Ask about this productRelated genes to: PFKFB3 antibody
- Gene:
- PFKFB3 NIH gene
- Name:
- 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 10p15.1
- Locus Type:
- gene with protein product
- Date approved:
- 1997-01-29
- Date modifiied:
- 2015-09-04
Related products to: PFKFB3 antibody
Related articles to: PFKFB3 antibody
- Metformin is a first-line therapy for type 2 diabetes, yet individual response varies significantly, with over 30 % of patients failing to achieve optimal glycemic control. The specific regulatory mechanisms of this phenomenon remain poorly understood and genetic variants involved are mainly undiscovered. There are multiple lines of evidence that the leading role in determining the variance in phenotypic outcome belongs to regulatory SNPs (rSNPs) as they directly modify gene expression. Therefore, the genome-wide search for such functional variants and deciphering associated phenotypes stands as a fundamental challenge. Previously, based on the results of bioinformatics analysis of allele-specific expression and binding landscape in human peripheral blood mononuclear cells, we have established an original panel of 14 796 rSNPs within promotors of 5132 genes. Aiming to pinpoint functional variants most likely linked to metformin hepatic response and impacts on liver gluconeogenesis, we analyzed the relevant open-access data as well as rSNPs from our panel and the corresponding genes. 1196 genes reported to be regulated by metformin in human hepatocytes and 115 genes involved in gluconeogenesis and/or its regulation via Gene Ontology annotations were intersected. Free R software and STRING v.11 tools were used for functional annotation. A number of genes harboring rSNPs within promotor regions were found to be particularly implicated in the mechanisms of metformin's action. Functional enrichment analyses revealed enrichment in critical pathways including FoxO, TNF-α and TGF-β signaling, also implicated in diabetes complications. Among these, six genes (ARPP19, ATF4, NR3C1, PFKFB3, TCF7L2, and WDR5) were strongly associated with regulation of gluconeogenesis, and may be modulated by metformin in the liver. We conclude that metformin therapy response may be influenced by the newly identified functional SNPs including rSNPs within the promotors of genes for gluconeogenic enzymes and transcription regulators. - Source: PubMed
Korbolina E EDamarov I SMerkulova T I - Programmed cell death 4 (Pdcd4) is a well-established tumor suppressor and inhibitor of protein translation. Although Pdcd4-mediated translational repression contributes to tumor suppression, emerging evidence suggests that Pdcd4 also exerts translation-independent functions. In this study, we found that Pdcd4 suppresses tumorigenesis through direct interaction with the rapamycin-insensitive companion of mTOR (Rictor), a core component of the mTORC2 complex. Using deletion mapping and site-directed mutagenesis, we defined the Rictor-binding domain of Pdcd4 and identified three critical residues, R105, K108, and R110, for this interaction. Co-immunoprecipitation and in vitro kinase assays demonstrated that Pdcd4 binding to Rictor disrupted mTORC2 complex assembly and inhibited its kinase activity. Reverse phase protein array analysis revealed that 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key regulator of glycolysis, was markedly upregulated in Pdcd4-knockdown cells. Restoration of wild-type Pdcd4, but not a Rictor-binding-deficient mutant, reduced PFKFB3 protein abundance by promoting ubiquitin-proteasome-mediated degradation. Functionally, Pdcd4-Rictor interaction suppressed glycolytic activity and inhibited tumor cell proliferation in cultured cells and xenograft models. Consistent with these findings, non-small cell lung cancer (NSCLC) tissues exhibited significantly elevated protein levels of Rictor and PFKFB3 compared with adjacent normal tissues, with a positive correlation between their expression. Collectively, these results demonstrate that the translation-independent mechanism by which Pdcd4 disrupts mTORC2 signaling and downregulates PFKFB3 plays a critical role in suppressing NSCLC growth and glycolysis. - Source: PubMed
Publication date: 2026/04/22
Yang Hsin-ShengWang QingXin YumengZokaei ElhamZeng LiangPiecoro Dava WestChen MinZhang YanquanYang KatieWang ChiLiu Xiaoqi - Myocardial infarction (MI), a leading cause of morbidity and mortality, may be treated by enhancing glycolysis in myocardial microvascular endothelial cells to promote angiogenesis. Salvia miltiorrhiza provides cardioprotection by modulating energy metabolism and angiogenesis. While our previous research identified an optimal proportion (OP) of its active components for myocardial protection, it remains unclear whether this mechanism involves the regulation of endothelial glycolysis to promote angiogenesis. - Source: PubMed
Publication date: 2026/04/28
Li WeihongTao XingruLiu KediDai QiLiu ChengzhaoYao HongWang HefeiDing ZihengChen ShaWang WenyaWei PeifengXi MiaomiaoZhang Shengyong - Pyrimidine metabolism plays a crucial role in DNA synthesis and cell proliferation and is associated with the development of various cancers. However, their prognostic value in triple-negative breast cancer remains to be further investigated. This study aimed to identify the prognostic genes related to pyrimidine metabolism in triple-negative breast cancer (TNBC). - Source: PubMed
Publication date: 2026/04/30
Gong XueDu YuboZhang HuanyuMa KeruYang DongxuChen TianyuDai SunbinLi Dalin - Resveratrol (Res), a natural polyphenolic compound, exhibits multiple antitumor activities against acute myeloid leukemia (AML), though its mechanisms remain incompletely understood. In this study, CCK-8 assay, CFSE flow cytometry, Transwell assays, and flow cytometry assessed proliferation, invasion, migration, and programmed cell death in MV4-11 and MOLM-13 leukemic cell lines. Western blotting examined cell death regulatory factors (Cleaved-caspase 3/caspase 3, Bax, Bcl-2), aerobic glycolysis proteins (GLUT1, HK2, LDHA, PKM2), cuproptosis-related proteins (FDX1, DLAT, Lip-DLAT, DLST, Lip-DLST, HSP70, SDHB), and PI3K/AKT pathway proteins (p-PI3K/PI3K, p-AKT/AKT). Intracellular Cu⁺ levels were measured colorimetrically, while glucose uptake, lactate, and ATP levels were quantified to evaluate cellular metabolism. Mechanistic investigations utilized PFKFB3 overexpression, PI3K activator (740 Y-P), and inhibitor (LY294002) intervention experiments. The antitumor efficacy of Res was validated in an AML xenograft mouse model. Res significantly inhibited AML cell proliferation, invasion, and migration while promoting apoptosis. It markedly downregulated FDX1, Lip-DLAT, Lip-DLST, and SDHB while upregulating HSP70 and intracellular Cu⁺, inducing cuproptosis-an effect reversible by the cuproptosis inhibitor TTM. Res reduced glucose uptake, lactate production, ATP generation, and downregulated GLUT1, HK2, LDHA, and PKM2, thereby suppressing aerobic glycolysis-a process reversed by PFKFB3 overexpression. Furthermore, Res inhibited PI3K and AKT phosphorylation; the PI3K activator 740 Y-P counteracted Res-mediated effects while the PI3K inhibitor LY294002 enhanced them. In vivo experiments confirmed that Res treatment markedly diminished tumor size and mass, lowered Ki-67 proliferation marker, enhanced programmed cell death, suppressed PI3K/AKT signaling, decreased glycolytic enzyme levels, and elevated copper-dependent cell death mediators. Res exerts anti-AML effects by inhibiting the PI3K/AKT pathway while coordinately regulating aerobic glycolysis and cuproptosis in AML cells. - Source: PubMed
Publication date: 2026/04/30
Lian ChengLiu YanhuiLei Pingchong