Affinage

GCN1

Stalled ribosome sensor GCN1 · UniProt Q92616

Length
2671 aa
Mass
292.7 kDa
Annotated
2026-06-10
32 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GCN1 is a large EF3-like, HEAT-repeat protein that associates with translating ribosomes and functions as the central activator of the eIF2α kinase GCN2 in the general amino acid control / integrated stress response (PMID:8497269, PMID:9234705). Genetically it acts upstream of GCN3 and is required in vivo for GCN2-mediated eIF2α phosphorylation during amino acid starvation without contributing to GCN2's intrinsic catalytic activity (PMID:8497269, PMID:2249755). GCN1 carries physically separable functional modules: an internal EF3-like/ribosome-binding region that mediates polysome association (in part through contact with the small subunit protein Rps10) and is itself an effector for GCN2 activation, and a C-terminal RWD-binding domain (RWDBD) that binds the N-terminal GI/RWD domain of GCN2, with both modules required for kinase activation (PMID:11101534, PMID:10801780, PMID:11350982, PMID:15722345, PMID:25437641, PMID:36441697). GCN1 partners with the ABC-family protein GCN20, which it tethers to ribosomes, and the GCN1–GCN20 complex couples sensing of uncharged tRNA to GCN2 activation (PMID:7621831, PMID:9234705, PMID:10775272). Cryo-EM and in vitro reconstitution establish GCN1 as a disome (collided-ribosome) sensor whose HEAT repeats bridge a leading and a colliding 80S ribosome and recruit GCN2 to stalled ribosomes in a collision-dependent manner (PMID:33790014, PMID:41037622). Activation through the RWDBD is antagonized by the competing RWD-domain inhibitors Yih1 (yeast) and its mammalian counterpart IMPACT, which displace GCN2 from GCN1 (PMID:15937339, PMID:21239490, PMID:24333428). Beyond GCN2 signaling, GCN1 acts as a collision sensor that engages the E3 ligase RNF14 (with RNF25) to ubiquitinate and degrade stalled elongation factors such as eEF1A and to mark RPS27A/eS31, and it initiates CCR4/NOT-dependent cotranslational mRNA decay limiting readthrough products and shaping elongation at non-optimal codons (PMID:36638793, PMID:37339632). In mammals GCN1 is essential for embryonic development and has a GCN2-independent role in cell-cycle progression, with RWDBD-deleted cells showing G2/M arrest and reduced Cdk1/Cyclin B1 (PMID:32324833).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1990 High

    Placed GCN1 within the general amino acid control pathway, establishing it as an upstream activator acting together with GCN2 and above GCN3 — defining the genetic architecture of the response.

    Evidence Genetic epistasis with suppressor and constitutive alleles in yeast

    PMID:2249755

    Open questions at the time
    • Genetic ordering alone does not define the biochemical mechanism of GCN2 activation
    • No molecular partners identified at this stage
  2. 1993 High

    Showed GCN1 is required in vivo for GCN2-mediated eIF2α phosphorylation but dispensable for intrinsic GCN2 kinase activity, establishing GCN1 as a regulatory activator rather than a catalytic component.

    Evidence gcn1Δ deletion, in vitro kinase assays from extracts, EF3-homology sequence analysis in yeast

    PMID:8497269

    Open questions at the time
    • Did not establish how GCN1 promotes GCN2 activation
    • No direct physical interaction demonstrated
  3. 1997 High

    Localized GCN1 (and GCN20) to ribosomes and the cytoplasm and mapped the GCN20-interacting EF3-like segment, linking GCN2 regulation to the translation apparatus.

    Evidence Polysome fractionation, immunofluorescence, Co-IP and truncation mapping in yeast

    PMID:7621831 PMID:9234705

    Open questions at the time
    • How ribosome association couples to GCN2 activation not yet resolved
    • GCN2-binding region not yet mapped
  4. 2001 High

    Defined the bipartite domain logic — a C-terminal RWDBD that binds the GCN2 GI domain plus a separate ribosome-binding region, both required for kinase activation, and connected the complex to uncharged tRNA sensing.

