Ask about this productRelated genes to: SREBF2 Blocking Peptide
- Gene:
- SREBF2 NIH gene
- Name:
- sterol regulatory element binding transcription factor 2
- Previous symbol:
- -
- Synonyms:
- SREBP2, bHLHd2
- Chromosome:
- 22q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1994-11-23
- Date modifiied:
- 2014-11-19
Related products to: SREBF2 Blocking Peptide
Related articles to: SREBF2 Blocking Peptide
- Enhanced cholesterol synthesis and lipid droplet accumulation are hallmarks of aggressive prostate cancer, yet how tumour cells sense metabolic inputs to dynamically regulate cholesterol homeostasis remains poorly defined. Here we uncover a metabolic signalling mechanism in which prostate cancer cells remodel propionyl-CoA metabolism to support stress adaptation during disease progression. We show that the catabolism of branched-chain amino acid, specifically isoleucine and valine, is the primary source of intracellular propionyl-CoA in prostate cancer cells. Beyond its metabolic role, propionyl-CoA functions as a signalling molecule that stabilizes nuclear sterol regulatory element-binding protein 2 (SREBP2) through site-specific lysine propionylation, thereby enhancing its transcriptional activity. This activation promotes cholesterol biosynthesis, fuels de novo androgen production, and sustains androgen receptor signalling under metabolic and therapeutic stress, including androgen deprivation. Together, our findings establish propionyl-CoA as a key metabolic signal linking amino acid catabolism to cholesterol-driven oncogenic programmes and highlight targeting isoleucine and valine metabolism as a potential strategy to disrupt lipid reprogramming in prostate cancer. - Source: PubMed
Publication date: 2026/08/20
Li ZhongchiLiu ShuchenJin WenbingXiao LeyiKester OliviaBullen NayahChen XuanrongChan Un InOwiredu JudeLi ZhucuiKhan RabiaEndress JenniferShafer MoniquettaLow VivienKoundouros NikolaosCho SungyunBarbieri ChristopherGuo Chun-JunBlenis John - Corticostriatal synaptic dysfunction is an early hallmark of Huntington's disease (HD), yet the mechanisms underlying synapse loss and its reversibility remain poorly understood. Brain cholesterol is essential for neuronal and synaptic function, and dysregulated cholesterol metabolism has emerged as a key feature of HD, with reduced cholesterol biosynthesis reported in rodent models and cholesterol replenishment shown to be beneficial. Consistent with these findings, GWAS identified HD modifier loci outside canonical DNA repair pathways, including MED15, which among its functions supports SREBP2-mediated transcription of cholesterol biosynthesis genes, and a chr22 locus encompassing SREBF2, the master regulator of cholesterol biosynthesis. These findings suggest that pathways regulating cholesterol homeostasis may contribute to modifying the course of HD. Here, we show that increasing cholesterol availability prevents synapse loss and restores corticostriatal connectivity in HD models. Cholesterol supplementation restores excitatory synapse density in vivo and in vitro. In primary HD neurons, cholesterol stabilizes dendritic spines and promotes the enrichment of GluA1-containing AMPA receptors in mature mushroom spines during chemically induced long-term potentiation, consistent with improved synaptic plasticity. Using microfluidic devices to spatially resolve the corticostriatal circuitry, we identified a compartment-specific mechanism whereby cholesterol delivery to cortical neurons is necessary and sufficient to restore corticostriatal connectivity, whereas cholesterol administration to the striatal compartment selectively restores intrastriatal inhibitory synapses. Mechanistically, NMDA receptor and BDNF/TrkB signalling mediate the cholesterol-dependent restoration of synaptic connectivity, establishing cholesterol as a critical regulator of corticostriatal synaptic integrity in HD and supporting targeting cholesterol homeostasis as a therapeutic strategy to restore synaptic function. - Source: PubMed
Publication date: 2026/08/12
Lenci AllegraVilla MichelaScolz AndreaBirolini GiuliaConforti PaolaPepe GiuseppeCastagno Antonio NicolasCassarino ChristianColombo LauraFavagrossa MonicaPolimeno AntoninoOttoboni LindaCorti StefaniaPardo Alba DiSalmona MarioMaglione VittorioZuccato ChiaraCattaneo Elena - Tumour cells commonly exhibit aerobic glycolysis and produce lactate despite oxygen availability. Lactate dehydrogenase (LDH) catalyses pyruvate-lactate interconversion and regulates intracellular lactate levels. Endothelial cells also depend on glycolysis for ATP production, which prompted us to investigate LDH in canine hemangiosarcoma (HSA), a malignant endothelial tumour. We inhibited LDH with (R)-GNE-140 or sodium oxamate in two canine HSA cell lines (HU-HSA-2 and HU-HSA-3) and generated HU-HSA-3 clones with knockout of LDHA or LDHB to evaluate the effects of LDH perturbation. (R)-GNE-140 and sodium oxamate suppressed proliferation and reduced global histone lactylation levels in both cell lines. mRNA-sequencing (mRNA-seq) of (R)-GNE-140-treated HU-HSA-2 cells identified cholesterol/lipid metabolism-related gene sets among the top negatively enriched pathways. Representative cholesterol/lipid metabolism genes such as SREBF2, SQLE and LDLR responded differently depending on cell lines and inhibitors. (R)-GNE-140 decreased these genes in HU-HSA-2 but not HU-HSA-3, whereas sodium oxamate decreased them in HU-HSA-3 with limited effects in HU-HSA-2. In HU-HSA-3, LDHA and LDHB knockout clones decreased SREBP2 expression and reduced the number of lipid droplets. Fluvastatin, a cholesterol metabolism inhibitor, inhibited HSA cell growth in vitro but did not significantly suppress tumour growth in two HSA patient-derived xenograft (PDX) models. In contrast, combined fluvastatin and dipyridamole treatment inhibited proliferation in vitro and tumour growth in PDX models. Collectively, these results suggest a context-dependent association between LDH and cholesterol/lipid metabolism in canine HSA cell lines and provide a rationale for further evaluation of combined cholesterol pathway inhibition. - Source: PubMed
Publication date: 2026/08/10
Suzuki TamamiTanaka SuzuneKishimoto KeikaGoto TakumaYamazaki JumpeiKimura TakashiAoshima Keisuke - Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited diagnostic tools and therapeutic options. Dysregulated mitophagy in astrocytes plays a pivotal role in AD pathogenesis. This study aims to identify a mitophagy and astrocyte (MA)-associated molecular signature for AD diagnosis and therapeutic targeting. - Source: PubMed
Publication date: 2026/07/24
Liu JiachengChen Wei - Cancer recurrence and distant metastasis are major causes of cancer-related death, yet existing biomarkers and single-omics models have limited accuracy and interpretability across tumor types. - Source: PubMed
Publication date: 2026/07/15
Li JunxianXing YuchenGao XiminLiu Renhe