scholarly journals CPR5 modulates salicylic acid and the unfolded protein response to manage tradeoffs between plant growth and stress responses

2017 ◽  
Vol 89 (3) ◽  
pp. 486-501 ◽  
Author(s):  
Zhe Meng ◽  
Cristina Ruberti ◽  
Zhizhong Gong ◽  
Federica Brandizzi
Keyword(s):  
Salicylic Acid ◽  
Plant Growth ◽  
Unfolded Protein Response ◽  
Stress Responses ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals Herpesviruses and the Unfolded Protein Response

Viruses ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 17 ◽  
Author(s):  
Benjamin P. Johnston ◽  
Craig McCormick
Keyword(s):  
Unfolded Protein Response ◽  
Stress Responses ◽  
Immune Surveillance ◽  
Lytic Replication ◽  
Glycoprotein Synthesis ◽  
Unfolded Protein ◽  
Transcriptional Reprogramming ◽  
Molecular Events ◽  
The Unfolded Protein Response ◽  
Protein Response

Herpesviruses usurp cellular stress responses to promote viral replication and avoid immune surveillance. The unfolded protein response (UPR) is a conserved stress response that is activated when the protein load in the ER exceeds folding capacity and misfolded proteins accumulate. The UPR aims to restore protein homeostasis through translational and transcriptional reprogramming; if homeostasis cannot be restored, the UPR switches from “helper” to “executioner”, triggering apoptosis. It is thought that the burst of herpesvirus glycoprotein synthesis during lytic replication causes ER stress, and that these viruses may have evolved mechanisms to manage UPR signaling to create an optimal niche for replication. The past decade has seen considerable progress in understanding how herpesviruses reprogram the UPR. Here we provide an overview of the molecular events of UPR activation, signaling and transcriptional outputs, and highlight key evidence that herpesviruses hijack the UPR to aid infection.

Exogenous Salicylic Acid Activates Two Signaling Arms of the Unfolded Protein Response in Arabidopsis

2014 ◽  
Vol 55 (10) ◽  
pp. 1772-1778 ◽  
Author(s):  
Yukihiro Nagashima ◽  
Yuji Iwata ◽  
Makoto Ashida ◽  
Kei-ichiro Mishiba ◽  
Nozomu Koizumi
Keyword(s):  
Salicylic Acid ◽  
Unfolded Protein Response ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Exogenous Salicylic Acid

scholarly journals Regulation of the unfolded protein response by noncoding RNA

2017 ◽  
Vol 313 (3) ◽  
pp. C243-C254 ◽  
Author(s):  
Mari McMahon ◽  
Afshin Samali ◽  
Eric Chevet
Keyword(s):  
Unfolded Protein Response ◽  
Stress Responses ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Small Noncoding Rna ◽  
Downstream Signaling ◽  
Unfolded Protein ◽  
Cell Death Mechanisms ◽  
The Unfolded Protein Response ◽  
Protein Response

Cells are exposed to various intrinsic and extrinsic stresses in both physiological and pathological conditions. To adapt to those conditions, cells have evolved various mechanisms to cope with the disturbances in protein demand, largely through the unfolded protein response (UPR) in the endoplasmic reticulum (ER), but also through the integrated stress response (ISR). Both responses initiate downstream signaling to transcription factors that, in turn, trigger adaptive programs and/or in the case of prolonged stress, cell death mechanisms. Recently, noncoding RNAs, including microRNA and long noncoding RNA, have emerged as key players in the stress responses. These noncoding RNAs act as both regulators and effectors of the UPR and fine-tune the output of the stress signaling pathways. Although much is known about the UPR and the cross talk that exists between pathways, the contribution of small noncoding RNA has not been fully assessed. Herein we bring together and review the current known functions of noncoding RNA in regulating adaptive pathways in both physiological and pathophysiological conditions, illustrating how they operate within the known UPR functions and contribute to diverse cellular outcomes.

scholarly journals Salicylic acid-independent role of NPR1 is required for protection from proteotoxic stress in the plant endoplasmic reticulum

2018 ◽  
Vol 115 (22) ◽  
pp. E5203-E5212 ◽  
Author(s):  
Ya-Shiuan Lai ◽  
Luciana Renna ◽  
John Yarema ◽  
Cristina Ruberti ◽  
Sheng Yang He ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Salicylic Acid ◽  
Er Stress ◽  
Stress Responses ◽  
Unfolded Protein ◽  
Redox Activation ◽  
Genetic Level ◽  
The Unfolded Protein Response ◽  
Protein Response

