Affinage

EIF4G2

Eukaryotic translation initiation factor 4 gamma 2 · UniProt P78344

Round 2 corrected
Length
907 aa
Mass
102.4 kDa
Annotated
2026-04-28
130 papers in source corpus 16 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EIF4G2 (DAP5/NAT1/p97) is a non-canonical translation initiation factor that lacks the eIF4E-binding domain of eIF4G1 but retains a single eIF4A-binding site and eIF3-interaction capability, enabling it to drive both cap-independent (IRES-mediated) and cap-dependent but eIF4E/mTORC1-independent translation of select mRNAs (PMID:9372926, PMID:25779044, PMID:34848685). During mitosis and cellular stress, EIF4G2 sustains translation of pro-survival (Bcl-2), cell-cycle (CDK1), and stress-response (p53, HIAP2) mRNAs through IRES elements, while in unstressed cells it facilitates leaky scanning through translated uORFs and translation re-initiation on mRNAs with long structured 5′ leaders encoding signaling kinases and phosphatases (PMID:18450493, PMID:18003655, PMID:35018467, PMID:36473845). EIF4G2 is dispensable for bulk translation and primary tumor growth but essential for embryonic differentiation, stem-cell metabolic reprogramming, Treg cell commitment, EMT-driven metastasis, and activity-dependent local dendritic translation in neurons, where depolarization-induced phosphorylation and dendritic recruitment enable uORF-mediated translational control of plasticity-related mRNAs (PMID:11032820, PMID:27664238, PMID:34848685, PMID:37314929, PMID:38589584). Viral 2A proteases cleave EIF4G2 to generate fragments that differentially support pro-apoptotic versus cap-dependent translation, a mechanism exploited during coxsackievirus B3 infection (PMID:26586572).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1997 High

    Establishing that EIF4G2 is structurally distinct from eIF4G1 — it possesses only one eIF4A-binding domain and lacks the eIF4E-binding region — answered the foundational question of whether this homolog functions through the same initiation complex as canonical eIF4G.

    Evidence Deletion mapping and in vitro binding assays with recombinant EIF4G2 and eIF4A

    PMID:9372926

    Open questions at the time
    • No structural model of the EIF4G2–eIF4A interface
    • Functional consequence of single versus dual eIF4A sites not tested in translation assays
  2. 1999 Medium

    Identification of the EIF4G2–Mnk1 interaction raised the possibility that EIF4G2 modulates eIF4E phosphorylation by sequestering Mnk1 away from eIF4G1, providing a potential mechanism for translational regulation beyond direct mRNA recruitment.

    Evidence Co-immunoprecipitation and in vitro binding assays

    PMID:9878069

    Open questions at the time
    • Functional consequence of Mnk1 sequestration on eIF4E phosphorylation not directly demonstrated
    • No reciprocal co-IP or endogenous complex validation reported
  3. 2000 High

    Genetic knockout in mice revealed that EIF4G2 is essential not for global translation or proliferation but specifically for embryonic differentiation and selective gene expression, reframing it as a regulator of cell-fate-specific translation programs.

    Evidence NAT1-null mouse embryos; retinoic acid differentiation assay in ES cells; teratoma assay

    PMID:11032820

    Open questions at the time
    • Direct mRNA targets mediating the differentiation defect not identified
    • Whether the lethality is purely translational or involves other functions of EIF4G2 not resolved
  4. 2008 High

    Demonstrating that EIF4G2 drives IRES-mediated translation of Bcl-2 and CDK1 specifically during mitosis answered how cells maintain pro-survival and cell-cycle protein levels when cap-dependent translation is globally suppressed.

    Evidence siRNA knockdown; polysome profiling; bicistronic IRES reporters; ectopic Bcl-2/CDK1 rescue of apoptosis

    PMID:18450493

    Open questions at the time
    • How EIF4G2 is activated during M phase is unclear
    • Whether all mitotic IRES activity is EIF4G2-dependent or partially redundant with other factors
  5. 2007 High

    A positive feedback loop was identified in which ER stress drives EIF4G2 upregulation via its own IRES, and full-length EIF4G2 (not its caspase-cleaved fragment) activates HIAP2 IRES translation, establishing EIF4G2 as a stress-responsive auto-amplifying translation regulator.

