Ask about this productRelated genes to: EIF4G2 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: EIF4G2 antibody
Related articles to: EIF4G2 antibody
- 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 - CD8 T cell lineage commitment in the thymus requires interleukin-7 receptor (IL-7R) signaling, but the mechanisms enabling its cytokine responsiveness are unclear. Here, we identify the translation factor eIF4G2 as an essential, selective regulator of this process. eIF4G2 expression is upregulated in double-positive thymocytes and its T cell specific deletion causes a severe post-selection blockade, specifically abolishing CD8 single positive thymocyte lineage commitment while sparing CD4 lineage choice and TCR signaling. Mechanistically, eIF4G2 deficiency ablates IL-7 responsiveness by failing to sustain the receptor γc subunit via an untranslated region dependent manner, with a concomitant impairment of IL-7Rα mRNA level. Our findings establish eIF4G2 as a pivotal translational checkpoint that licenses IL-7R signaling to enforce faithful CD8 T cell fate determination. - Source: PubMed
Publication date: 2026/03/11
Cui JialongZhang XinhuiYang YangShan LidongLi YangJiang LongXie WeiJin TengchuanLang Xueting - Pancreatic ductal adenocarcinoma (PDA) is among the most lethal cancers, driven by cellular plasticity that fuels therapeutic resistance and early dissemination. The contribution of translational control to this plasticity remains poorly understood. Through an CRISPR/Cas9 screen, we identify the non-canonical initiation factor eIF4G2 (DAP5/NAT1) as a translational checkpoint restraining PDA progression. Loss of eIF4G2 accelerated tumor growth, induced poorly differentiated, basal-like histology, and triggered widespread metastasis. Ribosome profiling revealed that eIF4G2 loss does not alter bulk protein synthesis but instead impairs translation of a selective regulon, including tumor suppressors such as PTEN and CREBBP. Functional studies confirmed that PTEN loss was sufficient to drive dedifferentiation but insufficient to promote metastasis, implicating the broader eIF4G2-dependent program, including translational control of transcriptional regulators like CREBBP, in limiting dissemination. Consistently, eIF4G2-deficient tumors exhibited transcriptomic enrichment of programs related to migration and wound healing. Computational inference from human PDA datasets revealed reduced eIF4G2 activity in metastases, aligning with basal-like features and predicting poorer survival. These results support a model in which eIF4G2 maintains epithelial identity and restrains metastatic potential, highlighting selective translation as a determinant of PDA subtype and clinical outcome. - Source: PubMed
Publication date: 2026/03/17
Powers JustinLai WeiKobayashi HirokiCuriel-Garcia AlvaroAhmadi PardisValenzuela ElizabethJovanovic MarkoChavez AlejandroChio Iok In Christine - Regulation of mRNA translation is essential for cellular homeostasis, and its dysregulation contributes to cancer, neurodegeneration, and developmental disorders. Stress granules are cytosolic condensates that form during stress-induced translation arrest and are enriched in mRNAs, translation factors, and RNA-binding proteins, but how stress granule proteins modulate translation remains poorly understood. Here, we identify the stress granule components Proline-Rich Coiled-Coil A, B, and C (PRRC2 proteins) as translation regulators. PRRC2 proteins are large, intrinsically disordered paralogs conserved across jawed vertebrates. Functional proteomics revealed that all PRRC2 proteins associate with the 48S translation initiation complex (PIC), whereas PRRC2B additionally interacts with nuclear proteins. Under stress, the proximal interaction network of PRRC2 proteins undergoes dynamic remodeling, including increased interactions with the stress granule scaffold G3BP1. Genetic perturbation shows that the PRRC2 proteins influence stress granule assembly in a context-specific manner, and are collectively required for cell growth in basal conditions due to their essential role in translation. Cells with reduced PRRC2 proteins exhibit a significant reduction in the abundance of more than half of the proteome, with a bias toward translational targets of eIF3d and eIF4G2. Interaction domain mapping and AlphaFold3 modeling revealed that an α helix within the putative coiled-coil domain of PRRC2C mediates interactions with the eIF3 core complex. This modeling places the PRRC2C α helix in a previously unassigned region of a published cryo-EM density map, validating the protein interaction and the mechanistic role of PRRC2C in translation control. Together, these findings establish PRRC2 proteins as components of the translation initiation machinery that regulate translation through their interactions with the eIF3 complex and other components of the 48S PIC factors, providing a direct mechanistic link between stress granule proteins and translational control. - Source: PubMed
Publication date: 2026/02/25
Huang Jie QiKadijk EileighSchreiber Karl JLiu Zi HaoChiang Rachel WZhang ZhixinGuttman KevinHuang Tian HaoAlmeida Sylvia M TZhulyn OlenaMoses AlanForman-Kay Julie DRubinstein John LYoun Ji-Young - African swine fever virus (ASFV) is a highly contagious and lethal double-stranded DNA virus that relies on host cellular translation machinery for replication and immune evasion. The multigene family 110 (MGF110) contains several members with incompletely defined functions. Here, the role of MGF110-7L in host translation regulation was investigated in HEK-293T and PK15 cells. Ribopuromycylation assays demonstrated that MGF110-7L expression resulted in potent, dose- and time-dependent inhibition of nascent polypeptide synthesis. Western blotting revealed a selective reduction in eIF4G1 protein abundance, with no significant changes in eIF4G2, eIF4E, and eIF4A, while eIF4G1 mRNA levels remained unaffected, indicating post-transcriptional regulation. Overexpression of eIF4G1 partially rescued translation suppression. MGF110-7L also decreased eIF4B phosphorylation and activated the PERK/eIF2α pathway, consistent with the induction of endoplasmic reticulum (ER) stress. ER stress promoted stress granule (SG) formation and enhanced eIF4G1 association with the SG marker G3BP1. The inhibitor assays demonstrated that the suppression of eIF2α phosphorylation by ISRIB restored the abundance of eIF4G1 protein. In addition, the downregulation of eIF4G1 was reversed by the inhibition of autophagy using bafilomycin A1, indicating an SG-linked autophagy-lysosome degradation pathway. Co-immunoprecipitation assays confirmed increased eIF4G1-G3BP1 interaction, but no direct binding between MGF110-7L and eIF4G1. This work provides the first experimental evidence that an ASFV protein, MGF110-7L, suppresses cap-dependent translation through SG-mediated autophagic degradation of eIF4G1, thereby revealing a previously unrecognized mechanism of ASFV translational control. These findings not only extend current understanding of ASFV-host interactions but also suggest potential molecular targets for antiviral strategies and rational vaccine design. - Source: PubMed
Publication date: 2026/02/12
Gao XinyuJiang SuduoZhang LiyanGao ZhenqiuXiao LijieCao Hongwei