ArticlePLoS genetics2020
Ribosome binding protein GCN1 regulates the cell cycle and cell proliferation and is essential for the embryonic development of mice.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- The endosteal niche regulates breast cancer cell dormancy in bone: identification of new molecular determinants.Bone research · 2026Article
- Saccharomyces cerevisiae as a model for mammalian diseases.FEMS yeast research · 2026Review
- A genetic approach to identify amino acids in human GCN1 required for mediating Gcn2 activation.microPublication biology · 2026Article
- GCN2 in Cancer: Molecular Mechanisms to Therapeutic Potential.Current cancer drug targets · 2026Review
- Expression of IMPACT Curtails Metabolic Plasticity and Augments NK Cell Killing to Abrogate Metastatic Growth.Cancer discovery · 2025Article
- Highly expressed GCN1 is associated with cancer progression and poor prognosis in hepatocellular carcinoma patients.Cancer cell international · 2025Article
- Probiotics under Selective Pressure: Novel Insights and Biosafety Challenge.Archives of Razi Institute · 2024Review
- Transcriptomic Analysis of the Hepatopancreas in the Sex-Related Size Differences ofVeterinary sciences · 2024Article
- A three-dimensional valve-on-chip microphysiological system implicates cell cycle progression, cholesterol metabolism and protein homeostasis in early calcific aortic valve disease progression.Acta biomaterialia · 2024Article
- Evidence that Xrn1 is in complex with Gcn1, and is required for full levels of eIF2α phosphorylation.The Biochemical journal · 2024Article
- Emerging Role of GCN1 in Disease and Homeostasis.International journal of molecular sciences · 2024Review
- Is there a localized role for translational quality control?RNA (New York, N.Y.) · 2023Article
- The orally bioavailable GSPT1/2 degrader SJ6986 exhibits in vivo efficacy in acute lymphoblastic leukemia.Blood · 2023Article
- Article
- Multiple Roles of the Stress Sensor GCN2 in Immune Cells.International journal of molecular sciences · 2023Review
- Article
- General control nonderepressible 1 interacts with cationic amino acid transporter 1 and affects Aedes aegypti fecundity.Parasites & vectors · 2022Article
- GCN2: roles in tumour development and progression.Biochemical Society transactions · 2022Review
- MIRO2 Regulates Prostate Cancer Cell Growth via GCN1-Dependent Stress Signaling.Molecular cancer research : MCR · 2022Article
- Inducible SystemicInternational journal of molecular sciences · 2022Article
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amino acids exert many biological functions, serving as allosteric regulators and neurotransmitters, as constituents in proteins and as nutrients. GCN2-mediated phosphorylation of eukaryotic initiation factor 2 alpha (elF2α) restores homeostasis in response to amino acid starvation (AAS) through the inhibition of the general translation and upregulation of amino acid biosynthetic enzymes and transporters by activating the translation of Gcn4 and ATF4 in yeast and mammals, respectively. GCN1 is a GCN2-binding protein that possesses an RWD binding domain (RWDBD) in its C-terminus. In yeast, Gcn1 is essential for Gcn2 activation by AAS; however, the roles of GCN1 in mammals need to be established. Here, we revealed a novel role of GCN1 that does not depend on AAS by generating two Gcn1 mutant mouse lines: Gcn1-knockout mice (Gcn1 KO mice (Gcn1-/-)) and RWDBD-deleted mutant mice (Gcn1ΔRWDBD mice). Both mutant mice showed growth retardation, which was not observed in the Gcn2 KO mice, such that the Gcn1 KO mice died at the intermediate stage of embryonic development because of severe growth retardation, while the Gcn1ΔRWDBD embryos showed mild growth retardation and died soon after birth, most likely due to respiratory failure. Extension of pregnancy by 24 h through the administration of progesterone to the pregnant mothers rescued the expression of differentiation markers in the lungs and prevented lethality of the Gcn1ΔRWDBD pups, indicating that perinatal lethality of the Gcn1ΔRWDBD embryos was due to simple growth retardation. Similar to the yeast Gcn2/Gcn1 system, AAS- or UV irradiation-induced elF2α phosphorylation was diminished in the Gcn1ΔRWDBD mouse embryonic fibroblasts (MEFs), suggesting that GCN1 RWDBD is responsible for GCN2 activity. In addition, we found reduced cell proliferation and G2/M arrest accompanying a decrease in Cdk1 and Cyclin B1 in the Gcn1ΔRWDBD MEFs. Our results demonstrated, for the first time, that GCN1 is essential for both GCN2-dependent stress response and GCN2-independent cell cycle regulation.
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