    Evidence Polysome profiling under ER stress; bicistronic IRES reporters; caspase inhibition

    PMID:18003655

    Open questions at the time
    • Whether the autoregulatory IRES loop is conserved across stress types beyond ER stress
    • Structural basis of how EIF4G2 recognizes its own IRES is unknown
  6. 2013 High

    The first demonstration of direct EIF4G2 binding to an mRNA (the p53 IRES) established that EIF4G2 acts as a genuine RNA-binding translation factor rather than solely a scaffold, and showed preferential promotion of Δ40p53 isoform translation.

    Evidence RNA immunoprecipitation (in vitro and in vivo); bicistronic reporters; polysome profiling; siRNA knockdown

    PMID:23318444

    Open questions at the time
    • RNA-binding specificity determinants and structural basis of IRES recognition not defined
    • Generality of direct mRNA binding beyond the p53 IRES not established at this point
  7. 2015 High

    Biochemical dissection showed EIF4G2 forms a distinct initiation complex with eIF2β and eIF4AI (excluding eIF4E), explaining its selective engagement with cap-independent translation and its dispensability for canonical cap-dependent initiation.

    Evidence Reciprocal co-immunoprecipitation; IRES reporter assays; in vitro translation; knockdown/rescue

    PMID:25779044

    Open questions at the time
    • Stoichiometry and assembly order of the EIF4G2–eIF2β–eIF4AI complex not determined
    • Whether additional factors are required for complex specificity is unknown
  8. 2015 High

    Viral protease cleavage of EIF4G2 at G434 by CVB3 2A protease generates functionally asymmetric fragments — the N-terminal fragment drives pro-apoptotic p53 IRES translation but not pro-survival Bcl-2, while the C-terminal fragment dominantly inhibits cap-dependent translation — revealing how viruses exploit EIF4G2 processing to rewire host translation.

    Evidence Site-directed mutagenesis; overexpression of truncation mutants; IRES reporters; viral replication assays; subcellular fractionation

    PMID:26586572

    Open questions at the time
    • Whether other viral proteases cleave EIF4G2 at the same or different sites
    • In vivo pathogenic significance of the N-terminal nuclear translocation not explored
  9. 2016 High

    Translatomic profiling in human embryonic stem cells revealed that EIF4G2 selectively translates mRNAs encoding mitochondrial and chromatin-remodeling proteins required for the metabolic switch from glycolysis to oxidative respiration during differentiation, providing a molecular explanation for the embryonic lethality of EIF4G2 knockout.

    Evidence Polysome-seq in hESCs; siRNA knockdown; mitochondrial morphology and respiration assays; embryoid body formation

    PMID:27664238

    Open questions at the time
    • Whether EIF4G2 directly binds all identified target mRNAs or acts indirectly for some
    • How EIF4G2 target specificity is established during the pluripotency-to-differentiation transition
  10. 2021 High

    Discovery of the DAP5/eIF3d cap-dependent alternative translation complex revealed that EIF4G2 can drive cap-dependent translation independently of eIF4E and mTORC1, and that this mechanism is critical for TGF-β-induced Treg differentiation — fundamentally broadening the EIF4G2 paradigm beyond IRES-only activity.

    Evidence Ribosome profiling; siRNA knockdown; T cell differentiation assays; mTORC1 inhibition

    PMID:34848685

    Open questions at the time
    • How eIF3d cap-binding replaces eIF4E in this complex is not structurally resolved
    • Whether DAP5/eIF3d complex operates in all cell types or is context-restricted
  11. 2022 High

    Two complementary ribosome profiling studies established that EIF4G2 promotes leaky scanning through translated uORFs and facilitates translation re-initiation on the main CDS of mRNAs with long structured 5′ leaders, particularly those encoding signaling kinases and phosphatases — providing a mechanistic basis for EIF4G2's selective translational control beyond IRES elements.

    Evidence Ribosome profiling; luciferase reporters with uORF mutations; siRNA knockdown

    PMID:35018467 PMID:36473845

    Open questions at the time
    • Whether EIF4G2 directly contacts uORF-containing mRNA leaders or acts through protein-protein interactions during scanning
    • Relative contribution of leaky scanning versus re-initiation for individual target mRNAs
  12. 2023 High

    The DAP5/eIF3d complex was shown to be essential for EMT, invasion, and metastasis in breast cancer by selectively translating EMT transcription factors, integrins, metalloproteinases, and angiogenesis factors — demonstrating that the non-canonical EIF4G2 translation program drives tumor progression at the metastatic rather than primary growth stage.

