Results 131 to 140 of about 7,295 (170)

Activation of Gcn2 by small molecules designed to be inhibitors

Journal of Biological Chemistry, 2023
The integrated stress response (ISR) is an important mechanism by which cells confer protection against environmental stresses. Central to the ISR is a collection of related protein kinases that monitor stress conditions, such as Gcn2 (EIF2AK4) that recognizes nutrient limitations, inducing phosphorylation of eukaryotic translation initiation factor 2 (
Kirk Alan Staschke, Ronald C. Wek, Millie M. Georgiadis   +2 more
exaly   +4 more sources

Keeping the eIF2 alpha kinase Gcn2 in check

Biochimica Et Biophysica Acta - Molecular Cell Research, 2014
The protein kinase Gcn2 is present in virtually all eukaryotes and is of increasing interest due to its involvement in a large array of crucial biological processes. Some of these are universally conserved from yeast to humans, such as coping with nutrient starvation and oxidative stress. In mammals, Gcn2 is important for e.g.
Evelyn Sattlegger, Richard C Silva, Rashmi Ramesh   +2 more
exaly   +3 more sources

Association of GCN1–GCN20 regulatory complex with the N‐terminus of eIF2α kinase GCN2 is required for GCN2 activation [PDF]

EMBO Journal, 2000
Stimulation of GCN4 mRNA translation due to phosphorylation of the alpha-subunit of initiation factor 2 (eIF2) by its specific kinase, GCN2, requires binding of uncharged tRNA to a histidyl-tRNA synthetase (HisRS)-like domain in GCN2. GCN2 function in vivo also requires GCN1 and GCN20, but it was unknown whether these latter proteins act directly to ...
Jinsheng Dong
exaly   +4 more sources

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A new role of GCN2 in the nucleolus

Biochemical and Biophysical Research Communications, 2017
General control nonderepressible 2 (GCN2) is activated by the accumulation of uncharged tRNA in response to amino acid shortage and regulates amino acid starvation response in the cytosol. Here we report the nucleolar localization of GCN2 and the association between GCN2 and small RNA transcripts.
Akito Nakamura, Hiromichi Kimura
openaire   +2 more sources

Evidence That Eukaryotic Translation Elongation Factor 1A (eEF1A) Binds the Gcn2 Protein C Terminus and Inhibits Gcn2 Activity *♦ [PDF]

Journal of Biological Chemistry, 2011
The eukaryotic elongation factor 1A (eEF1A) delivers aminoacyl-tRNAs to the ribosomal A-site during protein synthesis. To ensure a continuous supply of amino acids, cells harbor the kinase Gcn2 and its effector protein Gcn1. The ultimate signal for amino acid shortage is uncharged tRNAs.
Evelyn Sattlegger, Terri Goss Kinzy
exaly   +5 more sources

GCN2, an old dog with new tricks

Biochemical Society Transactions, 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. Recent work has revealed new and exciting roles for Gcn2, which affect many aspects of cellular physiology in response to a number of stresses in addition to starvation ...
Beáta, Grallert, Erik, Boye
openaire   +2 more sources

GCN2 monitors mRNA translation termination

Molecular Cell
Controlling mRNA translation is critical for proper protein production. Although translation initiation and elongation regulations are becoming increasingly clear, whether and how translation termination is monitored remains poorly understood. Using an acute protein degradation system coupled with phenotypic rescue via ectopic expression, here we show ...
Kailey Worner, Katharine R. Maschhoff, Gabrielle M. Schuh, Wenqian Hu   +3 more
openaire   +2 more sources

GCN2 signalling is dysregulated in pulmonary fibrosis

13.01 - Pulmonary hypertension, 2020
Background: GCN2, a major stress regulator, was recently implicated in pulmonary veno-occlusive disease (Eyries M, et al. Nat Genet 2014 and Perros F, et al. Circulation 2015). This study aims to explore the involvement of the GCN2/eIF2α signalling pathway in the development of pulmonary hypertension (PH) during idiopathic pulmonary fibrosis (IPF), in
D Santos Ribeiro, M Lecocq, M De Beukelaer, C Bouzin, S Verleden, Y Yakoub, R Quarck, F Huaux, H Karmouty-Quintana, S Horman, F Perros, L Godinas, C Pilette   +12 more
openaire   +1 more source

GCN2 in Cancer: Molecular Mechanisms to Therapeutic Potential

Current Cancer Drug Targets
Virtually every mammalian cell contains the cytoplasmic protein kinase General Control Non-depressible 2 (GCN2), which allows cells to cope with stresses such as nutrient shortage. While GCN2 is not essential for normal cells, in many cancers GCN2 assumes a pivotal role, becoming indispensable for cell growth ...
Hayley Prescott, Makhdoom Sarwar, Martin Dickens, Evelyn Sattlegger   +3 more
openaire   +2 more sources

GCN2 activation and eIF2α phosphorylation in the maturation of mouse oocytes

Biochemical and Biophysical Research Communications, 2009
GCN2 is one of the four mammalian kinases that phosphorylate the alpha subunit of the translation initiation factor 2 (eIF2alpha) in a variety of stress situations, resulting in protein synthesis inhibition. GCN2 is involved in regulating metabolism, feeding behavior and memory in rodents. We show here that, relative to other cells, the beta isoform of
Viviane S, Alves, Fabiana L, Motta, Martín, Roffé, Arthur, Delamano, João B, Pesquero, Beatriz A, Castilho   +5 more
openaire   +2 more sources