effect of the Translocation Inhibitor Cyclotriazadisulfonamide

2022 ◽  
Vol 23 (2) ◽  
pp. 584
Author(s):  
Eva Pauwels ◽  
Becky Provinciael ◽  
Anita Camps ◽  
Enno Hartmann ◽  
Kurt Vermeire
Keyword(s):  
Protein Translocation ◽  
Combined Treatment ◽  
Protein Translation ◽  
Reporter Protein ◽  
Protein Levels ◽  
Unfolded Protein ◽  
Enhanced Sensitivity ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
The Impact

One of the reported substrates for the endoplasmic reticulum (ER) translocation inhibitor cyclotriazadisulfonamide (CADA) is DNAJC3, a chaperone of the unfolded protein response during ER stress. In this study, we investigated the impact of altered DNAJC3 protein levels on the inhibitory activity of CADA. By comparing WT DNAJC3 with a CADA-resistant DNAJC3 mutant, we observed the enhanced sensitivity of human CD4, PTK7 and ERLEC1 for CADA when DNAJC3 was expressed at high levels. Combined treatment of CADA with a proteasome inhibitor resulted in synergistic inhibition of protein translocation and in the rescue of a small preprotein fraction, which presumably corresponds to the CADA affected protein fraction that is stalled at the Sec61 translocon. We demonstrate that DNAJC3 enhances the protein translation of a reporter protein that is expressed downstream of the CADA-stalled substrate, suggesting that DNAJC3 promotes the clearance of the clogged translocon. We propose a model in which a reduced DNAJC3 level by CADA slows down the clearance of CADA-stalled substrates. This results in higher residual translocation into the ER lumen due to the longer dwelling time of the temporarily stalled substrates in the translocon. Thus, by directly reducing DNAJC3 protein levels, CADA attenuates its net down-modulating effect on its substrates.

scholarly journals Beyond the cell factory: Homeostatic regulation of and by the UPRER

2020 ◽  
Vol 6 (29) ◽  
pp. eabb9614
Author(s):  
Melissa G. Metcalf ◽  
Ryo Higuchi-Sanabria ◽  
Gilberto Garcia ◽  
C. Kimberly Tsui ◽  
Andrew Dillin
Keyword(s):  
Protein Misfolding ◽  
Lipid Synthesis ◽  
Transcriptional Response ◽  
Cell Factory ◽  
Unfolded Protein ◽  
Membrane Bound ◽  
Emerging Themes ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Cellular Components

The endoplasmic reticulum (ER) is commonly referred to as the factory of the cell, as it is responsible for a large amount of protein and lipid synthesis. As a membrane-bound organelle, the ER has a distinct environment that is ideal for its functions in synthesizing these primary cellular components. Many different quality control machineries exist to maintain ER stability under the stresses associated with synthesizing, folding, and modifying complex proteins and lipids. The best understood of these mechanisms is the unfolded protein response of the ER (UPRER), in which transmembrane proteins serve as sensors, which trigger a coordinated transcriptional response of genes dedicated for mitigating the stress. As the name suggests, the UPRER is most well described as a functional response to protein misfolding stress. Here, we focus on recent findings and emerging themes in additional roles of the UPRER outside of protein homeostasis, including lipid homeostasis, autophagy, apoptosis, and immunity.

scholarly journals Emerging Roles of the Endoplasmic Reticulum Associated Unfolded Protein Response in Cancer Cell Migration and Invasion

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 631 ◽  
Author(s):  
Celia Limia ◽  
Chloé Sauzay ◽  
Hery Urra ◽  
Claudio Hetz ◽  
Eric Chevet ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Migration ◽  
Unfolded Protein Response ◽  
Protein Translation ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion ◽  
Unfolded Protein ◽  
Protein Response ◽  
The Impact

Endoplasmic reticulum (ER) proteostasis is often altered in tumor cells due to intrinsic (oncogene expression, aneuploidy) and extrinsic (environmental) challenges. ER stress triggers the activation of an adaptive response named the Unfolded Protein Response (UPR), leading to protein translation repression, and to the improvement of ER protein folding and clearance capacity. The UPR is emerging as a key player in malignant transformation and tumor growth, impacting on most hallmarks of cancer. As such, the UPR can influence cancer cells’ migration and invasion properties. In this review, we overview the involvement of the UPR in cancer progression. We discuss its cross-talks with the cell migration and invasion machinery. Specific aspects will be covered including extracellular matrix (ECM) remodeling, modification of cell adhesion, chemo-attraction, epithelial-mesenchymal transition (EMT), modulation of signaling pathways associated with cell mobility, and cytoskeleton remodeling. The therapeutic potential of targeting the UPR to treat cancer will also be considered with specific emphasis in the impact on metastasis and tissue invasion.

