EIF4E2 antibody
- Known as:
- EIF4E2 (anti-)
- Catalog number:
- orb33524
- Product Quantity:
- EUR
- Category:
- -
- Supplier:
- Biorbyt biorb
- Gene target:
- EIF4E2 antibody
Related genes to: EIF4E2 antibody
- Gene:
- EIF4E2 NIH gene
- Name:
- eukaryotic translation initiation factor 4E family member 2
- Previous symbol:
- EIF4EL3
- Synonyms:
- IF4e, 4EHP
- Chromosome:
- 2q37.1
- Locus Type:
- gene with protein product
- Date approved:
- 1999-07-22
- Date modifiied:
- 2015-08-25
Related products to: EIF4E2 antibody
Related articles to: EIF4E2 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 - mRNA translation and stability are tightly regulated and functionally linked through cis-acting sequence elements and trans-acting factors, including RNA-binding proteins (RBPs). Here, we report that two chordate-specific paralogous RBPs, ZC3H7A and ZC3H7B, preferentially bind the coding region (CDS) and 3' untranslated region (3' UTR) of A/U-rich mRNAs, particularly those with enrichment of A/U at their wobble sites (A/U3 codons). Upon binding to target mRNAs, ZC3H7A/B promote mRNA degradation through recruitment of the CCR4-NOT deadenylase complex. Furthermore, these proteins engage ribosomes lacking elongation factors and repress translation initiation via the GIGYF2/4EHP translation repressor complex. Depletion of ZC3H7A/B or 4EHP impairs the translational repression of A/U3-rich mRNAs. Together, these findings reveal a mechanism in higher eukaryotes that links A/U-rich sequence content within the CDS and 3' UTR to the coordinated post-transcriptional regulation of mRNA stability and translation. - Source: PubMed
Publication date: 2026/06/09
Harris Snell PatricNaeli ParisaGarzia AitorChen YanyuWaldron Joseph AChatterjee SusantaMcGirr TomKilmartin AidanMohammad Almomani Eman SuleimanKelsall Ian RLadak Reese JalalChoi Jung-HyunLuo JunLeino Sami AJess NaomiShariati S AliSoto XimenaGkogkas Christos GSonenberg NahumTuschl ThomasMaguire SarahJafarnejad Seyed Mehdi - Although sorafenib (SOR) is effective for advanced hepatocellular carcinoma (HCC), significant metabolic heterogeneity limits its therapeutic effect. In this study, we employed high-resolution matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) to profile the spatial lipidomic alterations in 3D HepG2 spheroids following SOR treatment. Interestingly, sphingophospholipid and glycerophospholipid metabolism played crucial roles. In an orthotopic HCC mouse model, immunohistochemical and immunofluorescence staining confirmed that SOR induced immunological and inflammatory changes. Moreover, transcriptomic and Q-PCR analyses showed increased expression of , , , , and along with decreased in the SOR treatment group compared to the tumor control group. Bio-layer interferometry and molecular docking data also indicated that ZBP1 possessed favorable binding affinities with SOR. Overall, our findings demonstrated that SOR dramatically disrupted sphingolipid metabolism in tumor cell spheroids and, in an orthotopic model, activated the NOD-like receptor signaling pathway, accompanied by altered secretion of inflammatory factors and macrophage polarization. These results suggest that SOR exerts dual effects on tumor cell lipid metabolism and the tumor immune microenvironment. These findings provide a conceptual basis for future exploration of lipid-modulating therapeutic strategies in HCC. - Source: PubMed
Publication date: 2026/05/02
Li DongshengTuo YuanyuanSai LuhengXu XiunanPeng FujuanYan ZhipengYang QinZhao HuifangZhang Ruiping - Myocardial ischemia-reperfusion injury (MIRI) involves complex molecular mechanisms. However, the roles of alternative splicing (AS) and RNA-binding proteins (RBPs) in its pathogenesis remain largely elusive. In this study, we conducted an integrated analysis of the public RNA sequencing dataset GSE214122 to identify regulated alternative splicing events (RASEs) and differentially expressed genes (DEGs) in a murine MIRI model. We identified 1262 DEGs (883 upregulated and 379 downregulated), among which 232 were RBPs. Notably, 42 RASE-related genes overlapped with the DEGs. Functional enrichment analysis revealed that aberrantly spliced genes were primarily involved in critical signaling pathways, including mechanistic target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK). Key genes identified within the mTOR pathway included Eif4e2, Atp6v1h, and Insr, while Traf6, Map4k4, and Nr4a1 were prominent in the MAPK pathway. Gene Ontology (GO) analysis further highlighted biological processes closely associated with MIRI, such as angiogenesis and cellular response to hypoxia. Co-expression network analysis demonstrated that the