GCN2 in proteostasis: structural logic, signalling networks and disease - PubMed
12 hours ago
- #proteostasis
- #integrated stress response
- #GCN2
- Proteostasis is the balance of protein synthesis, folding, and degradation essential for cellular health.
- GCN2 is a central kinase in the integrated stress response (ISR), sensing amino acid deprivation and ribosomal stress.
- Activated GCN2 phosphorylates eIF2α, reducing global translation but enhancing synthesis of stress-responsive transcription factors ATF4 and CHOP.
- ATF4 regulates processes like amino acid metabolism, redox homeostasis, autophagy, and proteasomal degradation to restore proteostasis.
- GCN2 interacts with other networks, including mTORC1, to promote autophagy and stress granule formation.
- Dysregulated GCN2 is linked to diseases such as neurodegeneration, cancer, and pulmonary vascular disease.
- GCN2's role in nutrient sensing and metabolic adaptation makes it a potential therapeutic target for protein misfolding diseases.