Ask about this productRelated genes to: EIF4E2 Blocking Peptide
- 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 Blocking Peptide
Related articles to: EIF4E2 Blocking Peptide
- 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 - Tumour-associated macrophages (TAMs) play a pivotal role in shaping the immune microenvironment of hepatocellular carcinoma (HCC), influencing tumour progression and immunotherapy response. WDR4, a tRNA-binding cofactor of the N-methylguanosine (mG) methyltransferase complex, remains poorly understood in its independent functions. Here we show that WDR4 is significantly upregulated in HCC-associated TAMs and correlates with poor prognosis. Loss of WDR4 in monocyte-derived macrophages, but not in resident Kupffer cells, reprogrammes TAMs towards an antitumoral phenotype and suppresses HCC progression. Mechanistically, cytoplasmic WDR4 acts independently of mG modification by directly interacting with eIF4E2 to enhance eIF4E-mediated selective translation of ABCA1, thereby promoting membrane cholesterol efflux and maintaining pro-tumoral polarization. Targeted silencing of WDR4 in TAMs using a CpG-small interfering RNA delivery system enhances antitumour immunity, inhibits tumour progression and improves the efficacy of anti-PD-1 therapy. Our findings identify WDR4 as a key regulator of TAM polarization and a promising therapeutic target to enhance immunotherapeutic outcomes. - Source: PubMed
Publication date: 2025/11/28
Liu JieQu ChengmingLiu YingyiGongye XiangdongZhang MingheMa TianyinHe WenzhiWang HaitaoChen XiXia PengYuan Yufeng - Eukaryotic translation initiation factor 4E family member 2 (eIF4E2) has recently been identified as an interacting protein of GSK3β and regulates its proline-directed kinase activity. eIF4E2 undergoes ISGylation at K134 and K222, a conserved posttranslational modification mediated by interferon-stimulated gene 15. In this study, we engineered a novel Nanobody-based ISGylation Targeting Chimera (NITAC) tool to specifically activate eIF4E2 ISGylation and investigate its role in the eIF4E2-GSK3β signaling pathway. By integrating eIF4E2-specific nanobodies Nb.30C7 with the catalytic E3 ligase domain HECT from HERC5, we constructed the NITAC (Nb.30C7-HECT). This NITAC tool mediates site-specific ISGylation of eIF4E2, enhancing the eIF4E2-GSK3β interaction and unexpectedly suppressing proline-directed serine/threonine phosphorylation across multiple crucial targets within the eIF4E2-GSK3β pathway. Importantly, NITAC treatment exerted cytoprotection against oxygen-glucose deprivation/reoxygenation stress, a commonly used in vitro model to simulate ischemic conditions in cell cultures. Furthermore, NITAC treatment reduced reactive oxygen species in neurons and microglia and promoted an anti-inflammatory phenotype in microglia by suppressing proline-directed serine/threonine phosphorylation. In summary, we created a novel NITAC to specifically activate eIF4E2 ISGylation, which showed cytoprotective effects under oxygen-glucose deprivation/reoxygenation stress by inhibiting GSK3β proline-directed kinase activity. - Source: PubMed
Publication date: 2025/09/27
Li LanGong JinjinLiang HuitingYang YingWu YuanshunYin ZiyiWang AnniLuo ShaoxiangChen JianZhang Min - Ammonia stress is a severe environmental problem in shrimp aquaculture, causing oxidative damage, immune suppression, and metabolic disturbance. Puerarin is a bioactive flavonoid possessing antioxidant, anti-inflammatory, antibacterial, and immunomodulatory properties. This study examines puerarin supplementation's impact on immune response, growth performance, oxidative defense system, and ammonia metabolism in Litopenaeus vannamei under ammonia-induced stress. For 56 days, shrimp (designated as groups p0, p15, p30, p60, and p120, respectively) were fed diets supplemented with puerarin at 0, 15, 30, 60, and 120 mg/kg, followed by a 48h acute ammonia challenge. The findings indicated that dietary puerarin significantly improved feed utilization, growth, and survival rates. Analysis of enzyme activity revealed that treatment groups p30, p60, and p120 had higher levels of trypsin (TPS) and amylase (AMS) activity (P < 0.05). After 56 days, acid phosphatase (ACP) and alkaline phosphatase (AKP) activities were significantly increased in all treated groups (P < 0.05), with the highest levels observed in the p60 group. A similar trend was observed following ammonia stress. After 56 days, shrimp exhibited elevated antioxidant enzyme activity, superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) levels rising significantly (P < 0.05), and a significant decline in malondialdehyde (MDA) content (P < 0.05), suggesting improved ability to cope with oxidative stress. p30, p60, and p120 groups showed increased gene expression of target of rapamycin (tor), eukaryotic translation initiation factor 4E1a (eif4e1a, eif4e2, and eif4ebp) (P < 0.05). After the ammonia stress challenge, antioxidant indicators (SOD, T-AOC, CAT, and MDA) exhibited trends consistent with those observed at the feeding trial's conclusion. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase (SOD), glutamine synthetase (GS) and glutamate dehydrogenase (GDH) genes were significantly upregulated in p30, p60, and p120 groups compared to p0 (P < 0.05), while heat shock protein 70 (HSP70), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β) were significantly downregulated within these groups relative to p0 (P < 0.05). The catalase (CAT) gene showed its lowest expression in the p30 group (P < 0.05), whereas no significant differences were found among the other treatments (P > 0.05). The findings indicate that puerarin increases L. vannamei growth, digestive utilization, and immunological capacity under ammonia stress, indicating its potential as a functional feed addition. A dietary inclusion level of 30 mg/kg was shown to be optimal. - Source: PubMed
Publication date: 2025/07/09
Chang Yu-LinQi LongGuan Chao-LiHe Yu-YunLu Wen-XingZhong Guo-Fang - Hypoxia is a common characteristic of the tumor microenvironment leading to aggressive phenotypes. A major response to hypoxia is through the induction of gene programs by the hypoxia-inducible factors (HIF). Previously, we showed that the DEAD-box RNA helicase DDX28 negatively regulates hypoxic eIF4E2-directed translation through its interaction with HIF-2α. We hypothesized that DDX28 is a tumor suppressor that represses the oncogenic HIF-2α axis. Here, we overexpress DDX28 in MDA-MB-231 breast cancer and U87MG glioblastoma cells that have very low and normal endogenous levels of DDX28, respectively, compared with noncancerous HEK293. We show that DDX28 suppresses cell migration, spheroid growth, and invasion in MDA-MB-231, but not U87MG cells. However, suppression is not through the HIF-2α gene program, but through DDX28 impacting cellular bioenergetics. DDX28 levels altered how cells utilized mitochondrial respiration and glycolysis for ATP generation. Furthermore, the pharmacological inhibition of these processes specifically reversed the effects of DDX28 overexpression. This study shows that low endogenous DDX28 levels promote hypoxic migration, and growth/invasion in three-dimensional structures in cells that have a bioenergetic profile that favors glycolysis such as MDA-MB-231. - Source: PubMed
Publication date: 2025/06/25
Bebenek OliviaPascetta Sydney ASteed JoshuaMizzoni MorganKellington Alexandria TBarnes Margaret KOsorio-MacCready TessUniacke James