    Evidence Genome-wide translatomics; DAP5 KO; human and murine breast cancer xenograft models; migration/invasion assays

    PMID:37314929

    Open questions at the time
    • Whether DAP5/eIF3d targeting in established tumors can suppress metastasis therapeutically
    • Whether the metastatic translation program overlaps with the differentiation program in stem cells
  13. 2024 High

    Activity-dependent phosphorylation and dendritic recruitment of EIF4G2 in neurons enables uORF-mediated translation of plasticity-related mRNAs upon depolarization, establishing a local translational control mechanism for long-term potentiation and revealing that uORF sequences are sufficient to confer EIF4G2-dependent regulation.

    Evidence APEX proximity labeling; CLIP; ribosome profiling; mass spectrometry; KCl/DHPG depolarization in primary cortical neurons; EIF4G2 knockdown

    PMID:38589584

    Open questions at the time
    • Identity of the kinase(s) responsible for depolarization-induced EIF4G2 phosphorylation
    • Whether EIF4G2-dependent dendritic translation is required for learning and memory in vivo
    • Structural basis of EIF4G2 recognition of uORF-containing mRNAs in dendrites

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of EIF4G2 RNA selectivity, the kinase signaling pathways that activate EIF4G2 in different contexts (mitosis, stress, neuronal depolarization), and whether the IRES-driven and DAP5/eIF3d cap-dependent mechanisms represent distinct or overlapping target mRNA pools.
  • No high-resolution structure of EIF4G2 bound to an mRNA target
  • Kinases phosphorylating EIF4G2 upon neuronal depolarization or during mitosis are unidentified
  • Systematic comparison of IRES-dependent versus eIF3d-cap-dependent EIF4G2 target mRNAs not performed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0045182 translation regulator activity 8 GO:0060090 molecular adaptor activity 3 GO:0003723 RNA binding 2
Localization
GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-1266738 Developmental Biology 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-1643685 Disease 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-112316 Neuronal System 1 R-HSA-1640170 Cell Cycle 1 R-HSA-168256 Immune System 1
Partners
EIF2S2EIF3DEIF4A1MKNK1
Complex memberships
DAP5/eIF3d alternative translation complexDAP5–eIF2β–eIF4AI initiation complex

