scholarly journals Dual role of the integrated stress response in medulloblastoma tumorigenesis

Oncotarget ◽  
2016 ◽  
Vol 7 (39) ◽  
pp. 64124-64135 ◽  
Author(s):  
Sarrabeth Stone ◽  
Yeung Ho ◽  
Xiting Li ◽  
Stephanie Jamison ◽  
Heather P. Harding ◽  
...  
Keyword(s):  
Stress Response ◽  
Dual Role ◽  
Integrated Stress Response

scholarly journals Dual Role of the Histone Variant H2A.Z in Transcriptional Regulation of Stress-Response Genes

2017 ◽  
Vol 29 (4) ◽  
pp. 791-807 ◽  
Author(s):  
Weronika Sura ◽  
Michał Kabza ◽  
Wojciech M. Karlowski ◽  
Tomasz Bieluszewski ◽  
Marta Kus-Slowinska ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Stress Response ◽  
Dual Role ◽  
Histone Variant ◽  
Stress Response Genes

Abstract A32: The role of the ribosome in GCN2's ability to sense amino acid deprivation and initiate the integrated stress response

2017 ◽  
Author(s):  
Alison J. Inglis ◽  
Sichen Shao ◽  
Glenn R. Masson ◽  
Olga Perisic ◽  
Ramanujan S. Hegde ◽  
...  
Keyword(s):  
Amino Acid ◽  
Stress Response ◽  
Integrated Stress Response ◽  
Amino Acid Deprivation

scholarly journals Integrated Stress Response as a Therapeutic Target for CNS Injuries

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Lorenzo Romero-Ramírez ◽  
Manuel Nieto-Sampedro ◽  
M. Asunción Barreda-Manso
Keyword(s):  
Central Nervous System ◽  
Stress Response ◽  
Small Molecules ◽  
Therapeutic Target ◽  
Protective Mechanism ◽  
Diverse Group ◽  
Integrated Stress Response ◽  
Cns Injury ◽  
Injury Repair

Central nervous system (CNS) injuries, caused by cerebrovascular pathologies or mechanical contusions (e.g., traumatic brain injury, TBI) comprise a diverse group of disorders that share the activation of the integrated stress response (ISR). This pathway is an innate protective mechanism, with encouraging potential as therapeutic target for CNS injury repair. In this review, we will focus on the progress in understanding the role of the ISR and we will discuss the effects of various small molecules that target the ISR on different animal models of CNS injury.

scholarly journals Heme-regulated eIF2α kinase in erythropoiesis and hemoglobinopathies

Blood ◽  
2019 ◽  
Vol 134 (20) ◽  
pp. 1697-1707 ◽  
Author(s):  
Jane-Jane Chen ◽  
Shuping Zhang
Keyword(s):  
Protein Synthesis ◽  
Stress Response ◽  
Initiation Factor ◽  
Integrated Stress Response ◽  
Iron Availability ◽  
Eukaryotic Initiation Factor ◽  
Erythroid Cells ◽  
Eif2α Kinase ◽  
In Erythroid Cells

Chen and Zhang review the role of eukaryotic initiation factor 2α (eIF2α) in regulating the balance between protein synthesis and iron availability as part of the integrated stress response in erythroid cells.

scholarly journals Integrated stress response restricts macrophage necroptosis

2021 ◽  
Vol 5 (1) ◽  
pp. e202101260
Author(s):  
David E Place ◽  
Parimal Samir ◽  
RK Subbarao Malireddi ◽  
Thirumala-Devi Kanneganti
Keyword(s):  
Cell Death ◽  
Stress Response ◽  
Cell Survival ◽  
Stress Responses ◽  
Critical Role ◽  
Stress Granule ◽  
Integrated Stress Response ◽  
Signaling Axis ◽  
Stressed Cells

The integrated stress response (ISR) regulates cellular homeostasis and cell survival following exposure to stressors. Cell death processes such as apoptosis and pyroptosis are known to be modulated by stress responses, but the role of the ISR in necroptosis is poorly understood. Necroptosis is an inflammatory, lytic form of cell death driven by the RIPK3-MLKL signaling axis. Here, we show that macrophages that have induced the ISR are protected from subsequent necroptosis. Consistent with a reduction in necroptosis, phosphorylation of RIPK1, RIPK3, and MLKL is reduced in macrophages pre-treated with ISR-inducing agents that are challenged with necroptosis-inducing triggers. The stress granule component DDX3X, which is involved in ISR-mediated regulation of pyroptosis, is not required for protecting ISR-treated cells from necroptosis. Disruption of stress granule assembly or knockdown of Perk restored necroptosis in pre-stressed cells. Together, these findings identify a critical role for the ISR in limiting necroptosis in macrophages.

