DHFRL1 Blocking Peptide
- Known as:
- DHFRL1 Blocking Peptide
- Catalog number:
- 33r-7973
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Fitzgerald industries international
- Gene target:
- DHFRL1 Blocking Peptide
Related genes to: DHFRL1 Blocking Peptide
- Gene:
- DHFR2 NIH gene
- Name:
- dihydrofolate reductase 2
- Previous symbol:
- DHFRP4, DHFRL1
- Synonyms:
- FLJ16119
- Chromosome:
- 3q11.2
- Locus Type:
- gene with protein product
- Date approved:
- 2005-02-07
- Date modifiied:
- 2017-11-28
Related products to: DHFRL1 Blocking Peptide
Related articles to: DHFRL1 Blocking Peptide
- T-cell engagers (TCEs) show promise in cancer immunotherapy but face challenges in solid tumors due to heterogeneity, antigen escape, and limited T-cell infiltration. To address this, we developed a modular platform using chemically self-assembled nanorings (CSANs). We engineered a bifunctional fusion protein, E1-DHFR2-αCD3, with an EGFR-binding fibronectin (E1) and an anti-CD3 scFv on a DHFR2 scaffold. With bis-methotrexate, the monomers formed multivalent cis-CSANs. Both monomers and CSANs bound EGFR+ tumor cells and T-cells, were internalized, and induced dose-dependent, EGFR- and T-cell-dependent cytotoxicity in co-culture assays. The system was reproducible across T-cell donors. To expand targeting, E1-DHFR2-αCD3 co-assembled with other DHFR2 monomers targeting GFP or EpCAM, forming trispecific CSANs capable of binding multiple antigens and mediating cytotoxicity. This platform enables the discovery of potent multispecific TCEs to address antigen escape and solid tumor heterogeneity. Future work will focus on optimizing antigen combinations to enhance efficacy across breast cancer subtypes. - Source: PubMed
Publication date: 2025/08/01
Dahlberg DeclanMcKnight BrandiKulkarni AbhishekRozumalski LakmalRodriguez FreddysWang YiaoWagner Carston R - Dihydrofolate reductase activity is required in One Carbon Metabolism to ensure that the biologically active form of folate, tetrahydrofolate, is replenished and available as an enzyme cofactor for numerous cellular reactions, including purine and pyrimidine synthesis. Most cellular enzyme activity was thought to arise from the product of the DHFR gene on chromosome 5, with its paralogue DHFR2 (formerly known as DHFRL1; [chromosome 3]), believed to be responsible for mitochondrial dihydrofolate activity based on recombinant versions of the enzyme. In this paper, we confirm our earlier findings that dihydrofolate reductase activity in mitochondria is derived from the DHFR gene rather than DHFR2 and that endogenous DHFR2 protein is not detectable in most cells and tissues. Using HepG2 cell lines with modulated expression of either DHFR or DHFR2, we observed an impact of DHFR2 RNA on One Carbon Metabolism mediated through an influence on DHFR expression and activity. Knockout of DHFR2 results in a drop in dihydrofolate reductase activity, lowered 10-formyltetrahydrofolate abundance, downregulation of DHFR mRNA, and diminished DHFR protein abundance. We also observed downregulation of Serine Hydroxymethyltransferase and Thymidylate Synthase, two One Carbon Metabolism enzymes that work with DHFR to support de novo thymidylate synthesis. The expression of recombinant DHFR2 resulted in restoration of DHFR mRNA and protein levels while a DHFR knockdown cell line showed upregulation of DHFR2 RNA. We propose that the DHFR2 gene encodes an RNA molecule that regulates cellular dihydrofolate reductase activity through its impact on DHFR mRNA and protein. - Source: PubMed
Drago PaolaBookey NiamhLeung Kit-YiHenry MichaelMeleady PaulaGreene Nicholas D EParle-McDermott Anne - Ischemic stroke (IS) is a leading cause of death and disability worldwide. Screening for marker genes in IS is crucial for its early diagnosis and improvement in clinical outcomes. In the study, the gene expression profiles in the GSE22255 and GSE37587 datasets were extracted from the public database Gene Expression Omnibus. Weighted gene co‑expression network analysis (WGCNA) was used to investigate the gene sets that were related to ubiquitination. A total of 33 ubiquitination-related differentially expressed genes (DEGs) were identified using "limma (version 3.50.0)". Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) analysis enriched multiple pathways that were closely related to IS. The correlations between the HALLMARK signaling pathways and DGEs were analyzed. Receiver operating characteristic analysis was used to validate the diagnostic value of the key genes. Among them, 16 genes were identified as hub genes. Single-sample GSEA was performed to evaluate the infiltration status of immune cells in IS. To understand the potential molecular mechanisms of the hub genes in IS, we constructed RBP-mRNA and mRNA-miRNA-lncRNA interaction networks. Additionally, we used the GeneMANIA database to create a PPI network for the signature genes to investigate their functions. As a result, there was a significant