The unfolded protein response (UPR) is an ancient signaling pathway designed to protect cells from the accumulation of unfolded and misfolded proteins in the endoplasmic reticulum (ER). Because misregulation of the UPR is potentially lethal, a stringent surveillance signaling system must be in place to modulate the UPR. The major signaling arms of the plant UPR have been discovered and rely on the transcriptional activity of the transcription factors bZIP60 and bZIP28 and on the kinase and ribonuclease activity of IRE1, which splices mRNA to activate bZIP60. Both bZIP28 and bZIP60 modulate UPR gene expression to overcome ER stress. In this study, we demonstrate at a genetic level that the transcriptional role of bZIP28 and bZIP60 in ER-stress responses is antagonized by nonexpressor of PR1 genes 1 (NPR1), a critical redox-regulated master regulator of salicylic acid (SA)-dependent responses to pathogens, independently of its role in SA defense. We also establish that the function of NPR1 in the UPR is concomitant with ER stress-induced reduction of the cytosol and translocation of NPR1 to the nucleus where it interacts with bZIP28 and bZIP60. Our results support a cellular role for NPR1 as well as a model for plant UPR regulation whereby SA-independent ER stress-induced redox activation of NPR1 suppresses the transcriptional role of bZIP28 and bZIP60 in the UPR.

scholarly journals Stress Management: Death Receptor Signalling and Cross-Talks with the Unfolded Protein Response in Cancer

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1113 ◽  
Author(s):  
Elodie Lafont
Keyword(s):  
Unfolded Protein Response ◽  
Stress Responses ◽  
Tumour Progression ◽  
Death Receptor ◽  
Tumour Cells ◽  
Unfolded Protein ◽  
Extrinsic Cues ◽  
Molecular Determinants ◽  
The Unfolded Protein Response ◽  
Protein Response

Throughout tumour progression, tumour cells are exposed to various intense cellular stress conditions owing to intrinsic and extrinsic cues, to which some cells are remarkably able to adapt. Death Receptor (DR) signalling and the Unfolded Protein Response (UPR) are two stress responses that both regulate a plethora of outcomes, ranging from proliferation, differentiation, migration, cytokine production to the induction of cell death. Both signallings are major modulators of physiological tissue homeostasis and their dysregulation is involved in tumorigenesis and the metastastic process. The molecular determinants of the control between the different cellular outcomes induced by DR signalling and the UPR in tumour cells and their stroma and their consequences on tumorigenesis are starting to be unravelled. Herein, I summarize the main steps of DR signalling in relation to its cellular and pathophysiological roles in cancer. I then highlight how the UPR and DR signalling control common cellular outcomes and also cross-talk, providing potential opportunities to further understand the development of malignancies.

Antioxidants Improve Factor VIII Secretion in the Liver by Preventing Oxidative Stress, Activation of the Unfolded Protein Response, and Apoptosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 197-197
Author(s):  
Jyoti D. Malhotra ◽  
Kezhong Zhang ◽  
Hongzi Miao ◽  
Steven W. Pipe ◽  
Randal J. Kaufman
Keyword(s):  
Oxidative Stress ◽  
Factor Viii ◽  
Unfolded Protein Response ◽  
Stress Responses ◽  
Factor V ◽  
Dna Encoding ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