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 EIF4G2 (p97/DAP5) binds eIF4A only through its amino-terminal proximal region (homologous to the middle domain of eIF4G1), unlike full-length eIF4G1 which has two separate eIF4A binding domains. This single eIF4A binding site distinguishes EIF4G2 from eIF4G1 and suggests a mechanistically distinct role in translation. Binding domain mapping by deletion analysis and in vitro binding assays Molecular and cellular biology High 9372926
1999 EIF4G2 (p97) interacts with Mnk1 kinase through its C-terminal region, raising the possibility that p97 sequesters Mnk1 and thereby blocks phosphorylation of eIF4E by competing with eIF4G1 for Mnk1 binding. Co-immunoprecipitation and in vitro binding assays The EMBO journal Medium 9878069
2000 Genetic disruption of NAT1/EIF4G2 in mice causes lethality during gastrulation. NAT1-null embryonic stem cells are normal in proliferation and global translation but exhibit a specific impairment in differentiation: they are resistant to retinoic acid-induced differentiation, and retinoic acid-responsive gene expression (e.g., p21WAF1) is selectively reduced. This establishes EIF4G2 as essential for specific gene expression pathways required for embryonic differentiation, not for bulk translation. Gene knockout in mice; teratoma assay; retinoic acid differentiation assay; gene expression profiling The EMBO journal High 11032820
2008 DAP5/EIF4G2 is required for cell survival during mitosis (M phase) in non-stressed cells. Knockdown of DAP5 induces M phase-specific caspase-dependent apoptosis. DAP5 promotes cap-independent (IRES-driven) translation of Bcl-2 and CDK1 mRNAs during mitosis; knockdown reduces Bcl-2 mRNA association with polysomes, decreases CDK1 protein and its substrate phosphorylation, and ectopic expression of either Bcl-2 or CDK1 partially rescues apoptosis. siRNA knockdown; polysome profiling; bicistronic reporter assays for IRES activity; rescue by ectopic protein expression Molecular cell High 18450493
2007 DAP5/EIF4G2 expression is selectively upregulated during endoplasmic reticulum (ER) stress through recruitment of its own mRNA into polysomes via the DAP5 IRES, establishing a positive feedback loop. Full-length DAP5 (not caspase-cleaved p86) is required for ER-stress-induced activation of the HIAP2 IRES in a caspase-independent manner, while induction of HIAP2 translation requires caspase-mediated cleavage of DAP5. Polysome profiling; siRNA knockdown; bicistronic IRES reporter assays; caspase inhibition experiments Nucleic acids research High 18003655
2013 DAP5/EIF4G2 promotes IRES-driven translation of full-length p53 and the Δ40p53 isoform, with preferential promotion of translation from the second IRES within the p53 coding sequence. DAP5 directly binds p53 IRES elements both in vitro and in vivo (first demonstration of direct DAP5-mRNA binding), and DAP5 knockdown shifts p53 mRNA to lighter polysomes and reduces Δ40p53-dependent transcriptional activation of 14-3-3σ. Bicistronic reporter assays; polysome profiling; RNA immunoprecipitation (in vitro and in vivo); siRNA knockdown Oncogene High 23318444
2015 DAP5/EIF4G2 associates with eIF2β and eIF4AI (but not eIF4E) to stimulate IRES-dependent translation of cellular mRNAs, while being dispensable for cap-dependent translation. This mechanistic dissection demonstrates that DAP5 forms a distinct initiation complex that selectively drives cap-independent translation. Co-immunoprecipitation; knockdown/rescue; IRES reporter assays; in vitro translation Nucleic acids research High 25779044
2015 miR-139-5p suppresses EIF4G2 expression in acute myeloid leukemia (AML), reducing overall protein synthesis while specifically inducing translation of cell cycle inhibitor p27Kip1. EIF4G2 knockdown recapitulates the mir-139 phenotype (cell cycle arrest, apoptosis), and EIF4G2 re-expression rescues it, placing EIF4G2 downstream of miR-139-5p in controlling translation rates in AML. miRNA overexpression/knockdown; EIF4G2 siRNA knockdown and rescue; cell cycle analysis; xenograft mouse models Oncogene High 26165837
2015 Coxsackievirus B3 (CVB3) 2A protease (not 3C) cleaves DAP5/EIF4G2 at amino acid G434, generating 45-kDa N-terminal (DAP5-N) and 52-kDa C-terminal (DAP5-C) fragments. The N-terminal fragment translocates to the nucleus at late infection time points. DAP5-N retains ability to initiate IRES-driven translation of pro-apoptotic p53 but not pro-survival Bcl-2, and promotes CVB3 replication; DAP5-C exerts a dominant-negative effect on cap-dependent translation. Site-directed mutagenesis to identify cleavage site; overexpression of DAP5 truncation mutants; IRES reporter assays; viral replication assays; subcellular fractionation Cell death and differentiation High 26586572
