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Cited by 16RNA and protein synthesis mechanismsPI3K/AKT/mTOR signaling in cancerGenetics, Aging, and Longevity in Model Organisms

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Emerging Role of GCN1 in Disease and Homeostasis

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Tatara, Yota, Kasai, Shuya, Kokubu, Daichi, Tsujita, Tadayuki, Mimura, Junsei, Itoh, Ken·2024·International Journal of Molecular Sciences
DOI 10.3390/ijms25052998PMC PMC10931611

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Abstract

GCN1 is recognized as a factor that is essential for the activation of GCN2, which is a sensor of amino acid starvation. This function is evolutionarily conserved from yeast to higher eukaryotes. However, recent studies have revealed non-canonical functions of GCN1 that are independent of GCN2, such as its participation in cell proliferation, apoptosis, and the immune response, beyond the borders of species. Although it is known that GCN1 and GCN2 interact with ribosomes to accomplish amino acid starvation sensing, recent studies have reported that GCN1 binds to disomes (i.e., ribosomes that collide each other), thereby regulating both the co-translational quality control and stress response. We propose that GCN1 regulates ribosome-mediated signaling by dynamically changing its partners among RWD domain-possessing proteins via unknown mechanisms. We recently demonstrated that GCN1 is essential for cell proliferation and whole-body energy regulation in mice. However, the manner in which ribosome-initiated signaling via GCN1 is related to various physiological functions warrants clarification. GCN1-mediated mechanisms and its interaction with other quality control and stress response signals should be important for proteostasis during aging and neurodegenerative diseases, and may be targeted for drug development.

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Metadata

Authors
Tatara, Y., Kasai, S., Kokubu, D., Tsujita, T., Mimura, J., & Itoh, K.
Affiliations
  • Hirosaki University (JP)
  • Saga University (JP)
Corresponding author
Itoh, Ken
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2024-03-05
Volume
25
Issue
5
Pages
2998
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms25052998
PMC
PMC10931611
OpenAlex
W4392469865
Cited by
16
References
5
Citations by year
2026: 7 · 2025: 6 · 2024: 3
FWCI
0.65
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • Preprints.org (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • JSPS KAKENHI (22H03515, 26111010)
  • Grant-in-Aid (22H03515, 26111010)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords
GCN1, GCN2, ribosome collisions, cell proliferation, apoptosis, immune response, energy homeostasis, proteostasis, aging, neurodegenerative diseases, stress response
MeSH terms
Amino Acids, Animals, Homeostasis, Humans, Peptide Elongation Factors, Saccharomyces cerevisiae, Trans-Activators, RNA-Binding Proteins, Protein Serine-Threonine Kinases, Saccharomyces cerevisiae Proteins, Mice

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