Affinage

EIF2A

Eukaryotic translation initiation factor 2 subunit 1 · UniProt P05198

Length
315 aa
Mass
36.1 kDa
Annotated
2026-06-09
48 papers in source corpus 24 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: UniProt preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EIF2A is a single-chain ribosome-associated protein that binds the 40S ribosomal subunit near the mRNA entry channel and modulates translation in a narrow, context-specific manner rather than acting as a core initiation factor [PMID:12133843, PMID:37602404, PMID:bio_10.1101_2025.05.22.655611]. It can function as an eIF2-independent initiator-tRNA carrier, recruiting Met-tRNAi to the 40S P site to support cap-independent translation of specific IRES-bearing mRNAs under conditions of eIF2α phosphorylation, including the HCV IRES and the c-Src IRES, through direct binding to defined IRES stem-loop structures (PMID:21556050, PMID:27899592). At elevated abundance, recombinant EIF2A binds purified 40S subunits and broadly inhibits both cap-dependent and IRES-driven translation, an effect reversed by supplementing additional 40S subunits, indicating a 40S-sequestration mechanism (PMID:37602404). Consistent with a limited physiological role in initiation, genome-wide ribosome profiling in both yeast and human cells found essentially no requirement for EIF2A in global or uORF-mediated translation, even during integrated stress response activation (PMID:38266075, PMID:40600802). Beyond initiation, EIF2A directly enhances SARS-CoV-2 programmed −1 ribosomal frameshifting independently of initiation and preferentially binds CG-rich RNA, with a binding site near the frameshift element contacts on 18S rRNA (PMID:37581984), antagonizes USP10-dependent rescue of 40S ribosomes during ribosome stalling in ribosome-associated quality control [PMID:bio_10.1101_2025.05.22.655611], and supports a translation-independent role in centrosome orientation during cell migration via its C-terminal disordered region (PMID:40749049). EIF2A is dispensable for mammalian viability, but knockout mice develop metabolic syndrome features and altered immune cell populations (PMID:27686860, PMID:34665898). The mammalian factor traces to the historically defined Co-eIF-2A activity, which stimulated and protected eIF-2 ternary complexes and Met-tRNAf binding to 40S ribosomes in reticulocyte lysates (PMID:7356618, PMID:7372648, PMID:3888988).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1981 Medium

    Before the gene was molecularly defined, biochemistry asked whether a cofactor regulated eIF-2 ternary complex behavior; Co-eIF-2A was shown to stimulate and stabilize Met-tRNAf binding and to render it resistant to mRNA-mediated inhibition, establishing an early activity later attributed to EIF2A.

    Evidence antibody inhibition and in vitro ternary complex / Met-tRNAf binding assays with purified Co-eIF-2A from rabbit reticulocytes

    PMID:3888988 PMID:6153053 PMID:7356618 PMID:7372648

    Open questions at the time
    • Molecular identity of the purified factor (reported as ~80 kDa) not definitively tied to the cloned EIF2A gene
    • Mechanism inferred from lysate activity, not reconstitution with defined recombinant protein
  2. 2002 High

    Whether mammalian eIF2A corresponded to a defined gene and participated in initiation was unresolved; cloning and yeast genetics defined the 585-residue single-chain protein, placed it on 40S/80S ribosomes, and showed a synthetic-sick interaction with eIF5B implicating it in initiation but not in GCN4 reinitiation.

    Evidence peptide sequencing, cDNA cloning, ribosome fractionation, and double-knockout/GCN4 reporter genetics in yeast

    PMID:12133843

    Open questions at the time
    • Specific mRNA clients not identified
    • Molecular basis of the eIF5B synthetic interaction unknown
  3. 2011 High

    It was unknown how eIF2A supported translation when eIF2 is inactivated; HCV studies showed eIF2A binds the HCV IRES IIId domain directly and recruits Met-tRNAi to the 40S P site in an eIF2-independent manner, defining an alternative initiator-tRNA carrier activity.

    Evidence siRNA knockdown in HCV-infected cells, direct IRES-domain binding and toeprinting assays, polysome profiling

    PMID:21556050

    Open questions at the time
    • Later contradicted in CRISPR-knockout HAP1 cells
    • PKR-activation role not mechanistically resolved
  4. 2016 High

    To test whether eIF2A-driven IRES translation extends to cellular mRNAs, c-Src work showed direct binding to its IRES stem-loop SL I and stress-specific Met-tRNAi loading that promotes proliferation, generalizing the alternative-initiation model to a host transcript.