2016 DAP5/EIF4G2 drives cap-independent translation of a specific subset of mRNAs in human embryonic stem cells (hESCs) that encode mitochondrial proteins involved in oxidative respiration, and this activity is required for the transition from pluripotency to differentiation. DAP5 knockdown impairs embryoid body formation, causes aberrant mitochondrial morphology and decreased oxidative respiration, and reduces translation efficiency of target mRNAs including the chromatin modifier HMGN3. siRNA knockdown in hESCs; polysome-associated RNA sequencing; mitochondrial morphology imaging; oxidative respiration assay; embryoid body formation assay Genes & development High 27664238
2012 Knockdown of Drosophila NAT1 (ortholog of EIF4G2/DAP5) in circadian pacemaker neurons lengthens circadian period and dramatically reduces PER protein levels in PDF neurons, implicating NAT1 in cap-independent translation of per mRNA. BELLE protein levels are also reduced by NAT1 knockdown, suggesting NAT1 promotes belle mRNA translation. TOR kinase inhibition increases oscillator activity in a NAT1-dependent manner, linking cap-independent translation by NAT1 to the circadian clock. Targeted RNAi knockdown in Drosophila; circadian locomotor activity assays; immunostaining for PER and BELLE proteins Genetics Medium 22904033
2021 DAP5/EIF4G2 and eIF3d form a non-canonical cap-dependent translation complex that selectively translates TGF-β-induced Treg cell differentiation and immune suppression mRNAs when mTORC1 is inhibited. This DAP5/eIF3d mechanism is directed by the 5' noncoding regions of Treg mRNAs and does not require the canonical eIF4E/mTORC1 pathway. Silencing DAP5 in naive human CD4+ T cells impairs their differentiation into Treg cells. Genome-wide transcription and translation profiling (ribosome profiling); siRNA knockdown; T cell differentiation assay; mTORC1 inhibition experiments Nature communications High 34848685
2022 EIF4G2 facilitates leaky scanning through translated upstream open reading frames (uORFs) in a subset of mammalian mRNAs. EIF4G2 promotes scanning downstream of eIF4G1-mediated 40S recruitment, replacing eIF4G1 during scanning when eIF4G1 dissociates—particularly when scanning complexes encounter translating ribosomes within a uORF. This defines EIF4G2 as a component of an 'accessory' scanning complex that rescues scanning when the principal eIF4G1-dependent complex fails. Ribosome profiling; luciferase-based reporters with uORF mutations; siRNA knockdown of EIF4G2 Nucleic acids research High 35018467
2022 DAP5/EIF4G2 is required for translation initiation on mRNAs with long, structure-prone 5' leader sequences and persistent uORF translation, particularly mRNAs encoding signaling kinases and phosphatases. DAP5-mediated translation is cap/eIF4F- and eIF4A-dependent and facilitates main CDS (but not uORF) translation, suggesting a role in translation re-initiation after uORF translation. Ribosome profiling; luciferase-based reporters with mutational analysis; siRNA knockdown of DAP5 Nature communications High 36473845
2023 DAP5/EIF4G2 and eIF3d form a cap-dependent alternative translation complex essential for breast cancer epithelial-to-mesenchymal transition (EMT), invasion, and metastasis. This complex selectively translates mRNAs encoding EMT transcription factors, cell migration integrins, metalloproteinases, and angiogenesis factors. DAP5 is not required for primary tumor growth but is essential for metastasis in human and murine breast cancer models. Genome-wide transcriptomic and translatomic profiling; DAP5 knockdown/knockout; breast cancer animal models (human and murine xenografts); migration/invasion assays Cell reports High 37314929
2024 Neuronal depolarization causes rapid phosphorylation and dendritic recruitment of EIF4G2, which then binds upstream open reading frames (uORFs) in pre-localized dendritic mRNAs to drive activity-dependent translation of downstream coding sequences involved in long-term potentiation, cell signaling, and energy metabolism. The translated uORF sequences are sufficient to confer depolarization-induced, EIF4G2-dependent translational control, establishing a uORF-based mechanism for activity-dependent local dendritic translation. Dendritically-targeted proximity labeling (APEX); crosslinking immunoprecipitation (CLIP); ribosome profiling; mass spectrometry; KCl/DHPG depolarization of primary cortical neurons; EIF4G2 knockdown Nature neuroscience High 38589584