    Evidence In vitro/in vivo binding, R2259A and F2291L point mutants, dominant-negative competition, tRNA overexpression suppression in yeast

    PMID:10775272 PMID:10801780 PMID:11101534 PMID:11350982

    Open questions at the time
    • Did not show how uncharged tRNA is physically presented to GCN2
    • Structural basis of GCN1–ribosome bridging unknown
  5. 2005 High

    Demonstrated that ribosome binding by GCN1 is necessary for full GCN2 activation and that the EF3-like domain has an effector role beyond mere ribosome tethering, refining the activation mechanism.

    Evidence Point mutations reducing polyribosome association, eIF2α phosphorylation assays, Co-IP in yeast

    PMID:15722345

    Open questions at the time
    • Molecular nature of the EF3-like effector function undefined
    • Direct ribosomal contact sites not yet identified
  6. 2013 High

    Established the competitive-inhibitor logic of GCN2 activation via RWD-domain proteins Yih1 and mammalian IMPACT, which displace GCN2 from the GCN1 RWDBD across multiple stresses and species.

    Evidence Co-IP, mutagenesis, competition assays, cross-species overexpression and eIF2α/ATF4 readouts (yeast, mouse cells)

    PMID:15937339 PMID:21239490 PMID:24333428

    Open questions at the time
    • When and how IMPACT/Yih1 are deployed physiologically not fully defined
    • Quantitative competition dynamics at the ribosome unknown
  7. 2015 Medium

    Identified a direct RNA-independent contact between GCN1 and small-subunit protein Rps10/eS10, providing a physical anchor on the ribosome relevant to GCN2 activation.

    Evidence Two-hybrid, in vitro co-precipitation, rps10 deletion eIF2α phosphorylation in yeast

    PMID:25437641

    Open questions at the time
    • Single lab; binding not validated in a full ribosome structural context at the time
    • Functional contribution relative to other contacts not quantified
  8. 2020 High

    Separated GCN1's GCN2-dependent and GCN2-independent functions in mammals, showing essentiality for embryogenesis and an RWDBD-independent role in cell-cycle progression.

    Evidence GCN1 KO and ΔRWDBD mouse lines, MEF eIF2α phosphorylation, flow cytometry, Cdk1/Cyclin B1 immunoblots

    PMID:32324833

    Open questions at the time
    • Molecular mechanism of the GCN2-independent cell-cycle role unresolved
    • Embryonic lethality cause not mechanistically dissected
  9. 2021 High

    Reframed GCN1 as a disome sensor: cryo-EM showed its HEAT repeats span colliding and leading 80S ribosomes, and functional work showed it suppresses frameshifting at collided ribosomes independently of the ISR.

    Evidence Cryo-EM of GCN1–disome; frameshifting reporters and mbf1/hel2 epistasis in yeast

    PMID:33790014 PMID:34916334

    Open questions at the time
    • How collision geometry triggers GCN2 recruitment not directly tested in the structure
    • Mechanism linking GCN1 to frameshifting suppression undefined
  10. 2023 High

    Expanded GCN1 into a hub for ribosome-collision quality control, coupling collision sensing to RNF14/RNF25-mediated ubiquitination of stalled factors and to CCR4/NOT cotranslational mRNA decay shaping elongation at non-optimal codons.

    Evidence Ternatin-4 chemical genetics, ubiquitin-site proteomics, CRISPR KOs, selective ribosome profiling in worm and mammalian cells

    PMID:36638793 PMID:37339632

    Open questions at the time
    • How GCN1 selects between GCN2 activation, ubiquitination, and decay outcomes unknown
    • Direct biochemical interaction with RNF14/CCR4-NOT machinery not fully reconstituted
  11. 2025 High

    Reconstituted GCN2 activation in vitro to prove that collision sensing by GCN1 is the proximal event recruiting and stabilizing GCN2 on collided ribosomes, and showed circadian control of GCN1–ribosome association.