    Evidence siRNA knockdown, in vitro IRES binding and toeprinting, bicistronic reporters and proliferation assays under stress

    PMID:27899592

    Open questions at the time
    • Number of physiological cellular IRES clients unclear
    • Stress-specificity mechanism not defined
  5. 2016 Medium

    Whether eIF2A is essential in mammals was tested by gene-trap knockout, which yielded viable mice without gross phenotype, indicating it is not required for viability under standard conditions.

    Evidence gene-trap knockout mouse generation and phenotypic assessment

    PMID:27686860

    Open questions at the time
    • Subtle or stress-conditional phenotypes not examined in this study
    • Molecular cause of dispensability unaddressed
  6. 2018 High

    The proposed eIF2A role in viral IRES translation was directly challenged; clean CRISPR knockouts of eIF2A (and eIF2D) in HAP1 cells supported HCV IRES and Sindbis sgmRNA translation even with phosphorylated eIF2α, contradicting the knockdown-based alternative-initiation reports.

    Evidence CRISPR/Cas9 single and double knockouts in HAP1 cells, IRES luciferase reporters under multiple stress inducers, viral protein synthesis assays

    PMID:28240315 PMID:29487587

    Open questions at the time
    • Discrepancy with knockdown studies unresolved
    • Does not exclude a minor or transcript-restricted role
  7. 2021 Medium

    Whether eIF2A drives non-canonical translation of repeat expansions was tested in myotonic dystrophy models, where eIF2A overexpression increased RAN translation of CCUG- and CAGG-derived products, partly dependent on phospho-eIF2α.

    Evidence CRISPR-edited HEK293T lines (PKR-/-, PERK-/-, eIF2α-S51A), eIF2A overexpression, RAN protein detection

    PMID:33856033

    Open questions at the time
    • Effect shown by overexpression, not endogenous requirement
    • Direct mechanism of RAN initiation enhancement unmapped
  8. 2021 Medium

    The organismal consequences of eIF2A loss were extended; knockout mice showed reduced lifespan, metabolic syndrome features, and altered thymic immune populations, with sex-specific effects, indicating physiological importance despite viability.

    Evidence eIF2A KO mouse metabolic phenotyping, lifespan analysis, flow cytometry, tunicamycin challenge

    PMID:34665898

    Open questions at the time
    • Molecular link between eIF2A loss and metabolic phenotype unknown
    • No ER-stress-response difference observed, leaving mechanism unclear
  9. 2021 Medium

    A conserved developmental requirement was uncovered in Drosophila, where the EIF2A ortholog is essential for spermatogenesis through sperm individualization and F-actin cone formation, with sex-specific splicing.

    Evidence null and hypomorphic transposon alleles, fertility assays, F-actin immunofluorescence in Drosophila

    PMID:34278643

    Open questions at the time
    • Whether this reflects a translational or non-translational role unknown
    • Relevance to mammalian function not established
  10. 2023 High

    The basis of eIF2A's broad inhibitory effect was defined by reconstitution: excess recombinant eIF2A binds purified 40S subunits and inhibits cap-dependent and all classes of IRES translation, with rescue by added 40S, establishing a 40S-sequestration mechanism.

    Evidence recombinant eIF2A purification, mammalian in vitro translation with multiple reporters/IRES types, 40S pull-down and supplementation rescue

    PMID:37602404

    Open questions at the time
    • Physiological relevance of sequestration at endogenous levels unclear
    • Binding interface on 40S not structurally defined
  11. 2023 High

    Translation-independent and quality-control-adjacent activities emerged: eIF2A directly enhances SARS-CoV-2 −1 frameshifting, binds CG-rich RNA near the FSE-ribosome contacts on 18S rRNA, and supports viral replication, separating a frameshifting role from initiation.

    Evidence genome-wide CRISPR screen, eIF2A KO frameshifting validation, viral replication assays, transcriptome-wide RNA-binding analysis

    PMID:37581984

    Open questions at the time
    • Whether eIF2A acts at endogenous host frameshift sites unclear
    • Structural basis of frameshift enhancement undefined
  12. 2023 Medium

    eIF2A (with eIF2D) was shown to be required for IRES-independent translation of enteroviral genomes, supporting recombination when canonical IRES translation is disabled.

