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 Complementary Signaling Pathways Regulate the Unfolded Protein Response and Are Required for C. elegans Development

Cell ◽  
2001 ◽  
Vol 107 (7) ◽  
pp. 893-903 ◽  
Author(s):  
Xiaohua Shen ◽  
Ronald E. Ellis ◽  
Kyungho Lee ◽  
Chuan-Yin Liu ◽  
Kun Yang ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Signaling Pathways ◽  
C Elegans ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals Parallel signaling through IRE1α and PERK regulates pancreatic neuroendocrine tumor growth and survival

2019 ◽  
Author(s):  
Paul C. Moore ◽  
Jenny Y. Qi ◽  
Maike Thamsen ◽  
Rajarshi Ghosh ◽  
Justin Peng ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Neuroendocrine Tumors ◽  
Cultured Cells ◽  
Pancreatic Neuroendocrine Tumors ◽  
Growth And Survival ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

AbstractMaster regulators of the unfolded protein response (UPR)—IRE1α and PERK— promote adaptation or apoptosis depending on levels of endoplasmic reticulum (ER) stress. While the UPR is activated in many cancers, its effects on tumor growth remain unclear. Derived from endocrine cells, pancreatic neuroendocrine tumors (PanNETs) universally hypersecrete one or more peptide hormones, likely sensitizing these cells to high ER protein-folding stress. For the nearly 1,500 Americans diagnosed with PanNETs annually, surgery is the only potentially curative treatment; however the five-year survival is extremely low for those who develop metastatic disease. To assess whether targeting the UPR is a viable therapeutic strategy, we analyzed human PanNET samples and found evidence of elevated ER stress and UPR activation. We then used genetic and pharmacologic approaches to modulate IRE1α and PERK in cultured cells and xenograft and spontaneous genetic (RIP-Tag2) mouse models of PanNETs. We found that UPR signaling is optimized for adaptation and that inhibiting either IRE1α or PERK leads to hyperactivation and apoptotic signaling through the reciprocal arm, thereby halting tumor growth and survival. Our results provide a strong rationale for therapeutically targeting the UPR in PanNETs and other cancers experiencing elevated ER stress.SignificanceThe unfolded protein response (UPR) is upregulated in human pancreatic neuroendocrine tumors and its genetic or pharmacological inhibition significantly reduces tumor growth in preclinical models, providing strong rationale for targeting the UPR in neoplasms with elevated ER stress.

scholarly journals Silence without stress

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
David J Young ◽  
Nicholas R Guydosh
Keyword(s):  
Transcription Factor ◽  
Unfolded Protein Response ◽  
Protein A ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

Two mechanisms ensure that the mRNA encoding Hac1 protein, a transcription factor involved in the unfolded protein response, is only translated when it is needed.

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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