    Evidence In vitro translation reconstitution and collided-ribosome fractionation; ribosome fractionation with tRNA-synthetase mutant in Neurospora

    PMID:39903114 PMID:41037622

    Open questions at the time
    • Conformational steps from GCN1 recruitment to GCN2 trans-autophosphorylation not fully resolved
    • Physiological inputs gating collision-dependent activation incompletely mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how GCN1 partitions collided ribosomes among distinct downstream fates (GCN2/ISR activation, RNF14-mediated factor degradation, CCR4/NOT decay, frameshift suppression) and how recently reported partners integrate with this decision.
  • Decision logic among competing collision-resolution pathways unknown
  • Functional roles of low-confidence partners (Xrn1, MTHFR, MIRO2, RAB25) at the ribosome not established
  • Structural basis of GCN1's GCN2-independent cell-cycle function unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 3 GO:0060090 molecular adaptor activity 2 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005840 ribosome 4 GO:0005829 cytosol 1
Pathway
R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-1640170 Cell Cycle 1 R-HSA-392499 Metabolism of proteins 1 R-HSA-8953854 Metabolism of RNA 1
Partners
GCN2GCN20GIR2IMPACTMIRO2RNF14RPS10YIH1
Complex memberships
GCN1–GCN20 complexGCN1–disome (collided 80S ribosome) complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 GCN1 is required in vivo for phosphorylation of eIF2α by GCN2 in amino acid-starved yeast cells, but is not required for intrinsic GCN2 kinase activity (cell extracts from gcn1Δ strains had wild-type GCN2 kinase activity). GCN1 encodes a 297 kDa protein with an 88 kDa region similar to translation elongation factor 3 (EF3). Genetic deletion (gcn1Δ), in vitro kinase assay from cell extracts, sequence homology analysis Molecular and cellular biology High 8497269
1995 GCN1 and GCN20 physically interact and form a protein complex required to activate GCN2 kinase function; GCN20 co-immunoprecipitates with GCN1 from cell extracts and the two proteins interact in the yeast two-hybrid system. Co-immunoprecipitation, yeast two-hybrid, genetic deletion analysis The EMBO journal High 7621831
1997 GCN1 and GCN20 co-sediment with polysomes and 80S ribosomes; ribosome association of GCN20 is largely dependent on GCN1. GCN1 localizes to the cytoplasm with no association with plasma or vacuolar membranes. The N-terminal 15–25% of GCN20 (not the ABC domains) is required for regulatory function and interacts with an internal EF3-like segment of GCN1. ABC domains of GCN20 are dispensable for GCN1 complex formation and GCN2 stimulation. Polysome sedimentation/fractionation, indirect immunofluorescence, deletion/truncation analysis, co-immunoprecipitation Molecular and cellular biology High 9234705
1990 Genetic epistasis places GCN1 and GCN2 upstream of GCN3 in the general amino acid control pathway: constitutively active gcn3c alleles derepress GCN4 in the absence of GCN1 and GCN2, while constitutively derepressing GCN2 alleles require GCN3 for their phenotype. Genetic epistasis analysis (double mutants, suppressor alleles) Genetics High 2249755
2000 The GCN1–GCN20 complex physically interacts with GCN2 via the N-terminus of GCN2; this interaction is required for GCN2 activation by uncharged tRNA. Overexpression of N-terminal GCN2 segments competitively displaced GCN1 from native GCN2. The requirement for GCN1 was reduced by overexpressing tRNA(His), linking GCN1 function to uncharged tRNA sensing. Co-immunoprecipitation, dominant-negative overexpression, genetic suppression, tRNA overexpression The EMBO journal High 10775272
