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October 3, 2025Science

GCN1 couples GCN2 to ribosomal state to initiate amino acid response pathway signaling

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Authors

CZChangqian ZhouMZMiao ZhangJMJ. Murray

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Overview

In vitro analysis reveals GCN1 initiates GCN2 signaling via ribosomal collision, suggesting a new mechanism in amino acid response.

Key Points

  • GCN2 activation requires GCN1 to recruit it to ribosomes, enhancing the signaling pathway during nutrient deprivation.
  • Key evidence indicates that GCN2 forms stable associations with collided ribosomes, facilitating its activation in response to amino acid stress.
  • Using in vitro translation, this analysis reconstitutes the effects of translational stressors on GCN2 signaling activation dynamics.
  • Understanding these molecular interactions may inform metabolic regulation strategies under nutrient scarcity.

Cite This Study

Zhou et al. (2025) studied this question.

synapsesocial.com/papers/68e02f46f0e39f13e7fa2df3https://doi.org/10.1126/science.ads8728
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1GCN2 in Proteostasis: Structural Logic, Signalling Networks, and Disease2026
  2. 2Abstract 1691 Differential Response of GCN2 eIF2 Kinase to Specific Amino Acid Limitations in Prostate Cancer2024
  3. 3An integrated stress response-independent role of GCN2 prevents excessive ribosome biogenesis and mRNA translation2024
  4. 4Exploring the multifaceted role of GCN1: Implications in cellular responses and disease pathogenesis2024 · 7 citations
  5. 5Gcn2 structurally mimics and functionally repurposes the HisRS enzyme for the integrated stress response2024 · 8 citations