    Evidence IRES-inactivating viral mutants, siRNA knockdown of eIF2A and eIF2D, viral replication/recombination assays

    PMID:36689548

    Open questions at the time
    • Direct molecular role versus indirect effect not distinguished
    • Knockdown-based, no reconstitution
  13. 2024 High

    Whether eIF2A is a meaningful initiation factor in vivo was resolved at transcriptome scale; yeast ribosome profiling found no significant translational-efficiency dependence on eIF2A, even during eIF2α phosphorylation, narrowing its initiation role to possibly a single mRNA.

    Evidence genome-wide ribosome profiling of ΔeIF2A yeast under normal and starvation conditions

    PMID:38266075

    Open questions at the time
    • Does not address non-initiation functions (frameshifting, RQC, centrosome)
    • Species-specific differences from mammals not excluded
  14. 2025 High

    The human ribosome-profiling counterpart confirmed minimal involvement of eIF2A in initiation and uORF control, including under ISR activation, consolidating the conclusion that eIF2A is not a general initiation factor.

    Evidence ribosome profiling and uORF/IRES luciferase reporters in eIF2A-depleted HeLa cells under ISR induction

    PMID:40600802

    Open questions at the time
    • Specialized clients still possible but unidentified
    • Mechanism of the rare dependent mRNAs not defined
  15. 2025 Medium

    A translation-independent function was established: proximity labeling identified centrosomal proteins as major eIF2A partners, and eIF2A promotes centrosome composition and orientation during migration via its C-terminal disordered (mRNA-binding) region without requiring ongoing translation.

    Evidence TurboID interactome, co-localization imaging, depletion/migration assays, domain-deletion mutants, translation-inhibition controls

    PMID:40749049

    Open questions at the time
    • Mechanism of centrosome recruitment unknown
    • How the disordered region acts at the centrosome unclear
  16. 2025 Medium

    A role in ribosome-associated quality control was proposed: eIF2A binds near the 40S mRNA entry channel, interacts with G3BP1-USP10 and RPS2/RPS3, and antagonizes USP10-dependent 40S rescue, shaping 40S turnover upon stalling.

    Evidence TurboID + mass spectrometry, polysome gradients, dynamic SILAC, eIF2A KO cells, stalling and ubiquitination assays (preprint)

    PMID:bio_10.1101_2025.05.22.655611

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • Direct versus indirect antagonism of USP10 not resolved
    • Structural detail of the 40S contact not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Despite agreement that eIF2A is not a core initiation factor, the unifying molecular activity linking its 40S-binding, frameshift-enhancing, RQC, and centrosomal functions remains undefined.
  • No structure of eIF2A on the 40S ribosome
  • The identity and number of genuine endogenous mRNA clients unknown
  • Whether RNA-binding underlies the centrosomal role is untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4 GO:0140104 molecular carrier activity 3 GO:0140110 transcription regulator activity 1
Localization
GO:0005840 ribosome 3 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-8953854 Metabolism of RNA 3
Partners
EEF1A1EIF2DG3BP1RPS2RPS3USP10

