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   Articles with "gcn2" as a keyword



GCN2 is essential for CD8+ T cell survival and function in murine models of malignant glioma

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recommendations! Published in 2019 at "Cancer Immunology, Immunotherapy"

DOI: 10.1007/s00262-019-02441-6

Abstract: Amino acid deprivation is a strategy that malignancies utilize to blunt anti-tumor T-cell immune responses. It has been proposed that amino acid insufficiency in T-cells is detected by GCN2 kinase, which through phosphorylation of EIF2α,… read more here.

Keywords: cd8 cell; cd8; gcn2; cd8 cells ... See more keywords

Discovery of HC-7366: An Orally Bioavailable and Efficacious GCN2 Kinase Activator.

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recommendations! Published in 2024 at "Journal of medicinal chemistry"

DOI: 10.1021/acs.jmedchem.3c02384

Abstract: A series of activators of GCN2 (general control nonderepressible 2) kinase have been developed, leading to HC-7366, which has entered the clinic as an antitumor therapy. Optimization resulted in improved permeability compared to that of… read more here.

Keywords: orally bioavailable; 7366 orally; bioavailable efficacious; gcn2 ... See more keywords

RAF inhibitors activate the integrated stress response by direct activation of GCN2

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recommendations! Published in 2025 at "Nature Communications"

DOI: 10.1038/s41467-025-65376-w

Abstract: Paradoxical 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… read more here.

Keywords: rafi; response; activation; gcn2 ... See more keywords

GCN2 phosphorylates HIV-1 integrase and decreases HIV-1 replication by limiting viral integration

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recommendations! Published in 2017 at "Scientific Reports"

DOI: 10.1038/s41598-017-02276-0

Abstract: GCN2 is a serine/threonine kinase involved in cellular stress response related to amino acid starvation. Previously, we showed that GCN2 interacts with HIV-1 integrase and is activated during HIV-1 infection. Herein, we identified HIV-1 integrase… read more here.

Keywords: integrase; integration; gcn2; gcn2 phosphorylates ... See more keywords

Towards a model of GCN2 activation

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recommendations! Published in 2019 at "Biochemical Society Transactions"

DOI: 10.1042/bst20190331

Abstract: Cells must be able to sense and adapt to their surroundings to thrive in a dynamic environment. Key to adapting to a low nutrient environment is the Integrated Stress Response (ISR), a short-lived pathway that… read more here.

Keywords: towards model; activation; gcn2 activation; gcn2 ... See more keywords

GCN2: roles in tumour development and progression

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recommendations! Published in 2022 at "Biochemical Society Transactions"

DOI: 10.1042/bst20211252

Abstract: GCN2 (general control nonderepessible 2) is an eIF2α kinase responsible for entirely rewiring the metabolism of cells when they are put under amino acid starvation stress. Recently, there has been renewed interest in GCN2 as… read more here.

Keywords: gcn2; development; roles tumour; gcn2 roles ... See more keywords

Activation of GCN2 by the ribosomal P-stalk

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recommendations! Published in 2019 at "Proceedings of the National Academy of Sciences of the United States of America"

DOI: 10.1073/pnas.1813352116

Abstract: 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… read more here.

Keywords: ribosomal stalk; gcn2; gcn2 activation; stalk ... See more keywords

The amino acid sensor GCN2 controls red blood cell clearance and iron metabolism through regulation of liver macrophages

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recommendations! Published in 2022 at "Proceedings of the National Academy of Sciences of the United States of America"

DOI: 10.1073/pnas.2121251119

Abstract: Significance In this study, we define a regulatory pathway controlling tissue-resident macrophages during stress through the translational control of a subset of messenger RNAs (mRNAs) and transcriptional reprogramming. Our data reveal that the GCN2-eIF2α pathway… read more here.

Keywords: clearance; gcn2; red blood; liver macrophages ... See more keywords

Differential requirements for P stalk components in activating yeast protein kinase Gcn2 by stalled ribosomes during stress.

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recommendations! Published in 2023 at "Proceedings of the National Academy of Sciences of the United States of America"

DOI: 10.1073/pnas.2300521120

Abstract: The General Amino Acid Control is a conserved response to amino acid starvation involving activation of protein kinase Gcn2, which phosphorylates eukaryotic initiation factor 2 (eIF2α) with attendant inhibition of global protein synthesis and increased… read more here.

Keywords: gcn2; protein kinase; requirements stalk; kinase gcn2 ... See more keywords

Structure of a Gcn2 dimer in complex with the large 60S ribosomal subunit

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recommendations! Published in 2025 at "Proceedings of the National Academy of Sciences of the United States of America"

DOI: 10.1073/pnas.2415807122

Abstract: Significance Gcn2 is a critically important protein kinase of the integrated stress response (ISR) pathway and is conserved from yeast to humans. Although Gcn2 has long been known to interact with 60S subunits, structural insight… read more here.

Keywords: structure gcn2; subunit; gcn2 dimer; gcn2 ... See more keywords

Autophagy contributes to sulfonylurea herbicide tolerance via GCN2-independent regulation of amino acid homeostasis

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recommendations! Published in 2018 at "Autophagy"

DOI: 10.1080/15548627.2017.1407888

Abstract: ABSTRACT Sulfonylurea (SU) herbicides inhibit branched-chain amino acid (BCAA) biosynthesis by targeting acetolactate synthase. Plants have evolved target-site resistance and metabolic tolerance to SU herbicides; the GCN2 (general control non-repressible 2) pathway is also involved… read more here.

Keywords: amino acid; tolerance; gcn2; autophagy ... See more keywords