Ask about this productRelated genes to: GFPT2 Blocking Peptide
- Gene:
- GFPT2 NIH gene
- Name:
- glutamine-fructose-6-phosphate transaminase 2
- Previous symbol:
- -
- Synonyms:
- GFAT2
- Chromosome:
- 5q35.3
- Locus Type:
- gene with protein product
- Date approved:
- 1999-05-06
- Date modifiied:
- 2016-10-05
Related products to: GFPT2 Blocking Peptide
Related articles to: GFPT2 Blocking Peptide
- Glutamine-fructose-6-phosphate amidotransferase 2 (GFPT2) is a rate-limiting enzyme of the hexosamine biosynthetic pathway, but its protein-level expression and functional relevance in lung adenocarcinoma (LUAD) remain unclear. - Source: PubMed
Publication date: 2026/06/06
Wang ZixuFu JiangTang ShengjieQiu GangTang ShoujunLiu TaoHu HaiyangGuo HaiyangYang LiZhou Haining - Non-small cell lung carcinoma (NSCLC) remains a leading cause of cancer-related mortality worldwide, with existing therapies frequently hindered by drug resistance and immunosuppression. Metabolic reprogramming (glycolysis, lipid metabolism, and amino acid metabolism) has emerged as a core hallmark driving NSCLC progression, tumor microenvironment (TME) remodeling, and treatment failure, transcending the classical Warburg effect to involve intricate cross-talk between cancer cells and stromal components. - Source: PubMed
Publication date: 2026/04/15
Liu JiajunQian Fenhong - BACKGROUND: Atherosclerosis (AS) is a chronic inflammatory disease characterized by lipid-laden macrophage foam cell formation and defective efferocytosis. This study aims to investigate the impact of GFPT2 on macrophage function in AS and its underlying mechanisms. METHODS: We established an AS model using high-fat diet-fed ApoE−/− mice and ox-LDL-treated RAW264.7 and bone marrow-derived macrophages. H&E staining was conducted to examine histopathological changes in the abdominal aorta. Foam cell formation was evaluated by Oil-red-O staining and Dil-ox-LDL uptake, while efferocytosis was measured using apoptotic thymocyte clearance assays. Protein glycosylation was analyzed via PNGase F digestion and site-directed mutagenesis. GFPT2 knockdown and overexpression were performed to assess its functional role. RESULTS: GFPT2 was upregulated in abdominal aortic tissues and peritoneal macrophages from AS mice, as well as ox-LDL-treated macrophages. In vitro, GFPT2 knockdown reduced foam cell formation, enhanced macrophage efferocytosis, suppressed pro-inflammatory responses, and attenuated mitochondrial ROS production. Notably, GFPT2 downregulated ACADL and Arg1 expression by promoting ACADL N-glycosylation. Moreover, GFPT2 disrupted macrophage function in AS models through regulating Arg1. ACADL knockdown suppressed GFPT2 knockdown-improved macrophage function in AS models. Furthermore, GFPT2 knockdown attenuated the ox-LDL-induced activation of NF-κB and STAT2 and suppression of PPARγ expression. In vivo, GFPT2 knockdown improved serum lipid profile, ameliorated plaque burden, enhanced macrophage efferocytosis, and reduced systemic inflammation in AS mice. CONCLUSION: Our findings revealed a novel GFPT2-ACADL-Arg1 regulatory axis in AS, where GFPT2 suppressed Arg1 expression via promoting ACADL glycosylation, thereby promoting foam cell formation, impairing efferocytosis, and exacerbating inflammation. Moreover, GFPT2 regulated key transcriptional regulators (NF‑κB, STAT2, PPARγ). These results identified GFPT2 as a pivotal regulator of macrophage homeostasis in AS. - Source: PubMed
Publication date: 2026/04/14
Ke KunYan LeyeChen RongZhang ChuanrongYang WeizhuZhang ZefuLin Junqing - CD34 has long been defined as a canonical marker for endothelial progenitors as well as hematopoietic stem cells, implicating its role in vascular development and hematopoiesis. However, the precise developmental hierarchy and lineage potential of CD34 cells remain controversial. In this study, we integrated inducible genetic lineage tracing techniques, proteomics and single-cell RNA-seq (scRNA-seq) analyses to elucidate the dynamic developmental trajectory of CD34 cells during various embryonic periods in both humans and mice. Remarkably, our analyses indicated that the progeny of CD34 cells marked distinct, spatiotemporally restricted progenitor waves with divergent fates, at which point cells adopted endothelial, hematopoietic and fibroblastic fates, respectively. During gastrulation (E6.5-E8.5), an initial wave of CD34 progenitors predominantly orchestrates vasculogenesis via a Kdr-dependent mechanism. Subsequently, from E9.5 to E14.5, cell cycle activation serves as a molecular switch, facilitating the endothelial-to-hematopoietic transition (EHT) of CD34 progenitors. Unexpectedly, we identify a wave of CD34 progenitors in late embryogenesis that gives rise to fibroblasts, distinct from earlier endothelial or hematopoietic lineages. Furthermore, because umbilical cord blood is a valuable source of different circulating stem/progenitor cells, we distinguish circulating endothelial progenitors from fibroblast progenitors in human cord blood by unique molecular signatures, with GFPT2 specifically marking the fibroblast progenitors. Collectively, our study provides a high-resolution spatiotemporal atlas of CD34 cells during embryogenesis, redefining the temporal shifts of CD34 cells in cell states and offering a precise framework for manipulating CD34 cells in regenerative medicine. - Source: PubMed
Publication date: 2026/04/03
Wang TingGong HuiYe GuoguoChen RuihanSun ShashaHuang XueyinZhang BohuanJiang LiujunZhang YueshengChen TingtingPan YuqingXu JinghongJin MinChen KaiMao WeiXu Qingbo - Intrinsic resistance to sunitinib in advanced renal cell carcinoma (RCC) remains a major barrier to improving patient survival outcomes. However, the molecular mechanisms driving this resistance remain incompletely elucidated. In this study, we first observed elevated glutamine levels in sunitinib-resistant RCC models; notably, glutamine deprivation substantially impaired the growth and proliferation of RCC cells. We further demonstrated that abnormal upregulation of GFPT2-a key enzyme in glutamine metabolism-was associated with reduced sunitinib sensitivity and enhanced drug resistance in RCC. Mechanistically, we uncovered that GFPT2 modulates cellular O-GlcNAcylation levels, which in turn enhances the stability and nuclear translocation of YAP1-ultimately contributing to reduced sunitinib sensitivity. In addition, we also identified an additional non-metabolic role of GFPT2: it directly interacts with the Kelch domain of KEAP1, thereby reducing NRF2 binding to this domain and suppressing NRF2 ubiquitination-dependent degradation. Consequently, this regulatory cascade dysregulates the transcription of downstream antioxidant genes (e.g., HMOX1 and NQO1), ultimately driving NRF2-dependent sunitinib resistance in RCC. Critically, this KEAP1-NRF2 axis-mediated mechanism operates independently of GFPT2's metabolic role in regulating O-GlcNAcylation. Collectively, our findings demonstrate that GFPT2 modulates sunitinib sensitivity and drives drug resistance in RCC via dual mechanisms: a metabolic pathway (O-GlcNAcylation-YAP1) and a non-metabolic pathway (KEAP1-NRF2). Targeting the non-metabolic functions of GFPT2 thus holds promise for enhancing sunitinib sensitivity in RCC while potentially mitigating treatment-related side effects. - Source: PubMed
Publication date: 2026/02/04
Wang SongboXing JiajunWang XiaoyiWang ZengjunShao PengfeiMiao Chenkui