differentially expressed RBP LMNA was highly correlated with an alternative 5’ splice site (alt5p) event in Atp6v1h (clualt5p2389), the splicing ratio of which was significantly elevated in the MIRI group. Independent experimental validation confirmed the significant upregulation of splice isoforms for Eif4e2, Traf6, Insr, and Nr4a1. Furthermore, mRNA levels of seven RBPs (Anxa2, Fn1, Hyou1, Hif1a, Lmna, Myh9, and Stmn1) were significantly upregulated, whereas Crebrf was significantly downregulated. The Western blot results showed that the protein levels of HIF1A, FN1, LMNA, and EIF4E2 were increased in the MIRI group, while the expression of CREBRF protein was decreased. In conclusion, this study provides a systematic landscape of AS and RBP dysregulation in MIRI. We report for the first time that Lmna-regulated AS of Atp6v1h may participate in the hypoxic response and mTOR pathway modulation. These candidate RBPs and their associated AS events offer novel insights into the molecular mechanisms of MIRI and represent potential therapeutic targets. - Source: PubMed
Publication date: 2026/03/26
Zhou DanTan YingxinJiang BingLei PengNiu XiaoweiZhang Zheng - Homocysteine (Hcy) is an independent risk factor for atherosclerosis (AS). Hcy induces the transformation of vascular smooth muscle cells (VSMCs) into foam cells, which play a crucial role in this process. However, the detailed mechanism is still unclear. To identify the key regulatory proteins during this process and clarify the possible mechanism of Hcy-induced foam cell formation in VSMCs, thereby providing theoretical support for the intervention of AS. VSMCs were allocated into two groups: a control cohort and a group exposed to Hcy to simulate an AS-like state. Quantitative proteomic profiling was performed using the label-free quantitative DIA (LFQ-DIA) approach to detect differentially expressed proteins between these groups. To explore functional implications, enrichment analyses involving Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were conducted. Protein-protein interaction networks were constructed using the STRING database to identify central interactors. Target proteins were subsequently validated through parallel reaction monitoring (PRM). Furthermore, histological analyses (hematoxylin and eosin (HE) staining, Oil Red O staining), biochemical assays of lipid content (total cholesterol (TC) and triglycerides (TG)), and Western blot analysis were utilized to confirm the role and mechanism of identified proteins in the context of Hcy-driven foam cell conversion. The results showed that proteomic analysis identified 4804 proteins in total, of which 4799 passed missing-value filtering and were retained for downstream quantitative analysis. A total of 54 proteins were identified as differentially expressed using thresholds of adjusted p-value < 0.05 and fold change > 1.5. Among them, 13 proteins were upregulated, while 41 were downregulated in response to Hcy treatment. For PRM validation, 20 candidate proteins were selected according to proteomic evidence, biological relevance, and technical feasibility. Among them, 16 proteins (COX7C, STX5, UBQLN2, DDX50, TBCB, GSR, PCNP, CDV3, PEBP1, PPIA, S100A6, EIF4E2, UBQLN1, ARMC1, NUDCD2, and H1-2) showed the same direction of fold-change values as in the LFQ-DIA dataset, thereby underscoring the reliability of the proteomic analysis. Data are available via ProteomeXchange with identifier PXD064315. Histological staining demonstrated enhanced lipid accumulation, and the protein expression of the contraction phenotype marker a-SMA decreased, while the protein expression of the synthesis phenotype marker OPN increased. This indicates that Hcy induces VSMCs to transform from a contraction phenotype to a synthesis phenotype, resulting in the formation of foam cells. The protein levels of COX7C and sterol regulatory element-binding proteins (SREBP1C and SREBP2) were elevated upon Hcy exposure. Overexpression of COX7C further augmented the expression of SREBP1C and SREBP2, exacerbated lipid accumulation, and promoted foam cell transformation in Hcy-treated VSMCs. On the other hand, knockdown of COX7C had the opposite effect. Overall, the results of the present study suggest that COX7C plays a crucial regulatory role in Hcy-induced transformation of VSMCs into foam cells. Its pathogenic role is likely mediated through the upregulation of SREBP1C and SREBP2, thereby promoting lipid accumulation. These findings provide new insights into AS pathogenesis and identify COX7C maybe a potential therapeutic target. - Source: PubMed
Publication date: 2026/02/05
Wang XiuyuMa XinpengZhang XiangMa XingZhang Minghao