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Mammalian eIF2A is a 585 amino acid, single-chain protein encoded by a gene on chromosome 3. The yeast homolog (YGR054W) localizes on both 40S and 80S ribosomes. A double knockout of yeast eIF2A and eIF5B yields a synthetically sick slow-growth phenotype, suggesting eIF2A participates in translation initiation. eIF2A does not appear to participate in re-initiation, as the ΔeIF2A strain shows the same level of GCN4 induction with amino acid starvation as wild-type yeast. Peptide sequencing of rabbit reticulocyte eIF2A, cDNA/EST cloning, HA-tagging and ribosome fractionation in yeast, genetic double-knockout analysis, GCN4-lacZ reporter assay The Journal of biological chemistry High 12133843
2009 In yeast, eIF2A acts as a negative regulator of IRES-mediated (cap-independent) translation under normal cellular conditions. eIF2A-mediated repression is not specific to the URE2 IRES; GIC1 and PAB1 IRES elements are also repressed by eIF2A. The stability of secondary structure within the URE2 IRES is not required for eIF2A-dependent repression. Monocistronic reporter assays in ΔeIF2A yeast strains, mutational analysis of URE2 IRES stem-loop structures RNA (New York, N.Y.) Medium 19861427
2011 In yeast, eIF2A abundance is reduced at both mRNA and protein levels during ethanol stress or heat shock; eIF2A protein is also post-translationally modified during ethanol stress. eIF2A interacts with eEF1A (identified by immunoprecipitation-mass spectrometry), and this interaction increases during ethanol stress, correlating with increased IRES-mediated translation from the URE2 IRES. Western blot and qRT-PCR for eIF2A levels under stress; immunoprecipitation-mass spectrometry to identify eEF1A as binding partner; IRES reporter assays in ΔeIF2A yeast PloS one Medium 21915340
2011 eIF2A mediates translation of HCV mRNA under stress conditions when eIF2α is phosphorylated. eIF2A directly interacts with the IIId domain of the HCV IRES, and this direct interaction is required for eIF2A-dependent translation. eIF2A acts as an alternative initiator tRNA-binding protein that recruits Met-tRNAi to the P site of the 40S ribosomal subunit in an eIF2-independent manner. eIF2A also promotes eIF2α phosphorylation by activating the eIF2α kinase PKR during HCV infection. siRNA knockdown of eIF2A in HCV-infected cells, in vitro binding assays between eIF2A and HCV IRES domains, toeprinting assays, polysome profiling, PKR activation assays The EMBO journal High 21556050
2016 eIF2A is responsible for stress-resistant translation of c-Src mRNA via its IRES element. eIF2A facilitates tRNAi loading onto the 40S ribosomal subunit in a c-Src mRNA-dependent manner. A direct interaction between eIF2A and a stem-loop structure (SL I) in the c-Src IRES is required for IRES-dependent translation under stress conditions but not under normal conditions. eIF2A-dependent translation of c-Src mRNA promotes cell proliferation under stress. siRNA knockdown of eIF2A, in vitro binding assays between eIF2A and c-Src IRES SL I, toeprinting assays, bicistronic reporter assays under stress conditions, cell proliferation assays Nucleic acids research High 27899592
2016 In an eIF2A knockout mouse strain (gene trap between exons 1 and 2), mice are viable with no apparent gross phenotype, suggesting eIF2A is not essential for viability in mammals under standard conditions. Gene-trap knockout mouse generation, viability and phenotypic assessment Cell cycle (Georgetown, Tex.) Medium 27686860
2017 Translation of Sindbis virus subgenomic mRNA is independent of eIF2A and eIF2D. HAP1 cells knocked-out for eIF2A, eIF2D, or both via CRISPR/Cas9 showed comparable Sindbis virus infection and viral protein synthesis to wild-type cells, even when eIF2α was phosphorylated. This is a negative finding: eIF2A and eIF2D are not required for sgmRNA translation when eIF2α is phosphorylated. CRISPR/Cas9 knockout of eIF2A and eIF2D in HAP1 cells, Sindbis virus infection, siRNA silencing, measurement of viral protein synthesis by Western blot Scientific reports High 28240315
2018 Neither eIF2A nor eIF2D participates in HCV IRES-driven translation in human cells. Human HAP1 cells depleted for eIF2A, eIF2D, or both were able to synthesize luciferase from an HCV IRES-bearing mRNA even when eIF2α was phosphorylated. This is a negative finding contradicting earlier reports that eIF2A mediates HCV IRES translation under stress. HAP1 cells depleted for eIF2A and/or eIF2D via CRISPR/Cas9, HCV IRES luciferase reporter assays under multiple stress conditions (arsenite, thapsigargin, tunicamycin, salubrinal) Frontiers in microbiology High 29487587
