SREBF2 antibody - middle region (P100696_P050)
- Known as:
- SREBF2 (anti-) - middle region (P100696_P050)
- Catalog number:
- p100696_p050
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Aviva Systems Biology
- Gene target:
- SREBF2 antibody - middle region (P100696_P050)
Related genes to: SREBF2 antibody - middle region (P100696_P050)
- 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 antibody - middle region (P100696_P050)
Related articles to: SREBF2 antibody - middle region (P100696_P050)
- Post-stroke neurological decline is associated with persistent vascular and metabolic dysfunction, including long-term alterations in lipid homeostasis. We performed targeted lipidomic analyses in the hippocampus and plasma from rats subjected to transient middle cerebral artery occlusion at 6 h, 24 h, 7 days, 15 days, 1 month, and 4 months after stroke. Lipid profiles were integrated with behavioral, histological, immunofluorescence, western blot, flow cytometric, and bioinformatic analyses. At 4 months, an increased plasma lysophosphatidylcholine/phosphatidylcholine ratio was associated with late neurological deterioration and cognitive impairment. This change coincided with hippocampal lipid remodeling, region-specific astrogliosis, changes in PLA2, LPCAT1, MBOAT1, and SREBF2, and altered circulating BODIPY lipophilic particles associated with apolipoproteins. These findings support coordinated central and peripheral lipid remodeling during chronic post-ischemic progression with potential relevance for peripheral biomarker development. - Source: PubMed
Publication date: 2026/09/05
Salomón-Cruz Iván DanielGutiérrez-Vargas JohannaCardona-Gómez Gloria Patricia - Proteasome inhibitors, particularly bortezomib (BTZ) which induces oxidative stress, remain the cornerstone of multiple myeloma (MM) therapy. However, resistance driven by metabolic reprogramming and redox adaptation limits their long-term efficacy. Here, we identify a cholesterol biosynthesis-dependent antioxidant mechanism that shields MM cells from BTZ-induced generation of reactive oxygen species (ROS). High cholesterol biosynthesis activity characterizes BTZ-nonresponsive plasma cells and correlates with poor prognosis. Genetic silencing of SREBF2, the master transcriptional regulator of cholesterol metabolism, sensitized MM cells to BTZ both in vitro and in vivo. Pharmacological inhibition of HMG-CoA reductase, the rate-limiting enzyme of cholesterol biosynthesis, with the clinically approved atorvastatin likewise enhanced the anti-myeloma activity of BTZ in vitro and in vivo. Mechanistically, the lipid raft protein FLOT1 promoted FOXO3 nuclear translocation and SREBF2 activation, thereby driving increased cholesterol biosynthesis and accumulation of the intermediate metabolite 7-dehydrocholesterol (7-DHC), a critical antioxidant that mitigated BTZ-induced cytotoxicity. Decreasing 7-DHC production by disrupting SREBF2 activation or treating with atorvastatin impaired the cellular ROS detoxification capacity and enhanced BTZ-induced cytotoxicity. Collectively, our findings identify that MM cells resist therapy-induced ROS by accumulating 7-DHC through activation of cholesterol biosynthesis, and provide preclinical evidence for repurposing statins to augment the efficacy of BTZ therapy. - Source: PubMed
Publication date: 2026/09/21
Li ChunfanWang FuqiangPeng HongweiChen MengPu YafangLin XiangWang ShuaiLi FeiGu Zhimin - Mosunetuzumab is highly effective against many B-cell lymphomas, but longitudinal immune changes induced by intermittently dosed CD20×CD3 bispecific antibodies remain incompletely characterized. We performed immune profiling of peripheral blood samples from patients receiving fixed-duration (6 months) subcutaneous mosunetuzumab for previously untreated follicular or marginal zone lymphoma on a phase 2 clinical trial (NCT04792502). Analyses included flow cytometry, cytokine profiling, and RNA-seq of isolated CD8+ T-cells with TCR repertoire inference. Early (at 3 weeks) on-treatment samples showed broad cytokine induction, CD8+ T-cell redistribution with decreased TEMRA cells and increased CD27+CD62L+ transitional effector memory-like cells, increased PD-1 and LAG-3 expression, and induction of CD8+ transcriptional programs consistent with activation, proliferation, exhaustion