scholarly journals The LMP1 oncogene of EBV activates PERK and the unfolded protein response to drive its own synthesis

Blood ◽  
2008 ◽  
Vol 111 (4) ◽  
pp. 2280-2289 ◽  
Author(s):  
Dong Yun Lee ◽  
Bill Sugden
Keyword(s):  
B Cells ◽  
Unfolded Protein Response ◽  
Threshold Level ◽  
Initiation Factor ◽  
Barr Virus ◽  
Unfolded Protein ◽  
General Protein Synthesis ◽  
Epstein Barr ◽  
The Unfolded Protein Response ◽  
Protein Response

The oncogene latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) without a ligand drives proliferation of EBV-infected B cells. Its levels vary in cells of clonal populations by more than 100-fold, which leads to multiple distinct activities of the oncogene. At intermediate levels it drives proliferation, and at high levels it inhibits general protein synthesis by inducing phosphorylation of eukaryotic initiation factor 2α (eIF2α). We have found that LMP1 activates PERK to induce phosphorylation of eIF2α, which upregulates activating transcription factor 4 (ATF4) expression. ATF4, in turn, transactivates LMP1's own promoter. LMP1 activates not only PERK but also inositol requiring kinase 1 (IRE1) and ATF6, 3 pathways of the unfolded protein response (UPR). Increasing expression levels of LMP1 induced a dose-dependent increase in IRE1 activity, as measured by its “splicing” of XBP-1. These infected B cells secrete immunoglobins independent of the levels of LMP1, indicating that only a threshold level of XBP-1 is required for the secretion. These findings indicate that LMP1's activation of the UPR is a normal event in a continuum of LMP1's expression that leads both to stimulatory and inhibitory functions and regulates the physiology of EBV-infected B cells in multiple, unexpected modes.

scholarly journals Unfolded Protein Response as a Therapeutic Target in Cardiovascular Disease

2019 ◽  
Vol 19 (21) ◽  
pp. 1902-1917 ◽  
Author(s):  
Guangyu Zhang ◽  
Xiaoding Wang ◽  
Thomas G. Gillette ◽  
Yingfeng Deng ◽  
Zhao V. Wang
Keyword(s):  
Cardiovascular Disease ◽  
Protein Folding ◽  
Unfolded Protein Response ◽  
Protein Translation ◽  
Ample Evidence ◽  
Unfolded Protein ◽  
Er Stress Response ◽  
Chronic Disturbance ◽  
The Unfolded Protein Response ◽  
Protein Response

Cardiovascular disease is the leading cause of death worldwide. Despite overwhelming socioeconomic impact and mounting clinical needs, our understanding of the underlying pathophysiology remains incomplete. Multiple forms of cardiovascular disease involve an acute or chronic disturbance in cardiac myocytes, which may lead to potent activation of the Unfolded Protein Response (UPR), a cellular adaptive reaction to accommodate protein-folding stress. Accumulation of unfolded or misfolded proteins in the Endoplasmic Reticulum (ER) elicits three signaling branches of the UPR, which otherwise remain quiescent. This ER stress response then transiently suppresses global protein translation, augments production of protein-folding chaperones, and enhances ER-associated protein degradation, with an aim to restore cellular homeostasis. Ample evidence has established that the UPR is strongly induced in heart disease. Recently, the mechanisms of action and multiple pharmacological means to favorably modulate the UPR are emerging to curb the initiation and progression of cardiovascular disease. Here, we review the current understanding of the UPR in cardiovascular disease and discuss existing therapeutic explorations and future directions.

scholarly journals The Impact of Endoplasmic Reticulum-Associated Protein Modifications, Folding and Degradation on Lung Structure and Function

2021 ◽  
Vol 12 ◽  
Author(s):  
Emily M. Nakada ◽  
Rui Sun ◽  
Utako Fujii ◽  
James G. Martin
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Unfolded Protein ◽  
Lung Structure ◽  
Selective Translation ◽  
The Unfolded Protein Response ◽  
And Function ◽  
Protein Response ◽  
Er Homeostasis ◽  
The Impact

The accumulation of unfolded/misfolded proteins in the endoplasmic reticulum (ER) causes ER stress and induces the unfolded protein response (UPR) and other mechanisms to restore ER homeostasis, including translational shutdown, increased targeting of mRNAs for degradation by the IRE1-dependent decay pathway, selective translation of proteins that contribute to the protein folding capacity of the ER, and activation of the ER-associated degradation machinery. When ER stress is excessive or prolonged and these mechanisms fail to restore proteostasis, the UPR triggers the cell to undergo apoptosis. This review also examines the overlooked role of post-translational modifications and their roles in protein processing and effects on ER stress and the UPR. Finally, these effects are examined in the context of lung structure, function, and disease.

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