2000 A C-terminal segment of GCN1 (residues 2052–2428) is necessary and sufficient for binding GCN2 in vivo and in vitro; Arg2259 in this segment is essential for GCN2 binding and GCN1 regulatory function. Separate ribosome-binding and GCN2-binding domains of GCN1 are both required for GCN2 activation in amino acid-starved cells. In vitro binding assay, in vivo co-immunoprecipitation, site-directed mutagenesis (R2259A), dominant-negative overexpression, paromomycin sensitivity assay The EMBO journal High 11101534
2000 GCN2 interacts with GCN1 via a GI (GCN2 and IMPACT) domain at the N-terminus of GCN2; mutations in conserved residues of the GI domain abolish GCN1 binding and abrogate the general amino acid control response. Yeast two-hybrid, deletion/mutagenesis analysis, functional growth assays The Journal of biological chemistry Medium 10801780
2001 A C-terminal segment of GCN1 is sufficient to bind the GI domain of GCN2; the gcn1-F2291L mutation abolishes GCN1–GCN2 interaction and impairs eIF2α phosphorylation, demonstrating that GCN1–GCN2 physical interaction is required for GCN2 kinase activation in vivo. Dual bait two-hybrid, site-directed mutagenesis, eIF2α phosphorylation assay in vivo The Journal of biological chemistry Medium 11350982
2005 Ribosome (polyribosome) binding by GCN1 is required for full activation of GCN2. Point mutations in two conserved, non-contiguous segments of GCN1 reduced polyribosome association without affecting GCN1 expression or GCN20 interaction, and decreased eIF2α phosphorylation. The EF3-like domain of GCN1 has an effector function in GCN2 activation beyond ribosome binding. Polysome sedimentation, site-directed mutagenesis, eIF2α phosphorylation assay, co-immunoprecipitation The Journal of biological chemistry High 15722345
2005 Mouse IMPACT protein binds to the C-terminal GCN1 segment (RWDBD) required for GCN2 interaction, competes with GCN2 for GCN1 binding, and inhibits eIF2α phosphorylation by GCN2 under leucine starvation. IMPACT is the functional mammalian counterpart of yeast Yih1. Co-immunoprecipitation (IMPACT with native mouse GCN1), in vivo overexpression in yeast and mouse embryonic fibroblasts, eIF2α phosphorylation assay, ATF4/CHOP reporter readout The Journal of biological chemistry High 15937339
2009 Gir2 (a GI-domain-containing protein) interacts with GCN1 through its GI domain and co-fractionates with polyribosomes in a partially GCN1-dependent manner; Rbg2 and Gir2 associate with ribosomes. Yeast two-hybrid, polysome fractionation, overexpression growth assays Eukaryotic cell Medium 19448108
2011 Yih1 binds GCN1 via its RWD domain (residues 1–132); residues Asp-102 and Glu-106 in helix 3 of the RWD are essential for GCN1 binding and GCN2 inhibition but dispensable for actin binding. Yih1–actin binding is independent of GCN1 and requires residues 68–258. Yih1 competes with GCN2 for GCN1 binding to inhibit GCN2. Co-immunoprecipitation, site-directed mutagenesis, deletion analysis, in vitro binding assays, GCN2 inhibition functional assays The Journal of biological chemistry High 21239490
