Multiple Roles of the Stress Sensor GCN2 in Immune Cells

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. More than 20 years of research has revealed the molecul...

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Published inInternational journal of molecular sciences Vol. 24; no. 5; p. 4285
Main Authors Zhao, Chenxu, Guo, Han, Hou, Yangxiao, Lei, Tong, Wei, Dong, Zhao, Yong
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 21.02.2023
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Abstract 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. More than 20 years of research has revealed the molecular structure/complex, inducers/regulators, intracellular signaling pathways and bio-functions of GCN2 in various biological processes, across an organism’s lifespan, and in many diseases. Accumulated studies have demonstrated that the GCN2 kinase is also closely involved in the immune system and in various immune-related diseases, such as GCN2 acts as an important regulatory molecule to control macrophage functional polarization and CD4+ T cell subset differentiation. Herein, we comprehensively summarize the biological functions of GCN2 and discuss its roles in the immune system, including innate and adaptive immune cells. We also discuss the antagonism of GCN2 and mTOR pathways in immune cells. A better understanding of GCN2′s functions and signaling pathways in the immune system under physiological, stressful, and pathological situations will be beneficial to the development of potential therapies for many immune-relevant diseases.
AbstractList 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. More than 20 years of research has revealed the molecular structure/complex, inducers/regulators, intracellular signaling pathways and bio-functions of GCN2 in various biological processes, across an organism's lifespan, and in many diseases. Accumulated studies have demonstrated that the GCN2 kinase is also closely involved in the immune system and in various immune-related diseases, such as GCN2 acts as an important regulatory molecule to control macrophage functional polarization and CD4[sup.+] T cell subset differentiation. Herein, we comprehensively summarize the biological functions of GCN2 and discuss its roles in the immune system, including innate and adaptive immune cells. We also discuss the antagonism of GCN2 and mTOR pathways in immune cells. A better understanding of GCN2′s functions and signaling pathways in the immune system under physiological, stressful, and pathological situations will be beneficial to the development of potential therapies for many immune-relevant diseases.
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. More than 20 years of research has revealed the molecular structure/complex, inducers/regulators, intracellular signaling pathways and bio-functions of GCN2 in various biological processes, across an organism’s lifespan, and in many diseases. Accumulated studies have demonstrated that the GCN2 kinase is also closely involved in the immune system and in various immune-related diseases, such as GCN2 acts as an important regulatory molecule to control macrophage functional polarization and CD4+ T cell subset differentiation. Herein, we comprehensively summarize the biological functions of GCN2 and discuss its roles in the immune system, including innate and adaptive immune cells. We also discuss the antagonism of GCN2 and mTOR pathways in immune cells. A better understanding of GCN2′s functions and signaling pathways in the immune system under physiological, stressful, and pathological situations will be beneficial to the development of potential therapies for many immune-relevant diseases.
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. More than 20 years of research has revealed the molecular structure/complex, inducers/regulators, intracellular signaling pathways and bio-functions of GCN2 in various biological processes, across an organism's lifespan, and in many diseases. Accumulated studies have demonstrated that the GCN2 kinase is also closely involved in the immune system and in various immune-related diseases, such as GCN2 acts as an important regulatory molecule to control macrophage functional polarization and CD4+ T cell subset differentiation. Herein, we comprehensively summarize the biological functions of GCN2 and discuss its roles in the immune system, including innate and adaptive immune cells. We also discuss the antagonism of GCN2 and mTOR pathways in immune cells. A better understanding of GCN2's functions and signaling pathways in the immune system under physiological, stressful, and pathological situations will be beneficial to the development of potential therapies for many immune-relevant diseases.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. More than 20 years of research has revealed the molecular structure/complex, inducers/regulators, intracellular signaling pathways and bio-functions of GCN2 in various biological processes, across an organism's lifespan, and in many diseases. Accumulated studies have demonstrated that the GCN2 kinase is also closely involved in the immune system and in various immune-related diseases, such as GCN2 acts as an important regulatory molecule to control macrophage functional polarization and CD4+ T cell subset differentiation. Herein, we comprehensively summarize the biological functions of GCN2 and discuss its roles in the immune system, including innate and adaptive immune cells. We also discuss the antagonism of GCN2 and mTOR pathways in immune cells. A better understanding of GCN2's functions and signaling pathways in the immune system under physiological, stressful, and pathological situations will be beneficial to the development of potential therapies for many immune-relevant diseases.
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. More than 20 years of research has revealed the molecular structure/complex, inducers/regulators, intracellular signaling pathways and bio-functions of GCN2 in various biological processes, across an organism’s lifespan, and in many diseases. Accumulated studies have demonstrated that the GCN2 kinase is also closely involved in the immune system and in various immune-related diseases, such as GCN2 acts as an important regulatory molecule to control macrophage functional polarization and CD4 + T cell subset differentiation. Herein, we comprehensively summarize the biological functions of GCN2 and discuss its roles in the immune system, including innate and adaptive immune cells. We also discuss the antagonism of GCN2 and mTOR pathways in immune cells. A better understanding of GCN2′s functions and signaling pathways in the immune system under physiological, stressful, and pathological situations will be beneficial to the development of potential therapies for many immune-relevant diseases.
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. More than 20 years of research has revealed the molecular structure/complex, inducers/regulators, intracellular signaling pathways and bio-functions of GCN2 in various biological processes, across an organism's lifespan, and in many diseases. Accumulated studies have demonstrated that the GCN2 kinase is also closely involved in the immune system and in various immune-related diseases, such as GCN2 acts as an important regulatory molecule to control macrophage functional polarization and CD4 T cell subset differentiation. Herein, we comprehensively summarize the biological functions of GCN2 and discuss its roles in the immune system, including innate and adaptive immune cells. We also discuss the antagonism of GCN2 and mTOR pathways in immune cells. A better understanding of GCN2's functions and signaling pathways in the immune system under physiological, stressful, and pathological situations will be beneficial to the development of potential therapies for many immune-relevant diseases.
Audience Academic
Author Zhao, Yong
Guo, Han
Hou, Yangxiao
Wei, Dong
Lei, Tong
Zhao, Chenxu
AuthorAffiliation 1 State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
3 Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China
2 University of Chinese Academy of Sciences, Beijing 100049, China
AuthorAffiliation_xml – name: 1 State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
– name: 2 University of Chinese Academy of Sciences, Beijing 100049, China
– name: 3 Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China
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  fullname: Zhao, Chenxu
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  givenname: Han
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  fullname: Guo, Han
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  fullname: Hou, Yangxiao
– sequence: 4
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  fullname: Wei, Dong
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  orcidid: 0000-0003-2850-3008
  surname: Zhao
  fullname: Zhao, Yong
BackLink https://www.ncbi.nlm.nih.gov/pubmed/36901714$$D View this record in MEDLINE/PubMed
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Keywords immune system
GCN2
stress
tumor
protein kinase
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Snippet The serine/threonine-protein kinase general control nonderepressible 2 (GCN2) is a well-known stress sensor that responds to amino acid starvation and other...
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SubjectTerms Amino acids
Amino Acids - metabolism
Cell cycle
Endoplasmic reticulum
Genetic translation
Heat shock proteins
Homeostasis
Humans
Kinases
Oxidative stress
Phosphatase
Phosphorylation
Physiological aspects
Protein kinases
Protein Serine-Threonine Kinases - metabolism
Protein synthesis
Review
Roles
Signal Transduction
Stress, Physiological
T cells
T-Lymphocyte Subsets - metabolism
Transfer RNA
Yeast
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Title Multiple Roles of the Stress Sensor GCN2 in Immune Cells
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Volume 24
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