2021 eIF2A knockout mice exhibit decreased life span, metabolic syndrome features (impaired lipid homeostasis, glucose tolerance defects, insulin resistance), and reduced B lymphocytes and dendritic cells in thymic medulla. Effects differ between male and female mice. Pharmacological ER stress induction with tunicamycin did not reveal substantial differences between KO and wild-type mice in ER stress response. eIF2A KO mouse model, metabolic phenotyping (glucose tolerance test, insulin resistance assays), lifespan analysis, flow cytometry of thymic cell populations, tunicamycin treatment FASEB journal Medium 34665898
2021 Overexpression of eIF2A increases RAN (repeat-associated non-AUG) translation of both LPAC (from CCUG repeats) and QAGR (from CAGG repeats) proteins in DM2 myotonic dystrophy. The effect of eIF2A on QAGR (CAGG transcripts lacking efficient close-cognate codons) is novel and dependent on phosphorylated eIF2α, whereas eIF2A effects on LPAC are partially independent of p-eIF2α. CRISPR/Cas9-edited HEK293T cell lines (PKR-/-, PERK-/-, eIF2α-S51A), eIF2A overexpression, RAN protein measurement by Western blot and immunofluorescence Human molecular genetics Medium 33856033
2021 Drosophila EIF2A (encoded by CG7414) is essential for spermatogenesis. Loss of function (Mi{Mic} null allele) causes male sterility due to failure of sperm individualization, defects in F-actin cones, and failure to form and maintain cystic bulges. The Mi{Mic} null allele is homozygous lethal, while a hypomorphic allele causes male sterility and female fertility. The gene undergoes sex-specific splicing regulating male-specific expression. Transposon insertion mutant alleles in Drosophila (null Mi{Mic} and hypomorphic PBac), fertility assays, immunofluorescence of F-actin cones, genetic analysis Developmental dynamics Medium 34278643
2023 Increased levels of recombinant human eIF2A inhibit translation of multiple reporter mRNAs in a mammalian in vitro translation system, including those translated by cognate and near-cognate start codons, and inhibit all four types of cap-independent viral IRES-driven translation including the CrPV IGR IRES (which requires no initiation factors or initiator tRNA). Supplementation with additional 40S subunits rescues eIF2A-mediated inhibition. Pull-down assays demonstrate direct binding between recombinant eIF2A and purified 40S subunits, supporting a model that excess eIF2A sequesters 40S ribosomal subunits. Purification of recombinant human eIF2A from E. coli and insect cells, mammalian in vitro translation assays with multiple reporter mRNAs and IRES types, 40S subunit supplementation rescue experiment, pull-down assays with purified 40S subunits Nucleic acids research High 37602404
2023 eIF2A specifically and directly enhances SARS-CoV-2 programmed -1 ribosomal frameshifting (-1 PRF), independently of changes in translation initiation. Loss of eIF2A reduces SARS-CoV-2 replication in cells. Transcriptome-wide analysis shows eIF2A preferentially binds CG-rich RNA motifs, including a region within 18S rRNA near the contacts between the SARS-CoV-2 frameshift-stimulatory element (FSE) and the ribosome. Genome-wide CRISPR-Cas9 knockout screen for -1 PRF regulators, eIF2A KO cell validation of frameshifting, SARS-CoV-2 replication assays in KO cells, transcriptome-wide RNA binding analysis (CLIP-seq or equivalent) Cell reports High 37581984
2023 eIF2A and eIF2D are required for IRES-independent translation of enteroviral genomes. In cells with complete inactivation of IRES-mediated translation, sufficient translation of the nonstructural region still occurs to support recombination, and this IRES-independent translation depends on eIF2A and eIF2D. IRES-inactivating mutations in enteroviral genome, siRNA knockdown of eIF2A and eIF2D, viral replication and recombination assays PLoS biology Medium 36689548
2024 Yeast eIF2A has a minimal role in translation initiation in vivo. Ribosome profiling of ΔeIF2A yeast showed no significant translational efficiency reductions for any mRNAs in non-starved cells, and only minor reductions in starved cells with phosphorylated eIF2α. No evidence was found that eIF2A altered IRES-mediated translation or translation of mRNAs with uORFs initiated by AUG or near-cognate codons. Very few mRNAs (possibly only one) appear to employ eIF2A for Met-tRNAi recruitment in yeast. Ribosome profiling (genome-wide) of ΔeIF2A yeast under normal and amino acid starvation conditions, bioinformatic analysis of translational efficiencies eLife High 38266075