Abstract 2072: The role of the integrated stress response proteins GCN2 and ATF4 in autophagy and tumor migration

2011 ◽  
Author(s):  
Stacey L. Lehman ◽  
Carly M. Sayers ◽  
Jiangbin Ye ◽  
Lori S. Hart ◽  
Deborah O. Ayeni ◽  
...  
Keyword(s):  
Stress Response ◽  
Integrated Stress Response ◽  
Stress Response Proteins

scholarly journals The Fragile X Mental Retardation Protein protects the lung from xenobiotic stress by facilitating the Integrated Stress Response

2021 ◽  
Author(s):  
Deblina Sain Basu ◽  
Rital Bhavsar ◽  
Imtiyaz Gulami ◽  
Saimanoz Lingamallu ◽  
Ravi Muddashetty ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Stress Response ◽  
Stress Responses ◽  
Fragile X ◽  
Air Pollutant ◽  
Environmental Toxicants ◽  
Integrated Stress Response ◽  
Fragile X Mental Retardation ◽  
Mental Retardation Protein

Stress response pathways protect the lung from the damaging effects of environmental toxicants. Here we investigate the role of the Fragile X Mental Retardation Protein (FMRP), a multifunctional protein implicated in stress responses, in the lung. We report that FMRP is expressed in murine and human lungs, in the airways and more broadly. Analysis of airway stress responses in mice and in a murine cell line ex vivo, using the well-established Naphthalene (Nap) injury model, reveals that FMRP-deficient cells exhibit increased expression of markers of oxidative and genotoxic stress and increased cell death. We find that FMRP-deficient cells fail to actuate the Integrated Stress Response Pathway (ISR) and upregulate the transcription factor ATF4. Knockdown of ATF4 expression phenocopies the loss of FMRP. We extend our analysis of the role of FMRP to human bronchial BEAS-2B cells, using a 9, 10-Phenanthrenequinone air pollutant model, to find that FMRP-deficient BEAS-2B also fail to actuate the ISR and exhibit greater susceptibility. Taken together, our data suggest that FMRP has a conserved role in protecting the airways by facilitating the ISR.

scholarly journals Mutagenesis screen uncovers lifespan extension through integrated stress response inhibition without reduced mRNA translation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Maxime J. Derisbourg ◽  
Laura E. Wester ◽  
Ruth Baddi ◽  
Martin S. Denzel
Keyword(s):  
Stress Response ◽  
Translation Initiation ◽  
Mrna Translation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Lifespan Extension ◽  
Protein Homeostasis ◽  
Integrated Stress Response ◽  
Mutagenesis Screen

AbstractProtein homeostasis is modulated by stress response pathways and its deficiency is a hallmark of aging. The integrated stress response (ISR) is a conserved stress-signaling pathway that tunes mRNA translation via phosphorylation of the translation initiation factor eIF2. ISR activation and translation initiation are finely balanced by eIF2 kinases and by the eIF2 guanine nucleotide exchange factor eIF2B. However, the role of the ISR during aging remains poorly understood. Using a genomic mutagenesis screen for longevity inCaenorhabditis elegans, we define a role of eIF2 modulation in aging. By inhibiting the ISR, dominant mutations in eIF2B enhance protein homeostasis and increase lifespan. Consistently, full ISR inhibition using phosphorylation-defective eIF2α or pharmacological ISR inhibition prolong lifespan. Lifespan extension through impeding the ISR occurs without a reduction in overall protein synthesis. Instead, we observe changes in the translational efficiency of a subset of mRNAs, of which the putative kinasekin-35is required for lifespan extension. Evidently, lifespan is limited by the ISR and its inhibition may provide an intervention in aging.

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