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2006 A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 1362 16751776
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2016 ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure. Cell 1233 26777405
2004 Large-scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences of the United States of America 1159 15302935
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Molecular cell 973 22681889
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2016 An improved smaller biotin ligase for BioID proximity labeling. Molecular biology of the cell 665 26912792
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2000 Molecular genetics and epidemiology of the NAT1 and NAT2 acetylation polymorphisms. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 570 10667461
1999 Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E. The EMBO journal 538 9878069
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2003 Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nature biotechnology 485 12665801
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
1999 Cap-dependent translation initiation in eukaryotes is regulated by a molecular mimic of eIF4G. Molecular cell 426 10394359
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2014 The VCP/p97 system at a glance: connecting cellular function to disease pathogenesis. Journal of cell science 382 25146396
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2017 VCP/p97-Mediated Unfolding as a Principle in Protein Homeostasis and Signaling. Molecular cell 335 29153394
1993 Metabolic activation and deactivation of arylamine carcinogens by recombinant human NAT1 and polymorphic NAT2 acetyltransferases. Carcinogenesis 327 8353847
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2013 Covalent and allosteric inhibitors of the ATPase VCP/p97 induce cancer cell death. Nature chemical biology 315 23892893
2022 Tau interactome maps synaptic and mitochondrial processes associated with neurodegeneration. Cell 256 35063084
1997 Human eukaryotic translation initiation factor 4G (eIF4G) possesses two separate and independent binding sites for eIF4A. Molecular and cellular biology 249 9372926
2004 Functional proteomics mapping of a human signaling pathway. Genome research 247 15231748
2004 Molecular perspectives on p97-VCP: progress in understanding its structure and diverse biological functions. Journal of structural biology 246 15037236
2018 Mapping the Genetic Landscape of Human Cells. Cell 225 30033366
1995 Role of aromatic amine acetyltransferases, NAT1 and NAT2, in carcinogen-DNA adduct formation in the human urinary bladder. Cancer research 202 7585581
2019 ULK1 and ULK2 Regulate Stress Granule Disassembly Through Phosphorylation and Activation of VCP/p97. Molecular cell 151 30979586
2011 Recent advances in p97/VCP/Cdc48 cellular functions. Biochimica et biophysica acta 147 21781992
2016 Structure and function of the AAA+ ATPase p97/Cdc48p. Gene 139 26945625
2008 DAP5 promotes cap-independent translation of Bcl-2 and CDK1 to facilitate cell survival during mitosis. Molecular cell 123 18450493
2012 DVC1 (C1orf124) recruits the p97 protein segregase to sites of DNA damage. Nature structural & molecular biology 122 23042607
2008 Insights into adaptor binding to the AAA protein p97. Biochemical Society transactions 117 18208387
2017 The AAA+ ATPase p97, a cellular multitool. The Biochemical journal 115 28819009
2021 VCP/p97 regulates Beclin-1-dependent autophagy initiation. Nature chemical biology 110 33510452
2017 Toward an understanding of the Cdc48/p97 ATPase. F1000Research 108 28815021
2005 p97/p47-Mediated biogenesis of Golgi and ER. Journal of biochemistry 93 15749824
2012 Growing sphere of influence: Cdc48/p97 orchestrates ubiquitin-dependent extraction from chromatin. Trends in cell biology 87 22818974
2000 Essential role of NAT1/p97/DAP5 in embryonic differentiation and the retinoic acid pathway. The EMBO journal 87 11032820
2020 TEX264 coordinates p97- and SPRTN-mediated resolution of topoisomerase 1-DNA adducts. Nature communications 86 32152270
2016 Mutations in the Human AAA+ Chaperone p97 and Related Diseases. Frontiers in molecular biosciences 82 27990419
2008 N-acetyltransferase ARD1-NAT1 regulates neuronal dendritic development. Genes to cells : devoted to molecular & cellular mechanisms 79 19090811
2015 Inhibitors of the AAA+ chaperone p97. Molecules (Basel, Switzerland) 78 25685910
2015 DAP5 associates with eIF2β and eIF4AI to promote Internal Ribosome Entry Site driven translation. Nucleic acids research 78 25779044
2016 Ring of Change: CDC48/p97 Drives Protein Dynamics at Chromatin. Frontiers in genetics 76 27200082
2012 Expanding into new markets--VCP/p97 in endocytosis and autophagy. Journal of structural biology 74 22450227
2017 p97/VCP promotes degradation of CRBN substrate glutamine synthetase and neosubstrates. Proceedings of the National Academy of Sciences of the United States of America 73 28320958
