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GCN2 Gcn2p

GCN2, Gcn2p
EIF2AK4 belongs to a family of kinases that phosphorylate the alpha subunit of eukaryotic translation initiation factor-2 (EIF2S1; MIM 603907) to downregulate protein synthesis in response to varied cellular stresses (Berlanga et al., 1999 [PubMed 10504407]).[supplied by OMIM, Mar 2008] (from NCBI)
Top mentioned proteins: ACID, eIF2alpha, CAN, PKR, V1a
Papers on GCN2
Angiopoietin-like protein 8 (betatrophin) is a stress-response protein that down-regulates expression of adipocyte triglyceride lipase.
Yang et al., Gainesville, United States. In Biochim Biophys Acta, Feb 2016
The activation of ANGPTL8 gene transcription was mediated through the RAS/c-RAF/MAPK signaling pathway rather than the general GCN2/ATF4 pathways.
Arginine starvation in colorectal carcinoma cells: Sensing, impact on translation control and cell cycle distribution.
Stasyk et al., L'viv, Ukraine. In Exp Cell Res, Feb 2016
The results presented herein state that human colorectal carcinoma cells rapidly exhaust the internal arginine sources in the absence of exogenous arginine and repress global translation by activation of the GCN2-mediated pathway and inhibition of mTOR signaling.
GCN2 sustains mTORC1 suppression upon amino acid deprivation by inducing Sestrin2.
Thompson et al., New York City, United States. In Genes Dev, Dec 2015
Mammalian cells possess two amino acid-sensing kinases: general control nonderepressible 2 (GCN2) and mechanistic target of rapamycin complex 1 (mTORC1).
Borrelidin Induces the Unfolded Protein Response in Oral Cancer Cells and Chop-Dependent Apoptosis.
Fribley et al., Detroit, United States. In Acs Med Chem Lett, Dec 2015
Murine embryonic fibroblasts (MEFs) null for GCN2 and PERK were less able to accumulate UPR markers and were resistant to borrelidin.
Extensive differential protein phosphorylation as intraerythrocytic Plasmodium falciparum schizonts develop into extracellular invasive merozoites.
Holder et al., Paris, France. In Proteomics, Aug 2015
Within the merozoite phosphoprotein interaction network a subnetwork of 119 proteins with potential roles in cellular movement and invasion was identified and suggested that it is coregulated by a further small subnetwork of protein kinase A (PKA), two calcium-dependent protein kinases (CDPKs), a phosphatidyl inositol kinase (PI3K), and a GCN2-like elF2-kinase with a predicted role in translational arrest and associated changes in the ubquitinome.
Roles of the translation initiation factor eIF2α serine 51 phosphorylation in cancer formation and treatment.
Koromilas, Montréal, Canada. In Biochim Biophys Acta, Jul 2015
Induction of eIF2αS51P is mediated by a family of four kinases namely, HRI, PKR, PERK and GCN2, each of which responds to distinct forms of stress.
KRAS Genotype Correlates with Proteasome Inhibitor Ixazomib Activity in Preclinical In Vivo Models of Colon and Non-Small Cell Lung Cancer: Potential Role of Tumor Metabolism.
Amidon et al., Durham, United States. In Plos One, 2014
Depletion of free amino acid pools and activation of GCN2-eIF2α-pathways were observed both in tumor types.
Sensing of amino acids in a dopaminergic circuitry promotes rejection of an incomplete diet in Drosophila.
Léopold et al., Nice, France. In Cell, 2014
We demonstrate that the amino acid sensor GCN2 acts upstream of GABA signaling in DA neurons to promote avoidance of the EAA-deficient diet.
Vaccine activation of the nutrient sensor GCN2 in dendritic cells enhances antigen presentation.
Pulendran et al., Atlanta, United States. In Science, 2014
Recent studies using systems biology approaches in humans have revealed that YF-17D-induced early expression of general control nonderepressible 2 kinase (GCN2) in the blood strongly correlates with the magnitude of the later CD8(+) T cell response.
EIF2AK4 mutations cause pulmonary veno-occlusive disease, a recessive form of pulmonary hypertension.
Soubrier et al., Paris, France. In Nat Genet, 2014
Using whole-exome sequencing, we detected recessive mutations in EIF2AK4 (also called GCN2) that cosegregated with PVOD in all 13 families studied.
GCN2, an old dog with new tricks.
Boye et al., Oslo, Norway. In Biochem Soc Trans, 2013
Gcn2 was first described in budding yeast as a serine/threonine protein kinase involved in the response to amino acid starvation and this is its best characterized role to date.
Small molecule modulators of eukaryotic initiation factor 2α kinases, the key regulators of protein synthesis.
Pal et al., Pune, India. In Biochimie, 2013
In mammalian cells, there are four eIF-2α kinases, namely HRI (Heme-Regulated Inhibitor), PKR (RNA-dependent Protein Kinase), PERK (PKR-like ER Kinase) and GCN2 (General Control Non-derepressible 2).
Nutrient sensing and metabolic stress pathways in innate immunity.
Girardin et al., Toronto, Canada. In Cell Microbiol, 2013
Cells monitor nutrient availability through several highly conserved pathways that include the mTOR signalling axis regulated by AKT/PI3K, HIF and AMPK, as well as the GCN2/eIF2α integrated stress response pathway that provides cellular adaptation to amino acid starvation.
AMPK and GCN2-ATF4 signal the repression of mitochondria in colon cancer cells.
Cuezva et al., Madrid, Spain. In Biochem J, 2012
Changes in translational control of mitochondrial proteins are signaled by the activation of AMPK (AMP-activated protein kinase) and GCN2, leading also to the activation of autophagy.
Endoplasmic reticulum stress in retinal vascular degeneration: protective role of resveratrol.
Zheng et al., Wuhan, China. In Invest Ophthalmol Vis Sci, 2012
High dosage of resveratrol pretreatment inhibited the injury-induced up-regulation of eIF2alpha-CHOP and IRE1alpha-XBP1 pathways.
Pkh1 interacts with and phosphorylates components of the yeast Gcn2/eIF2α system.
Van Zeebroeck et al., Leuven, Belgium. In Biochem Biophys Res Commun, 2012
the interaction between Pkh1 and Gcn2 was confirmed by co-immunoprecipitation and Pkh1 was shonwn to phosphorylate Gcn2 in vitro.
Increased susceptibility to DNA virus infection in mice with a GCN2 mutation.
Beutler et al., Los Angeles, United States. In J Virol, 2012
describe the recessive, loss-of-function mutation atchoum (atc) in Eif2ak4, encoding GCN2, which increased susceptibility to infection by the double-stranded DNA viruses mouse cytomegalovirus (MCMV) and human adenovirus
Surgical stress resistance induced by single amino acid deprivation requires Gcn2 in mice.
Mitchell et al., Boston, United States. In Sci Transl Med, 2012
Both dietary and pharmacological interventions required the amino acid sensor and eIF2alpha kinase Gcn2, implicating the amino acid starvation response and translational control in stress protection.
The metabolic sensor GCN2 branches out.
Towle, Minneapolis, United States. In Cell Metab, 2007
GCN2 is a sensor of amino acid deprivation that triggers a repression of global protein synthesis while simultaneously inducing translation of specific proteins.
The GCN2 eIF2alpha kinase regulates fatty-acid homeostasis in the liver during deprivation of an essential amino acid.
Cavener et al., United States. In Cell Metab, 2007
This study identifies a novel function of GCN2 in regulating lipid metabolism during leucine deprivation in addition to regulating amino acid metabolism.
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