Multiple Roles of the Stress Sensor GCN2 in Immune Cells

Author:

Zhao Chenxu12,Guo Han12ORCID,Hou Yangxiao12,Lei Tong12,Wei Dong12,Zhao Yong123ORCID

Affiliation:

1. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China

2. University of Chinese Academy of Sciences, Beijing 100049, China

3. Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China

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.

Funder

National Natural Science Foundation

the Knowledge Innovation Program of the Chinese Academy of Sciences

the National Key Research and Development Program of China

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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