Yeast Gcn2 retains activity following humanization of its auto-phosphorylation region. [PDF]
FEBS Open BioUsing Saccharomyces cerevisiae as a model to study Gcn2 activation and regulation is limited by the lack of antibodies detecting phosphorylated Gcn2. To overcome this, we engineered Gcn2‐HsC, a yeast Gcn2 variant recognizable by commercial anti‐human phospho‐GCN2 antibodies.
Anderson RA, Schiemann AH, Sattlegger E.
europepmc +2 more sources
Redox Biology, 2022 The development of nonalcoholic fatty liver disease (NAFLD) is associated with increased reactive oxygen species (ROS) production. Previous observations on the contradictory roles of general control nonderepressible 2 (GCN2) in regulating the hepatic ...
Zhongbing Lu, Kai Luo
exaly +3 more sources
The antitumor activity of a novel GCN2 inhibitor in head and neck squamous cell carcinoma cell lines
Translational Oncology, 2023 Background: General control nonderepressible 2 (GCN2) senses amino acid deprivation and activates activating transcription factor 4 (ATF4), which regulates many adaptive genes. We evaluated the impact of AST-0513, a novel GCN2 inhibitor, on the GCN2-ATF4
Dong-Wan Kim, Dae Seog Heo, Tae Min Kim
exaly +3 more sources
RAF inhibitors activate the integrated stress response by direct activation of GCN2 [PDF]
Nature CommunicationsParadoxical activation of wild type RAF by chemical RAF inhibitors (RAFi) is a well-understood ‘on-target’ biological and clinical response. In this study, we show that a range of RAFi drive ERK1/2-independent activation of the Unfolded Protein Response (
Rebecca Gilley +13 more
doaj +2 more sources
Salmonella Typhi asparaginase-dependent activation of GCN2 promotes bacterial killing in murine macrophages [PDF]
Infection and ImmunityMany intracellular pathogens stimulate host cell stress by directly or indirectly causing an imbalance in host nutrients. Depletion of amino acid pools, in particular, can act as a danger signal to infected cells.
Zachary M. Powers +10 more
doaj +2 more sources
GCN2 enhances host survival and drives eIF2α phosphorylation during mouse adenovirus type 1 infection [PDF]
Journal of VirologyThe integrated stress response (ISR) is a cellular signaling pathway that reduces protein synthesis in the face of cellular stress, including viral infection. Two eukaryotic initiation factor 2α (eIF2α) kinases, protein kinase R (PKR) and general control
Luiza A. Castro Jorge +6 more
doaj +2 more sources
GCN2 is activated by methyl jasmonate through GCN1 and reactive oxygen species in Arabidopsis thaliana [PDF]
Scientific ReportsPlant growth and productivity rely on rapid energy management strategies to adapt dynamic environments. Previous work in Arabidopsis thaliana identified a fast-regulatory switch linking cytosolic translation and reactive oxygen species (ROS) signaling ...
Daniel Rincon Diaz +4 more
doaj +2 more sources
A genetic approach to identify amino acids in Gcn1 required for Gcn2 activation.
PLoS ONE, 2022 The protein kinase Gcn2 is present in virtually all eukaryotic cells. It is best known for its role in helping cells cope with amino acid starvation. Under starvation, Gcn2 phosphorylates the α subunit of the eukaryotic translation initiation factor 2 ...
Susanne Gottfried +4 more
doaj +2 more sources
Modulation of GCN2 activity under excess light stress by osmoprotectants and amino acids
Plant Signaling & Behavior, 2022 The protein kinase GCN2 (General Control Nonderepressible2) and its phosphorylation target, the eukaryotic translation initiation factor (eIF)2α represent the core module of the plant’s integrated stress response, a signaling pathway widely conserved in ...
Ansul Lokdarshi +2 more
doaj +1 more source
Dengue Virus Induced COX-2 Signaling Is Regulated Through Nutrient Sensor GCN2
Frontiers in Immunology, 2020 Nutrient sensor GCN2 plays a crucial role in the maintenance of cellular homeostasis during the condition of amino acid deprivation. Dysfunction in the GCN2 signaling underlies several chronic metabolic diseases.
Sumbul Afroz +5 more
doaj +1 more source