2013 Mammalian IMPACT prevents GCN1 association with GCN2 and promotes dissolution of the GCN2–GCN1 complex, thereby inhibiting GCN2 activation under amino acid starvation, proteasome inhibition, UV irradiation, and glucose starvation in mammalian cells. IMPACT overexpression in yeast phenocopies YIH1 overexpression under all GCN1/GCN2-dependent stress conditions. Co-immunoprecipitation (GCN2–GCN1 complex), eIF2α phosphorylation assay, overexpression in yeast and mammalian cells, growth assays under multiple stress conditions Biochemical and biophysical research communications Medium 24333428
2014 C. elegans GCN-1 and ABCF-3 physically interact in vivo and are required for the basal level of eIF2α phosphorylation; they promote apoptosis of somatic and irradiated germ cells. Yeast homologs of GCN-1 and ABCF-3 (GCN1 and GCN20) can substitute for the worm proteins in promoting somatic cell deaths, indicating functional conservation. Co-immunoprecipitation (in vivo), genetic deletion, eIF2α phosphorylation assay, cross-species complementation PLoS genetics Medium 25101958
2015 GCN1 directly contacts the small ribosomal protein Rps10 (S10) via residues 1060–1777; this interaction is RNA-independent (in vitro co-precipitation). Deletion of rps10A or rps10B reduces eIF2α phosphorylation under starvation, consistent with impaired GCN1-mediated GCN2 activation. Yeast two-hybrid, in vitro co-precipitation, deletion strains with eIF2α phosphorylation assay, genetic interaction (eEF3 overexpression) The Biochemical journal Medium 25437641
2020 In mice, GCN1 is essential for embryonic development (GCN1 KO dies mid-embryogenesis). The RWDBD (C-terminal GCN2-binding domain) of GCN1 is required for amino acid starvation- and UV-induced eIF2α phosphorylation in mouse embryonic fibroblasts. GCN1ΔRWDBD MEFs show reduced cell proliferation and G2/M arrest with decreased Cdk1 and Cyclin B1, indicating a GCN2-independent role in cell cycle regulation. Knockout and RWDBD-deletion mouse lines, eIF2α phosphorylation assay in MEFs, cell cycle analysis (flow cytometry), Western blotting for Cdk1/Cyclin B1 PLoS genetics High 32324833
2021 Cryo-EM structure of yeast GCN1 in complex with stalled and colliding 80S ribosomes (disome): GCN1 HEAT repeats span from the P-stalk region of the colliding ribosome to the P-stalk and A-site region of the lead ribosome. The lead ribosome is non-rotated with peptidyl-tRNA in the A-site, uncharged tRNA in the P-site, eIF5A in E-site, and Rbg2/Gir2 at the A-site factor binding region. The colliding ribosome is rotated with peptidyl-tRNA in hybrid A/P-site and Mbf1 bound on the 40S. Cryo-electron microscopy (cryo-EM) structure determination Proceedings of the National Academy of Sciences of the United States of America High 33790014
2021 GCN1 and GCN20 suppress frameshifting at collided ribosomes (at CGA codon repeats) in yeast; deletion of GCN1 or GCN20 increases frameshifting, and this effect is not primarily mediated through ISR activation. Mbf1 requires either Hel2 or GCN1 to suppress frameshifting with wild-type eEF3. Genetic selection for frameshifting mutants, frameshifting reporter assays, genetic epistasis (double mutants with mbf1, hel2) RNA (New York, N.Y.) Medium 34916334
2022 MIRO2 (mitochondrial Rho GTPase 2) interacts with GCN1 in prostate cancer cells; MIRO2 is required for efficient GCN1-mediated GCN2 kinase signaling and ATF4 induction. A prostate-cancer-associated MIRO2 mutation (159L) increases GCN1 binding. Co-immunoprecipitation, protein network analysis, siRNA knockdown, ATF4/GCN2 phosphorylation assays, prostate cancer xenograft model Molecular cancer research : MCR Medium 34992146
