Ask about this productRelated genes to: DAP5 antibody
- Gene:
- EIF4G2 NIH gene
- Name:
- eukaryotic translation initiation factor 4 gamma 2
- Previous symbol:
- -
- Synonyms:
- DAP5, NAT1, p97
- Chromosome:
- 11p15.4
- Locus Type:
- gene with protein product
- Date approved:
- 1998-02-17
- Date modifiied:
- 2016-10-05
Related products to: DAP5 antibody
Related articles to: DAP5 antibody
- Therapeutic resistance to DNA-damaging agents (DDAs) remains a primary obstacle in non-small cell lung cancer (NSCLC) treatment. Through multi-level analyses of clinical cohorts, cell lines, and derived resistant models, we identify eIF4E2 as a promising predictor of resistance to diverse DDAs. Using cisplatin as a model DDA, we find that eIF4E2 deficiency enhances DNA repair and promotes chemoresistance. Mechanistically, eIF4E2 represses translation of the DNA repair helicase WRN by recruiting the miRISC/CCR4-NOT complex to its 3'UTR via hsa-miR-130b-3p/301b-3p. Loss of eIF4E2 relieves WRN translation repression, potentiating DNA repair and attenuating DDA-induced DNA damage. Furthermore, combining the WRN inhibitor HRO761 with cisplatin enhances cytotoxicity in cisplatin-resistant cells. Collectively, these results establish that low eIF4E2 and high WRN levels predict chemoresistance, and that targeting WRN is a promising strategy to overcome cisplatin resistance in NSCLC. - Source: PubMed
Publication date: 2026/07/13
Lin XianrongZhang RuiTao WenjunWu YuxinHuang YifeiLi GuozhiSun JiajuZhang JunLiu Xiao-MinZhou Jun - In mammalian cells, pre-mRNA splicing requires the excision of multiple introns within the same nascent transcript through the coordinated action of the spliceosome and accessory factors. We and others recently demonstrated that multi-intron splicing follows a predetermined order, and that removal of proximal introns is coordinated. Notably, specific introns that are removed later within a transcript depend on their neighboring introns for efficient excision, but the underlying mechanisms remain unknown. Here, we investigated the determinants of splicing order and coordination using a multi-intron minigene splicing reporter based on the human gene EIF4G2. We found that dependency between a later-excised intron and its neighbor is partially mediated through the downstream 5' splice site, consistent with the exon definition model, but is independent from intron length. Importantly, splicing coordination also relies on a prior downstream act of splicing, but not on specific cis regulatory elements in neighboring introns. Together, these findings improve our understanding of how distinct splicing reactions are connected and coordinated to produce mature RNA molecules. - Source: PubMed
Publication date: 2026/06/27
Pelletier Marie-LeeVincent JoëlleMalo TéaSéguin CamilleTsybulskyi VolodymyrSemenchenko EgorSoumana Adamou IbrahimMeyer Irmtraud MChoquet Karine - RNA modifications have emerged as central regulators of cancer translational control. Unlike transcriptional reprogramming, which unfolds over hours, modification-dependent translational rewiring enables rapid proteomic adaptation to the nutrient-deprived, hypoxic, and immunologically hostile tumour microenvironment. Yet most existing reviews organize epitranscriptomic mechanisms by modification type or cancer hallmark, obscuring the mechanistic logic by which chemical marks collectively reshape the translational apparatus. This review adopts a translation-centric framework, examining how the most abundant modifications on mRNAs, tRNAs, and rRNAs regulate each stage of protein synthesis in malignant cells. We survey the epitranscriptomic toolkit, including modification chemistries, enzymatic writers, readers, and erasers, and detection technologies including nanopore direct RNA sequencing. We then trace how modifications control initiation (m6A-driven mRNA circularization, cap-independent translation eIF3 and eIF4G2, rRNA 2'-O-methylation-directed cap-to-IRES switching), elongation (m6A-induced ribosome stalling coupled to mRNA decay, tRNA mcm5s2U-mediated codon-biased translation, YTHDF1-dependent elongation factor recruitment), and termination (pseudouridine-mediated stop codon readthrough, NMD evasion). Crucially, we show that mRNA, tRNA, and rRNA modifications do not act in isolation but form integrated networks. For example, mRNA m6A and tRNA mcm5s2U operate on opposing arms of the same regulatory axis, with direct implications for therapeutic design. We assess the expanding drug pipeline, from the METTL3 inhibitor STC-15 now in Phase 1b/2 trials and METTL3-targeting PROTACs to FTO and ADAR1 inhibitors, and argue that biology-informed combination strategies targeting multiple modification axes will be essential for durable clinical responses. - Source: PubMed
Publication date: 2026/07/01
Joy MerinCleynen AliceShirokikh Nikolay E - The lethality of pancreatic ductal adenocarcinoma (PDAC) is driven, in part, by cellular plasticity that facilitates dedifferentiation and dissemination. Although transcriptional programs underlying these processes are well characterized, the contribution of translational control to PDAC cell-state regulation in vivo needs to be further understood to develop strategies to restrain malignant plasticity. Using a genome-wide CRISPR/Cas9 screen in immunocompetent hosts, we identified the noncanonical initiation factor eIF4G2 (DAP5/NAT1) as a translational checkpoint that restrains PDAC progression. Loss of eIF4G2 accelerated tumor growth, promoted poorly differentiated, basal-like histology, and triggered widespread metastasis. Ribosome profiling revealed that eIF4G2 supports the translation of a discrete cohort of mRNAs with long, guanine-cytosine (GC)-rich, structured 5' untranslated regions, including tumor suppressors such as Pten and transcriptional regulators such as Crebbp. Accordingly, loss of eIF4G2 was accompanied by secondary transcriptional enrichment of migration and wound-healing programs and induction of basal-like markers. In human PDAC, eIF4G2 expression was reduced in poorly differentiated lesions, and functional eIF4G2 perturbation in patient-derived PDAC cells increased clonogenic growth, whereas enforced eIF4G2 expression suppressed colony formation. Computational inference from human PDAC datasets revealed that reduced eIF4G2 activity correlated with increased metastasis, enhanced basal-like features, and poorer patient survival. Together, these findings establish noncanonical translation initiation as a determinant of PDAC cell-state control and identify eIF4G2 as a barrier to malignant plasticity and metastatic dissemination. - Source: PubMed
Powers JustinWei LaiCheung Justin Chak TingAhmadi PardisKobayashi HirokiCuriel-Garcia AlvaroKang StellaValenzuela ElizabethJovanovic MarkoChavez AlejandroChio Iok In Christine - eIF4G2 (DAP5/NAT1) is a non-canonical translation initiation factor, but its role in homeostasis is unclear. Using inducible Eif4g2 knockout mice and intestinal organoids, we show that eIF4G2 loss collapses Lgr5 intestinal stem cell (ISC) and secretory maturation programs while preserving villus architecture. Transcriptomic and single-nucleus multiome analyses reveal a durable fetal-like/regenerative state with YAP-TEAD activation and regenerative absorptive cells. Ribosome profiling identifies selective translation-efficiency loss among chromatin regulators, especially the KAT3 coactivators CREBBP and EP300, resulting in reduced KAT3 abundance and global histone acetylation; chemical KAT3 inhibition phenocopies this state. CUT&Tag and assay for transposase-accessible chromatin sequencing (ATAC-seq) demonstrate that reduced eIF4G2-KAT3 output drives locus-selective enhancer remodeling, with loss of adult ISC/Wnt-Notch elements and activation of TEAD-enriched fetal loci, without inflammatory or integrated stress response programs driving the transition. Fetal intestinal spheroids remain viable despite similar biochemical defects, highlighting a stage-specific requirement for translational buffering in maintaining adult identity. - Source: PubMed
Publication date: 2026/04/30
Kunitomi HarukoKhaine Aye MyatJamee RadiaArreola VanessaLancero MariselleRaychaudhuri AmbaPerli SamuelSato YoshikoIwasaki MioRuivo PedroTomoda KiichiroMito MariShichino YuichiIwasaki ShintaroYamanaka Shinya