2025 Human eIF2A has a minimal role in translation initiation and uORF-mediated translational control in HeLa cells. Ribosome profiling and luciferase reporter assays in eIF2A-depleted HeLa cells, including conditions of integrated stress response activation, detected no role for eIF2A in translation initiation. Ribosome profiling in eIF2A-depleted HeLa cells, luciferase reporter assays for uORF-containing and IRES-containing mRNAs, ISR activation with chemical inducers eLife High 40600802
2025 eIF2A regulates cell migration in a translation-independent manner. Interactome studies (proximity labeling) identified centrosomal proteins as major binding partners of eIF2A. eIF2A colocalizes with the centrosome, enhances centrosome composition, and promotes centrosome orientation during cell migration. This function requires the C-terminal disordered region of eIF2A involved in mRNA binding, but does not require ongoing translation. TurboID proximity labeling interactome, co-localization imaging (eIF2A with centrosomal markers), eIF2A depletion with migration assays, domain deletion mutants, translation inhibition controls Science advances Medium 40749049
2025 eIF2A has a novel function in ribosome-associated quality control (RQC). Using TurboID proximity labeling combined with polysome gradients and mass spectrometry, eIF2A's binding site was mapped close to the mRNA entry channel of the 40S ribosomal subunit. eIF2A strongly interacts with G3BP1-USP10 complexes and ribosomal proteins RPS2 and RPS3. In the absence of eIF2A, RPS2 and RPS3 ubiquitination is diminished specifically upon ribosome stalling. eIF2A antagonizes USP10-dependent rescue of 40S ribosomes, resulting in altered turnover of 40S subunits upon cellular stress. TurboID proximity labeling + mass spectrometry, polysome gradient fractionation, dynamic SILAC mass spectrometry, eIF2A knockout cells, ribosome stalling assays, ubiquitination measurements bioRxivpreprint Medium bio_10.1101_2025.05.22.655611
1980 Co-eIF-2A (an activity later attributed to a component of what became eIF2A) is absolutely required for protein synthesis in reticulocyte lysates; antibody inhibition of Co-eIF-2A cannot be reversed by eIF-2, establishing a non-redundant requirement. Co-eIF-2A stimulates eIF-2-dependent ternary complex formation and protects ternary complexes from dissociation by aurintricarboxylic acid. Co-eIF-2A does not interact with free eIF-2 but specifically with the preformed ternary complex. Antibody inhibition of reticulocyte lysate protein synthesis, reversal experiments with purified factors, fluorescence polarization with dansyl-labeled Co-eIF-2A The Journal of biological chemistry Medium 7356618 7372648
1981 Co-eIF-2A reverses mRNA inhibition of ternary complex formation by eIF-2. At low mRNA concentrations, mRNAs strongly inhibit ternary complex (Met-tRNAf·eIF-2·GTP) formation and dissociate preformed ternary complexes; excess Co-eIF-2A renders Met-tRNAf binding to eIF-2 fully resistant to this mRNA inhibition. Other cofactors (Co-eIF-2B and Co-eIF-2C) did not reverse mRNA inhibition. In vitro ternary complex formation assays with purified Co-eIF-2A, mRNA titration, filter-binding assays The Journal of biological chemistry Medium 6153053
1985 An 80 kDa polypeptide (Co-eIF-2A80) was purified to homogeneity from rabbit reticulocytes and shown to stimulate Met-tRNAf binding to eIF-2 in a manner resistant to aurintricarboxylic acid. Antibodies against Co-eIF-2A80 strongly inhibited protein synthesis in reticulocyte lysates and blocked eIF-2 and Co-eIF-2-promoted Met-tRNAf binding to 40S ribosomes. Limited proteolysis mapped the protein to the 80 kDa band within the Co-eIF-2 complex. Protein purification to homogeneity, in vitro translation assays, antibody inhibition, limited V8 protease mapping The Journal of biological chemistry Medium 3888988
2015 EIF2A phosphorylation is induced in leukemia cells by FK866 (NAMPT inhibitor) via the LKB1-AMPK-EIF2A axis and is responsible for translational arrest and cell survival. Expression of a non-phosphorylatable EIF2A mutant in Jurkat cells enhanced sensitivity to FK866, confirming that EIF2A phosphorylation mediates protein synthesis arrest as a survival mechanism. FK866 treatment of leukemia cell lines, ectopic expression of non-phosphorylatable EIF2A mutant, AMPK/LKB1 silencing, polysome profiling BMC cancer Medium 26542945
2019 EIF2A is essential for cancer cell survival after paclitaxel-mediated integrated stress response both in vitro and in vivo. Paclitaxel activates the EIF2AK3/EIF2AK4-pEIF2S1-ATF4 axis, and EIF2A is required for maintenance of redox homeostasis by supporting expression of antioxidant enzymes (HMOX1, SHMT2, SLC7A11) in this context. siRNA knockdown and overexpression of EIF2A in breast cancer cells, xenograft mouse models, ROS scavenger rescue experiment (Trolox), Western blot for ISR markers Journal of cellular and molecular medicine Medium 31211507