2022 Specific amino acid residues R2289, R2297, and K2301 in the GCN1 RWDBD (in addition to the previously known R2259) are required for GCN2 binding; two helices in GCN1 constitute a GCN2-binding site. Dominant-negative overexpression system, site-directed mutagenesis, eIF2α phosphorylation assay PloS one Medium 36441697
2023 GCN1 acts as a ribosome collision sensor that engages E3 ligase RNF14; this GCN1–RNF14 interaction is essential for ubiquitination and degradation of eEF1A on stalled ribosomes with an occluded A-site (induced by ternatin-4). GCN1 is required for RNF14/RNF25-dependent ubiquitination of eEF1A and ribosomal protein RPS27A/eS31. Chemical-genetic approach (ternatin-4), quantitative proteomics (ubiquitin site mapping), CRISPR knockouts of GCN1/RNF14/RNF25, co-immunoprecipitation Cell High 36638793
2023 GCN1 acts as a ribosome collision sensor that initiates cotranslational mRNA decay via CCR4/NOT to limit accumulation of readthrough proteins. GCN1 also regulates translation dynamics at non-optimal codons enriched in 3' UTRs, transmembrane proteins, and collagens (revealed by selective ribosome profiling). GCN1 dysfunction during aging increasingly perturbs these protein classes. Selective ribosome profiling, GCN1 knockdown/knockout in C. elegans and mammalian cells, proteomics, mRNA decay assays Cell High 37339632
2024 Xrn1 co-precipitates with GCN1 and GCN2, suggesting a trimeric complex; deletion of XRN1 reduces eIF2α phosphorylation under starvation and impairs growth under starvation conditions. Constitutively active GCN2-induced eIF2α hyperphosphorylation is independent of Xrn1, arguing against Xrn1 role in eIF2α dephosphorylation. Co-immunoprecipitation (Xrn1 with GCN1/GCN2), deletion strains, eIF2α phosphorylation assay, growth assays The Biochemical journal Low 38440860
2024 MTHFR (methylenetetrahydrofolate reductase) co-purifies with GCN1 in affinity purification coupled mass spectrometry from 293T cells, and the interaction was confirmed by immunoprecipitation-immunoblotting. Affinity purification–mass spectrometry, co-immunoprecipitation–immunoblotting Biochimie Low 39571719
2025 In vitro translation reconstitution demonstrated that GCN2 activation by amino acid stress requires GCN1 as a di-ribosome (collision) sensor; GCN1 recruits GCN2 to ribosomes in a collision-dependent manner, where GCN2 is activated by key ribosomal interactions and stably associated with collided ribosomes. In vitro translation reconstitution, biochemical fractionation of collided ribosome populations, quantitative proteomics Science (New York, N.Y.) High 41037622
2025 In Neurospora crassa, the circadian clock regulates GCN1 and CPC-3 (GCN2 ortholog) association with ribosomes in a rhythmic manner; these interactions are required for clock-regulated CPC-3 activity. GCN1 interaction with uncharged tRNA (modulated by GCN20) is controlled by the clock and drives rhythmic CPC-3 activation. Ribosome fractionation/sedimentation, temperature-sensitive tRNA synthetase mutant (un-3), genetic deletion of GCN20, eIF2α phosphorylation assay at different circadian times Proceedings of the National Academy of Sciences of the United States of America Medium 39903114
2025 RAB25 interacts with GCN1 in hepatocytes (confirmed by mass spectrometry and co-immunoprecipitation); RAB25 binding to GCN1 inhibits K33-ubiquitination-mediated degradation of GCN1, thereby promoting GCN2 phosphorylation and ATF4-mediated ER stress in alcohol-associated liver disease. Mass spectrometry, co-immunoprecipitation, ubiquitination analysis, GCN1/GCN2 knockdown, in vitro and in vivo ALD models Clinical and molecular hepatology Medium 40916695