priming, and SREBF2-regulated cholesterol metabolism. By mid-treatment (at 3 months), activation-associated features contracted toward baseline, with no evidence of phenotypic exhaustion, though with persistent overexpression of LAG3, HAVCR2, and LAYN on RNA-seq, as well as sustained SREBF2 activation. CD8+ T-cell clonality increased at mid-treatment compared with baseline and higher clonality was associated with early clinical complete response. Mosunetuzumab also induced indirect NK-cell activation and expansion, including skewing toward CD56dimCD16bright effector state. HLA-DR upregulation on NK cells correlated with early increases in NK-activating plasma cytokines, and higher NK-cell count at mid-treatment was associated with complete response. Together, these findings define a CD8+ effector-remodeling state on mosunetuzumab therapy, characterized by clonal expansion, selective inhibitory receptor expression, sustained activation of cholesterol biosynthesis, and cytokine-linked engagement of innate immune mechanisms, providing a framework for potential strategies to support T-cell function and enhance bispecific antibody efficacy. - Source: PubMed
Publication date: 2026/09/10
Milrod Charles JChorzalska Anna DorotaBonal Dennis MMorgan JohnPardo MakaylaOllila Thomas APelcovits AriRaker ChristinaTreaba Diana OlgutaMcMahon JessicaDonnelly StephenCarmody CayleeMargolis JeannineMatasar Matthew JHuntington Scott FDubielecka Patrycja MOlszewski Adam J - Activated CD8 T cells undergo metabolic reprogramming and shift to aerobic glycolysis to fulfill their energy and biosynthetic demands. However, the downstream pathways linking glycolytic flux to potent antitumor immunity remain unclear. In this study, we used a T-cell-specific phosphoglycerate mutase 1 (Pgam1)-deficient mouse model to demonstrate that accelerated lipid synthesis induced by glycolysis is necessary for CD8 T cells to acquire antitumor activity. Pgam1 deficiency severely impaired antitumor activity and intratumoral infiltration in the MC38-OVA tumor model. Transcriptomic profiling of Pgam1-deficient CD8 T cells activated in vitro revealed that Pgam1 deficiency caused a marked reduction in the lipid biosynthetic program and altered lipid composition. We found that in Pgam1-deficient CD8 T cells, TCR stimulation dose not induce the upregulation of the Srebf1 and Srebf2 genes, which encode the master transcription factors Srebp1 and Srebp2, respectively, that regulate lipid synthesis. Pharmacological inhibition of SREBPs by fatostatin attenuated effector functions, such as TCR-induced proliferation, cytokine production, and cytotoxicity. These findings indicate that the activation of SREBP-dependent lipid synthesis pathways, which follow glycolysis, is important for the acquisition of antitumor activity by CD8 T cells. - Source: PubMed
Publication date: 2026/09/05
Hamada TaisukeKuwahara MakotoTokiwa HirokiYamamoto WaichiSuzuki JunpeiNomura ShunsukeMatsuoka YukoMatsushita TakahumiKitamura SakikoKawashima AyatoNishihara TasukuYamashita Masakatsu - Neuroinflammation often disrupts cerebral cholesterol homeostasis and leads to white matter damage and demyelination. However, the molecular mechanisms underlying these defects have remained enigmatic. In this study, we report that inflammation is associated with aberrant activation of Wnt signaling in astrocytes. While Wnt signaling increases astrocytic expression of SREBF2 protein and intracellular cholesterol level, it simultaneously inhibits the expression of APOE and reduces cholesterol efflux from astrocytes. The extracellular cholesterol supply is essential for the activation of the expression of MYRF transcription factor and myelin-associated genes in oligodendrocytes. Moreover, the defective oligodendrocyte differentiation and myelin gene expression caused by astrocytic Wnt activation in transgenic mice can partially be rescued by chemical-enhanced ApoE expression. Our findings suggest a regulatory pathway of "inflammation → Wnt signaling → cholesterol metabolism → myelin integrity" and provide important insights into the molecular mechanisms underlying inflammation-induced demyelinating diseases and future therapeutic strategies. - Source: PubMed
Publication date: 2026/09/02
Zhang JiannanZheng JiaruAi YiYang JunlinHe ChengZhao JingweiQiu MengshengZheng Kang