2021 Mechanistic insight into substrate processing and allosteric inhibition of human p97. Nature structural & molecular biology 71 34262183
2013 The translation initiation factor DAP5 promotes IRES-driven translation of p53 mRNA. Oncogene 71 23318444
2007 The eIF4G homolog DAP5/p97 supports the translation of select mRNAs during endoplasmic reticulum stress. Nucleic acids research 70 18003655
1998 N-acetyltransferase NAT1 and NAT2 genotypes and lung cancer risk. Pharmacogenetics 69 9731715
2001 Relevance of N-acetyltransferase 1 and 2 (NAT1, NAT2) genetic polymorphisms in non-small cell lung cancer susceptibility. Pharmacogenetics 68 11266080
2001 Association of NAT1 and NAT2 polymorphisms to urinary bladder cancer: significantly reduced risk in subjects with NAT1*10. Cancer research 68 11431340
2003 DNA damage modulates nucleolar interaction of the Werner protein with the AAA ATPase p97/VCP. Molecular biology of the cell 67 12937274
2003 NSF and p97/VCP: similar at first, different at last. FEBS letters 67 14630332
1998 Identification of the cilium binding epitope of the Mycoplasma hyopneumoniae P97 adhesin. Infection and immunity 66 9746576
2023 Inhibitors of the ATPase p97/VCP: From basic research to clinical applications. Cell chemical biology 62 36640759
2010 The complexities of p97 function in health and disease. Molecular bioSystems 61 21152665
2011 Cdc48/p97, a key actor in the interplay between autophagy and ubiquitin/proteasome catabolic pathways. Biochimica et biophysica acta 60 21807033
2009 New ATPase regulators--p97 goes to the PUB. The international journal of biochemistry & cell biology 58 19497384
2019 Multisystem Proteinopathy Mutations in VCP/p97 Increase NPLOC4·UFD1L Binding and Substrate Processing. Structure (London, England : 1993) 57 31623962
2013 P97/CDC-48: proteostasis control in tumor cell biology. Cancer letters 57 23726843
2015 miR-139-5p controls translation in myeloid leukemia through EIF4G2. Oncogene 54 26165837
2016 Targeting p97 to Disrupt Protein Homeostasis in Cancer. Frontiers in oncology 50 27536557
1994 Structure-function studies of human arylamine N-acetyltransferases NAT1 and NAT2. Functional analysis of recombinant NAT1/NAT2 chimeras expressed in Escherichia coli. The Journal of biological chemistry 50 7929420
2023 An in vitro-transcribed circular RNA targets the mitochondrial inner membrane cardiolipin to ablate EIF4G2+/PTBP1+ pan-adenocarcinoma. Nature cancer 49 37845485
2016 Cap-independent translation by DAP5 controls cell fate decisions in human embryonic stem cells. Genes & development 49 27664238
2011 Development of p97 AAA ATPase inhibitors. Autophagy 49 21606684
2017 Suppression of EIF4G2 by miR-379 potentiates the cisplatin chemosensitivity in nonsmall cell lung cancer cells. FEBS letters 47 28117895
2012 Roles of p97-associated deubiquitinases in protein quality control at the endoplasmic reticulum. Current protein & peptide science 46 22812527
2007 The melanoma tumor antigen, melanotransferrin (p97): a 25-year hallmark--from iron metabolism to tumorigenesis. Oncogene 46 17452986
2005 Increased expression of valosin-containing protein (p97) is correlated with disease recurrence in follicular thyroid cancer. Annals of surgical oncology 46 16189643
2017 MicroRNA-379 inhibits the proliferation, migration and invasion of human osteosarcoma cells by targetting EIF4G2. Bioscience reports 45 28381518
2004 Identification of the major promoter and non-coding exons of the human arylamine N-acetyltransferase 1 gene (NAT1). Pharmacogenetics 45 15226672
2016 Nat1 Deficiency Is Associated with Mitochondrial Dysfunction and Exercise Intolerance in Mice. Cell reports 44 27705799
2021 A DAP5/eIF3d alternate mRNA translation mechanism promotes differentiation and immune suppression by human regulatory T cells. Nature communications 43 34848685
2013 Create and preserve: proteostasis in development and aging is governed by Cdc48/p97/VCP. Biochimica et biophysica acta 43 23583830
2018 Skeletal Muscle-Specific Methyltransferase METTL21C Trimethylates p97 and Regulates Autophagy-Associated Protein Breakdown. Cell reports 41 29719249
2011 Altered intracellular localization and valosin-containing protein (p97 VCP) interaction underlie ATP7A-related distal motor neuropathy. Human molecular genetics 41 22210628
2013 The p97-UFD1L-NPL4 protein complex mediates cytokine-induced IκBα proteolysis. Molecular and cellular biology 39 24248593
2020 LncRNA SDHAP1 confers paclitaxel resistance of ovarian cancer by regulating EIF4G2 expression via miR-4465. Journal of biochemistry 38 32211849
2007 Mutations in p97/VCP induce unfolding activity. FEBS letters 38 17346713
2024 Neuronal activity rapidly reprograms dendritic translation via eIF4G2:uORF binding. Nature neuroscience 36 38589584