Source papers

Stage 0 corpus · 32 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Evidence that GCN1 and GCN20, translational regulators of GCN4, function on elongating ribosomes in activation of eIF2alpha kinase GCN2. Molecular and cellular biology 181 9234705
1995 GCN20, a novel ATP binding cassette protein, and GCN1 reside in a complex that mediates activation of the eIF-2 alpha kinase GCN2 in amino acid-starved cells. The EMBO journal 141 7621831
2021 Structure of Gcn1 bound to stalled and colliding 80S ribosomes. Proceedings of the National Academy of Sciences of the United States of America 127 33790014
2000 Separate domains in GCN1 for binding protein kinase GCN2 and ribosomes are required for GCN2 activation in amino acid-starved cells. The EMBO journal 125 11101534
2000 Association of GCN1-GCN20 regulatory complex with the N-terminus of eIF2alpha kinase GCN2 is required for GCN2 activation. The EMBO journal 121 10775272
1993 GCN1, a translational activator of GCN4 in Saccharomyces cerevisiae, is required for phosphorylation of eukaryotic translation initiation factor 2 by protein kinase GCN2. Molecular and cellular biology 121 8497269
1990 The translational activator GCN3 functions downstream from GCN1 and GCN2 in the regulatory pathway that couples GCN4 expression to amino acid availability in Saccharomyces cerevisiae. Genetics 75 2249755
2005 Polyribosome binding by GCN1 is required for full activation of eukaryotic translation initiation factor 2{alpha} kinase GCN2 during amino acid starvation. The Journal of biological chemistry 74 15722345
2005 IMPACT, a protein preferentially expressed in the mouse brain, binds GCN1 and inhibits GCN2 activation. The Journal of biological chemistry 69 15937339
2023 An E3 ligase network engages GCN1 to promote the degradation of translation factors on stalled ribosomes. Cell 66 36638793
2000 GI domain-mediated association of the eukaryotic initiation factor 2alpha kinase GCN2 with its activator GCN1 is required for general amino acid control in budding yeast. The Journal of biological chemistry 66 10801780
2023 Mechanisms of readthrough mitigation reveal principles of GCN1-mediated translational quality control. Cell 56 37339632
2001 Budding yeast GCN1 binds the GI domain to activate the eIF2alpha kinase GCN2. The Journal of biological chemistry 48 11350982
2011 Gcn1 and actin binding to Yih1: implications for activation of the eIF2 kinase GCN2. The Journal of biological chemistry 33 21239490
2020 Ribosome binding protein GCN1 regulates the cell cycle and cell proliferation and is essential for the embryonic development of mice. PLoS genetics 32 32324833
2013 Evolutionarily conserved IMPACT impairs various stress responses that require GCN1 for activating the eIF2 kinase GCN2. Biochemical and biophysical research communications 30 24333428
2009 Saccharomyces cerevisiae Rbg1 protein and its binding partner Gir2 interact on Polyribosomes with Gcn1. Eukaryotic cell 29 19448108
2015 Hirsutinolide Series Inhibit Stat3 Activity, Alter GCN1, MAP1B, Hsp105, G6PD, Vimentin, TrxR1, and Importin α-2 Expression, and Induce Antitumor Effects against Human Glioma. Journal of medicinal chemistry 24 26331426
2014 The translational regulators GCN-1 and ABCF-3 act together to promote apoptosis in C. elegans. PLoS genetics 23 25101958
2022 MIRO2 Regulates Prostate Cancer Cell Growth via GCN1-Dependent Stress Signaling. Molecular cancer research : MCR 22 34992146
2015 Gcn1 contacts the small ribosomal protein Rps10, which is required for full activation of the protein kinase Gcn2. The Biochemical journal 22 25437641
2021 Frameshifting at collided ribosomes is modulated by elongation factor eEF3 and by integrated stress response regulators Gcn1 and Gcn20. RNA (New York, N.Y.) 15 34916334
2017 Recognition of a structural domain (RWDBD) in Gcn1 proteins that interacts with the RWD domain containing proteins. Biology direct 11 28526057
2024 Emerging Role of GCN1 in Disease and Homeostasis. International journal of molecular sciences 9 38474243
2025 GCN1 couples GCN2 to ribosomal state to initiate amino acid response pathway signaling. Science (New York, N.Y.) 7 41037622
2022 Inducible Systemic Gcn1 Deletion in Mice Leads to Transient Body Weight Loss upon Tamoxifen Treatment Associated with Decrease of Fat and Liver Glycogen Storage. International journal of molecular sciences 6 35328622
2022 A genetic approach to identify amino acids in Gcn1 required for Gcn2 activation. PloS one 6 36441697
2024 Exploring the multifaceted role of GCN1: Implications in cellular responses and disease pathogenesis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 3 38705128
2025 Circadian clock control of interactions between eIF2α kinase CPC-3 and GCN1 with ribosomes regulates rhythmic translation initiation. Proceedings of the National Academy of Sciences of the United States of America 2 39903114
2024 Evidence that Xrn1 is in complex with Gcn1, and is required for full levels of eIF2α phosphorylation. The Biochemical journal 2 38440860
2024 Evidence for interaction of 5,10-methylenetetrahydrofolate reductase (MTHFR) with methylenetetrahydrofolate dehydrogenase (MTHFD1) and general control nonderepressible 1 (GCN1). Biochimie 2 39571719
2025 RAB25/GCN1 signaling promotes endoplasmic reticulum stress to mediate alcohol-associated liver disease progression. Clinical and molecular hepatology 1 40916695

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