Source papers

Stage 0 corpus · 48 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 eIF2A mediates translation of hepatitis C viral mRNA under stress conditions. The EMBO journal 102 21556050
2008 Eif-2a protects brainstem motoneurons in a murine model of sleep apnea. The Journal of neuroscience : the official journal of the Society for Neuroscience 72 18305250
2016 Activation of the EIF2AK4-EIF2A/eIF2α-ATF4 pathway triggers autophagy response to Crohn disease-associated adherent-invasive Escherichia coli infection. Autophagy 64 26986695
2002 Characterization of mammalian eIF2A and identification of the yeast homolog. The Journal of biological chemistry 60 12133843
2020 A Retrospective on eIF2A-and Not the Alpha Subunit of eIF2. International journal of molecular sciences 52 32192132
2019 EIF2A promotes cell survival during paclitaxel treatment in vitro and in vivo. Journal of cellular and molecular medicine 48 31211507
2017 Kinases of eIF2a Switch Translation of mRNA Subset during Neuronal Plasticity. International journal of molecular sciences 41 29065505
1988 Natural mRNA is required for directing Met-tRNA(f) binding to 40S ribosomal subunits in animal cells: involvement of Co-eIF-2A in natural mRNA-directed initiation complex formation. Biochemistry 34 3233204
2016 An mRNA-specific tRNAi carrier eIF2A plays a pivotal role in cell proliferation under stress conditions: stress-resistant translation of c-Src mRNA is mediated by eIF2A. Nucleic acids research 30 27899592
2017 Translation of Sindbis Subgenomic mRNA is Independent of eIF2, eIF2A and eIF2D. Scientific reports 28 28240315
2018 The Initiation Factors eIF2, eIF2A, eIF2D, eIF4A, and eIF4G Are Not Involved in Translation Driven by Hepatitis C Virus IRES in Human Cells. Frontiers in microbiology 27 29487587
2016 The eIF2A knockout mouse. Cell cycle (Georgetown, Tex.) 27 27686860
2011 Insights into the role of yeast eIF2A in IRES-mediated translation. PloS one 27 21915340
2015 Polypeptide from Chlamys farreri suppresses ultraviolet-B irradiation-induced apoptosis through restoring ER redox homeostasis, scavenging ROS generation, and suppressing the PERK-eIF2a-CHOP pathway in HaCaT cells. Journal of photochemistry and photobiology. B, Biology 26 26142622
2019 miR‑195 promotes LPS‑mediated intestinal epithelial cell apoptosis via targeting SIRT1/eIF2a. International journal of molecular medicine 25 31894250
2009 Characterization of the functional role of nucleotides within the URE2 IRES element and the requirements for eIF2A-mediated repression. RNA (New York, N.Y.) 24 19861427
2021 eIF2A-knockout mice reveal decreased life span and metabolic syndrome. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 22 34665898
2021 The alternative initiation factor eIF2A plays key role in RAN translation of myotonic dystrophy type 2 CCUG•CAGG repeats. Human molecular genetics 21 33856033
1985 Protein synthesis in rabbit reticulocytes. Purification and properties of an Mr 80,000 polypeptide (Co-eIF-2A80) with Co-eIF-2A activity. The Journal of biological chemistry 21 3888988
1985 Purification and properties of eukaryotic initiation factor 2 and its ancillary protein factor (Co-eIF-2A) from yeast Saccharomyces cerevisiae. The Journal of biological chemistry 21 3888989
1980 Protein synthesis in rabbit reticulocytes. Demonstration of the requirements for eIF-2 and Co-eIF-2A for peptide chain initiation using immune sera. The Journal of biological chemistry 21 7356618
2011 Endoplasmic reticulum stress decreases intracellular thyroid hormone activation via an eIF2a-mediated decrease in type 2 deiodinase synthesis. Molecular endocrinology (Baltimore, Md.) 19 22053000
1981 Protein synthesis in rabbit reticulocytes. Co-eIF-2A reverses mRNA inhibition of ternary complex (Met-tRNAf.eIF-2.GTP) formation by eIF-2. The Journal of biological chemistry 17 6153053
2015 EIF2A-dependent translational arrest protects leukemia cells from the energetic stress induced by NAMPT inhibition. BMC cancer 13 26542945
2018 The Effect of Culture Temperature on the Aggregation of Recombinant TNFR-Fc is Regulated by the PERK-eIF2a Pathway in CHO Cells. Protein and peptide letters 12 29848262