difference in the overall infiltration of immune cells between the IS and control groups. Among the 28 types of immune cells, the degree of infiltration of seven types was significantly different between the two groups (p<0.05). The expression of four types of immune cells, namely type 1 T helper cell, type 17 T helper cell, eosinophil, and mast cell, in the IS group were significantly higher than that in the control group. The expressions of DHFR2 (R = -0.575; p<0.001) and DNAAF2 (R = -0.562; p<0.001) were significantly negatively correlated with eosinophil infiltration. The PPI network demonstrated that the 16 hub genes interacted with each other. In conclusion, we identified DEGs, WGCNA modules, hub genes, enriched pathways, and infiltrating immune cells that may be closely involved in IS. Further studies are required to explore the functions of these genes. - Source: PubMed
Publication date: 2024/12/05
Zhang ZongyongZheng ZongqingLuo WenweiLi JieboLiao JiushanChen FuxiangWang DengliangLin Yuanxiang - A functional role has been ascribed to the human dihydrofolate reductase 2 (DHFR2) gene based on the enzymatic activity of recombinant versions of the predicted translated protein. However, the in vivo function is still unclear. The high amino acid sequence identity (92%) between DHFR2 and its parental homolog, DHFR, makes analysis of the endogenous protein challenging. This paper describes a targeted mass spectrometry proteomics approach in several human cell lines and tissue types to identify DHFR2-specific peptides as evidence of its translation. We show definitive evidence that the DHFR2 activity in the mitochondria is in fact mediated by DHFR, and not DHFR2. Analysis of Ribo-seq data and an experimental assessment of ribosome association using a sucrose cushion showed that the two main Ensembl annotated mRNA isoforms of DHFR2, 201 and 202, are differentially associated with the ribosome. This indicates a functional role at both the RNA and protein level. However, we were unable to detect DHFR2 protein at a detectable level in most cell types examined despite various RNA isoforms of DHFR2 being relatively abundant. We did detect a DHFR2-specific peptide in embryonic heart, indicating that the protein may have a specific role during embryogenesis. We propose that the main functionality of the DHFR2 gene in adult cells is likely to arise at the RNA level. - Source: PubMed
Publication date: 2024/01/14
Bookey NiamhDrago PaolaLeung Kit-YiHughes LindaMacCooey AoifeOzaki MariHenry MichaelDe Castro Sandra C PDoykov IvanHeywood Wendy EMills KevinMurphy Michelle MCavallé-Busquets PereCampbell SusanBurtenshaw DeniseMeleady PaulaCahill Paul AGreene Nicholas D EParle-McDermott Anne - The effect of exogenous salicylic acid (SA) on folate metabolism and the related gene regulatory mechanisms is still unclear. In this study, the panicle of foxtail millet treated with different SA concentrations showed that 6 mM SA doubled the 5-methyltetrahydrofolate content compared to that of the control. An untargeted metabolomic analysis revealed that 275 metabolites were enriched in amino acid metabolic pathways. Significantly, the relative content of methionine (Met) after 6 mM SA treatment was 3.14 times higher than the control. Transcriptome analysis revealed that differentially expressed genes were mainly enriched in the folate and amino acid biosynthesis pathways (including Met, Cys, Pro, Ser et al.). The miRNA-mRNA interactions related to the folate and Met metabolic pathways were analyzed and several likely structural gene targets for miRNAs were identified, miRNA-seq analysis revealed that 33 and 51 miRNAs targeted 11 and 15 genes related to the folate and Met pathways, respectively. Eight key genes in the folate metabolism pathway were likely to be up-regulated by 14 new miRNAs and 20 new miRNAs up-regulated the 9 key genes in the Met metabolism pathway. The 6 miRNA-mRNA interactions related to the folate and Met metabolism pathways were verified by qRT-PCR, and consistent with the prediction. The results showed that gene expression level related to folate synthesis was directly up-regulated by Nov-m0139-3p with 3.8 times, but was down-regulated by Nov-m0731-5p with 0.62 times. The expression level of and related to Met synthesis were up-regulated by Nov-m0461-5p and Nov-m0664-3p with 4.27 and 1.32 times, respectively. Our results suggested that exogenous SA could induce the folate and Met accumulated in the panicle of foxtail millet. The higher expression level of , , and in the folate and Met metabolism pathway and their regulators, including Nov-m0139-3p, Nov-m0717-5p, Nov-m0461-5p and Nov-m0664-3p, could be responsible for these metabolites accumulation. This study lays the theoretical foundation for elucidating the post-transcription regulatory mechanisms of folate and Met metabolism. - Source: PubMed
Publication date: 2022/12/06
Hou SiyuMen YihanZhang YijuanZhao KaiMa GuifangLi HongyingHan YuanhuaiSun Zhaoxia