Abstract Factor V (FV) and Factor VIII (FVIII) are homologous glycoproteins that provide essential functions in hemostasis. Previous studies demonstrated that compared to FV, the FVIII polypeptide folds inefficiently, accumulates in the endoplasmic reticulum (ER) and activates the Unfolded Protein Response (UPR). The UPR, mediated by the proximal sensors PERK and IRE1, is a signaling pathway leading to either adaptive survival or apoptotic demise upon accumulation of unfolded proteins in the ER. Here we show that FVIII expression in hepatocytes in vivo mediated by hydrodynamic tail-vein injection of plasmid DNA into fviii −/ − mice produces between 0.5 to 1.0 Unit/ml of FVIII in the plasma. This level of FVIII expression activated PERK and IRE1 to signal the UPR and induced both markers of oxidative stress and apoptosis in hepatocytes. In contrast, injection of DNA encoding either FV or a FVIII molecule engineered for improved secretion did not induce oxidative stress, activate the UPR or induce apoptosis. Gene expression analysis demonstrated that FVIII expression induced expression of the proapoptotic transcription factor CHOP. Injection of FVIII expression plasmids into chop−/ − mice did not induce oxidative stress or apoptosis, indicating that these stress responses require CHOP. Feeding of mice with the lipid soluble antioxidant, butylated hydroxy anisole (BHA), reduced oxidative stress and apoptosis and increased expression of FVIII in the plasma, demonstrating a pivotal role of oxidative stress in limiting FVIII expression and triggering apoptosis. Finally, overexpression of the anti-apoptotic protein Bcl2 also significantly suppressed oxidative stress and apoptosis and increased FVIII expression. The results demonstrate that 1) misfolding of an ER luminal protein, FVIII, is sufficient to induce oxidative stress and apoptosis in vivo, 2) oxidative stress limits protein secretion and activates apoptosis through a mechanism that requires CHOP, and 3) intervention to prevent oxidative stress by antioxidant feeding or Bcl2 overexpression preserves ER function, improves secretion and prevents apoptosis. The findings raise the possibility to treat diseases of protein misfolding, such as certain mutations that cause hemophilia A, by treatment with antioxidants.

scholarly journals Herpesviruses and the Unfolded Protein Response

2019 ◽  
Author(s):  
Benjamin P. Johnston ◽  
Craig McCormick
Keyword(s):  
Stress Response ◽  
Viral Replication ◽  
Unfolded Protein Response ◽  
Stress Responses ◽  
Cellular Stress ◽  
Cellular Stress Response ◽  
Negative Effects ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

Herpesviruses usurp cellular stress responses to avoid immune detection while simultaneously promoting viral replication and spread. The unfolded protein response (UPR) is an evolutionarily conserved stress response that is activated when the protein load in the ER saturates its chaperone folding capacity causing an accrual of misfolded proteins. Through translational and transcriptional reprogramming, the UPR aims to restore protein homeostasis; however, if this fails the cell undergoes apoptosis. It is commonly thought that many enveloped viruses, including herpesviruses, may activate the UPR due to saturation of the ER with nascent glycoproteins and thus these viruses may have evolved mechanisms to evade the potentially negative effects of UPR signaling. Over the past fifteen years there has been considerable effort to provide evidence that different viruses may reprogram the UPR to promote viral replication. Here we provide an overview of the molecular events of UPR activation, signaling and transcriptional outputs, and highlight key findings that demonstrate that the UPR is an important cellular stress response that herpesviruses have hijacked to facilitate persistent infection.

scholarly journals Disruption of ceramide synthesis by CerS2 down-regulation leads to autophagy and the unfolded protein response

2009 ◽  
Vol 424 (2) ◽  
pp. 273-283 ◽  
Author(s):  
Stefka D. Spassieva ◽  
Thomas D. Mullen ◽  
Danyelle M. Townsend ◽  
Lina M. Obeid
Keyword(s):  
Unfolded Protein Response ◽  
Stress Responses ◽  
Apoptotic Cell ◽  
Sphingolipid Metabolism ◽  
Ceramide Synthase ◽  
Down Regulation ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Long Chain

Ceramide metabolism has come under recent scrutiny because of its role in cellular stress responses. CerS2 (ceramide synthase 2) is one of the six mammalian isoforms of ceramide synthase and is responsible for the synthesis of VLC (very-long-chain) ceramides, e.g. C24, C24:1. To study the role of CerS2 in ceramide metabolism and cellular homoeostasis, we down-regulated CerS2 using siRNA (small interfering RNA) and examined several aspects of sphingolipid metabolism and cell stress responses. CerS2 down-regulation had a broad effect on ceramide homoeostasis, not just on VLC ceramides. Surprisingly, CerS2 down-regulation resulted in significantly increased LC (long-chain) ceramides, e.g. C14, C16, and our results suggested that the increase was due to a ceramide synthase-independent mechanism. CerS2-down-regulation-induced LC ceramide accumulation resulted in growth arrest which was not accompanied by apoptotic cell death. Instead, cells remained viable, showing induction of autophagy and activation of PERK [PKR (double-stranded-RNA-dependent protein kinase)-like endoplasmic reticulum kinase] and IRE1 (inositol-requiring 1) pathways [the latter indicating activation of the UPR (unfolded protein response)].

Sign in / Sign up

Export Citation Format

Share Document