2019 LINC01579 promotes cell proliferation by acting as a ceRNA of miR-139-5p to upregulate EIF4G2 expression in glioblastoma. Journal of cellular physiology 36 31187495
2021 MiR-144-3p-mediated dysregulation of EIF4G2 contributes to the development of hepatocellular carcinoma through the ERK pathway. Journal of experimental & clinical cancer research : CR 35 33526055
2009 Structure and function of the PLAA/Ufd3-p97/Cdc48 complex. The Journal of biological chemistry 34 19887378
2023 Breast cancer cell mesenchymal transition and metastasis directed by DAP5/eIF3d-mediated selective mRNA translation. Cell reports 33 37314929
2018 Cooperative subunit dynamics modulate p97 function. Proceedings of the National Academy of Sciences of the United States of America 33 30584095
2013 A unique IBMPFD-related P97/VCP mutation with differential binding pattern and subcellular localization. The international journal of biochemistry & cell biology 33 23333620
2021 CUL2LRR1 , TRAIP and p97 control CMG helicase disassembly in the mammalian cell cycle. EMBO reports 32 33590678
2015 Cleavage of DAP5 by coxsackievirus B3 2A protease facilitates viral replication and enhances apoptosis by altering translation of IRES-containing genes. Cell death and differentiation 32 26586572
2009 The translation initiation factor DAP5 is a regulator of cell survival during mitosis. Cell cycle (Georgetown, Tex.) 32 19158497
2023 Structural basis of ubiquitin-independent PP1 complex disassembly by p97. The EMBO journal 30 37264685
2022 Active conformation of the p97-p47 unfoldase complex. Nature communications 30 35552390
2018 The ATPase VCP/p97 functions as a disaggregase against toxic Huntingtin-exon1 aggregates. FEBS letters 30 30069866
2023 Targeting of client proteins to the VCP/p97/Cdc48 unfolding machine. Frontiers in molecular biosciences 29 36825201
2022 Ribosomal leaky scanning through a translated uORF requires eIF4G2. Nucleic acids research 29 35018467
2015 Proteasomal Degradation of Proinsulin Requires Derlin-2, HRD1 and p97. PloS one 29 26107514
2017 VCP/p97/Cdc48, A Linking of Protein Homeostasis and Cancer Therapy. Current molecular medicine 28 29521227
2016 p97 Disease Mutations Modulate Nucleotide-Induced Conformation to Alter Protein-Protein Interactions. ACS chemical biology 28 27267671
2020 Allosteric p97 Inhibitors Can Overcome Resistance to ATP-Competitive p97 Inhibitors for Potential Anticancer Therapy. ChemMedChem 27 32162487
2020 MicroRNA-6744-5p promotes anoikis in breast cancer and directly targets NAT1 enzyme. Cancer biology & medicine 26 32296579
2014 The p97-FAF1 protein complex reveals a common mode of p97 adaptor binding. The Journal of biological chemistry 25 24619421
2022 Cooperative assembly of p97 complexes involved in replication termination. Nature communications 24 36329031
2021 VPS13D interacts with VCP/p97 and negatively regulates endoplasmic reticulum-mitochondria interactions. Molecular biology of the cell 24 34133214
2017 Structure and Function of p97 and Pex1/6 Type II AAA+ Complexes. Frontiers in molecular biosciences 24 28611990
2012 NAT1/DAP5/p97 and atypical translational control in the Drosophila Circadian Oscillator. Genetics 24 22904033
2024 VCP/p97 UFMylation stabilizes BECN1 and facilitates the initiation of autophagy. Autophagy 23 38762759
2022 Multiple UBX proteins reduce the ubiquitin threshold of the mammalian p97-UFD1-NPL4 unfoldase. eLife 23 35920641
2022 DAP5 enables main ORF translation on mRNAs with structured and uORF-containing 5' leaders. Nature communications 23 36473845
2024 Characterizing ATP processing by the AAA+ protein p97 at the atomic level. Nature chemistry 22 38326645
2022 K27-linked ubiquitylation promotes p97 substrate processing and is essential for cell proliferation. The EMBO journal 22 35349166
2022 Eukaryotic translation initiation factor eIF4G2 opens novel paths for protein synthesis in development, apoptosis and cell differentiation. Cell proliferation 22 36547008
2016 Structure and functions of the chaperone-like p97/CDC48 in plants. Biochimica et biophysica acta. General subjects 22 27717811
2025 The NAT1-bHLH110-CER1/CER1L module regulates heat stress tolerance in rice. Nature genetics 21 39809898
2022 Specific mechanisms of translation initiation in higher eukaryotes: the eIF4G2 story. RNA (New York, N.Y.) 21 36517212
2021 Structural and Functional Analysis of Disease-Linked p97 ATPase Mutant Complexes. International journal of molecular sciences 21 34360842
2021 Temporal proteomics reveal specific cell cycle oncoprotein downregulation by p97/VCP inhibition. Cell chemical biology 21 34847375
2012 From neurodevelopment to neurodegeneration: the interaction of neurofibromin and valosin-containing protein/p97 in regulation of dendritic spine formation. Journal of biomedical science 21 22449146
2006 The transcripts of SFRP1,CEP63 and EIF4G2 genes are frequently downregulated in transitional cell carcinomas of the bladder. Oncology 21 16410684