Results 121 to 130 of about 6,913 (153)

Activation of GCN2 by the ribosomal P-stalk [PDF]

Proceedings of the National Academy of Sciences of the United States of America, 2019
Significance General control nonderepressible 2 (GCN2) phosphorylates eIF2α, regulating translation in response to nutritional stress. Here, we show that although tRNA stimulates purified, recombinant human GCN2 in vitro, mammalian ribosomes are even more potent GCN2 activators.
Glenn R Masson, Sichen Shao, Stephen H Mclaughlin   +2 more
exaly   +4 more sources

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 (
Millie M Georgiadis, Kirk A Staschke, Ronald C Wek   +2 more
exaly   +4 more sources

Multiple Roles of the Stress Sensor GCN2 in Immune Cells

International Journal of Molecular Sciences, 2023
The serine/threonine-protein kinase general control nonderepressible 2 (GCN2) is a well-known stress sensor that responds to amino acid starvation and other stresses, making it critical to the maintenance of cellular and organismal homeostasis.
Han Guo, Yangxiao Hou, Tong Lei
exaly   +3 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.
BEATRIZ A Castilho, Richard Cardoso da Silva, Rashmi Ramesh   +2 more
exaly   +3 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.
Jyothsna Visweswaraiah, BEATRIZ A Castilho, Terri Goss Kinzy   +2 more
exaly   +5 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

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 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 kinase activation by ATP-competitive kinase inhibitors

Nature Chemical Biology, 2021
Small-molecule kinase inhibitors represent a major group of cancer therapeutics, but tumor responses are often incomplete. To identify pathways that modulate kinase inhibitor response, we conducted a genome-wide knockout (KO) screen in glioblastoma cells treated with the pan-ErbB inhibitor neratinib.
Colin P. Tang, Owen Clark, John R. Ferrarone, Carl Campos, Alshad S. Lalani, John D. Chodera, Andrew M. Intlekofer, Olivier Elemento, Ingo K. Mellinghoff   +8 more
openaire   +2 more sources