2023 Genome-wide CRISPR screens identify noncanonical translation factor eIF2A as an enhancer of SARS-CoV-2 programmed -1 ribosomal frameshifting. Cell reports 11 37581984
1980 Protein synthesis in rabbit reticulocytes. A study of the mechanism of interreaction of fluorescently labeled co-eIF-2A with eIF-2 using fluorescence polarization. The Journal of biological chemistry 11 7372648
2024 To initiate or not to initiate: A critical assessment of eIF2A, eIF2D, and MCT-1·DENR to deliver initiator tRNA to ribosomes. Wiley interdisciplinary reviews. RNA 10 38433101
2023 The enterovirus genome can be translated in an IRES-independent manner that requires the initiation factors eIF2A/eIF2D. PLoS biology 10 36689548
2023 Increased levels of eIF2A inhibit translation by sequestering 40S ribosomal subunits. Nucleic acids research 10 37602404
2024 Yeast eIF2A has a minimal role in translation initiation and uORF-mediated translational control in vivo. eLife 8 38266075
2024 African swine fever virus RNA polymerase subunits C315R and H359L inhibition host translation by activating the PKR-eIF2a pathway and suppression inflammatory responses. Frontiers in microbiology 8 39380677
2022 PKR-Mediated Phosphorylation of eIF2a and CHK1 Is Associated with Doxorubicin-Mediated Apoptosis in HCC1143 Triple-Negative Breast Cancer Cells. International journal of molecular sciences 7 36555509
2021 U three protein 14a (UTP14A) promotes tumour proliferation and metastasis via the PERK/eIF2a/GRP78 signalling pathway in oesophageal squamous cell carcinoma. Journal of Cancer 7 33391409
2021 Unconventional translation initiation factor EIF2A is required for Drosophila spermatogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 7 34278643
2021 Alendronate Alleviated Femoral Head Necrosis and Upregulated BMP2/EIF2AK3/EIF2A/ATF4 Pathway in Liquid Nitrogen Treated Rats. Drug design, development and therapy 5 33935494
2025 Human eIF2A has a minimal role in translation initiation and in uORF-mediated translational control in HeLa cells. eLife 4 40600802
2023 Integrating network pharmacology and experimental models to examine the mechanisms of corosolic acid in preventing hepatocellular carcinoma progression through activation PERK-eIF2a-ATF4 signaling. Naunyn-Schmiedeberg's archives of pharmacology 3 37294427
2018 PERK, mTORC1 and eEF2 interplay during long term potentiation: An Editorial for 'Genetic removal of eIF2a kinase PERK in mice enables hippocampal L-LTP independent of mTORC1 activity' on page 133. Journal of neurochemistry 3 30133715
2007 [Genetic polymorphisms of MxA protein and eIF-2a-reg2 and their responses to interferon treatment in patients with chronic hepatitis B]. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 3 17407708
2025 eIF2A regulates cell migration in a translation-independent manner. Science advances 2 40749049
2010 [Role of PERK/eIF2a signaling pathway in hepatocyte apoptosis of alcoholic liver injury rats]. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 2 21059295
2024 Adjuvant alum regulates the eIF2a-GATA3 axis in CD4+ T cells to influence allergen immunotherapy. Scandinavian journal of immunology 1 39562297
2014 Gene cloning of an important eukaryotic translation initiation factor family, eIF2A gene in halophytic Leymus chinensis (Trin.). Biotechnology, biotechnological equipment 1 26019549
1986 Protein synthesis in yeast Saccharomyces cerevisiae. Purification of Co-eIF-2A and 'mRNA-binding factor(s)' and studies of their roles in Met-tRNAf.40S.mRNA complex formation. European journal of biochemistry 1 3096729
2025 Super-enhancer PPP1R15B/EIF2A axis characterizes aggressive drug-tolerant persister cells in Glioblastoma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 0 40639044
2025 Correction: PERK/eIF2a pathway affected the thyroid hormone synthetic in hypertensive disorders of pregnancy rats. Frontiers in endocrinology 0 40979716
2023 Yeast eIF2A has a minimal role in translation initiation and uORF-mediated translational control in vivo. bioRxiv : the preprint server for biology 0 37986989

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