Anti-Mouse NFE2L1 (FLJ00380), Rabbit Polyclonal
- Known as:
- Antibody toMouse NFE2L1 (FLJ00380), Rabbit Polyclonal
- Catalog number:
- mfl0380
- Product Quantity:
- EUR
- Category:
- -
- Supplier:
- Sceti
- Gene target:
- Anti-Mouse NFE2L1 (FLJ00380) Rabbit Polyclonal
Related genes to: Anti-Mouse NFE2L1 (FLJ00380), Rabbit Polyclonal
- Gene:
- NFE2L1 NIH gene
- Name:
- nuclear factor, erythroid 2 like 1
- Previous symbol:
- TCF11
- Synonyms:
- NRF1, LCR-F1, FLJ00380
- Chromosome:
- 17q21.3
- Locus Type:
- gene with protein product
- Date approved:
- 1994-03-24
- Date modifiied:
- 2015-11-18
Related products to: Anti-Mouse NFE2L1 (FLJ00380), Rabbit Polyclonal
Related articles to: Anti-Mouse NFE2L1 (FLJ00380), Rabbit Polyclonal
- Cholesterol overload contributes to metabolic dysfunction-associated steatohepatitis (MASH) progression. One major pathway that limits hepatic cholesterol accumulation is export via VLDL secretion. While sterol regulatory element-binding protein (SREBP) activity is suppressed by insulin-induced gene 1 (INSIG1) under high sterol conditions, VLDL secretion nonetheless persists to prevent lipotoxicity and liver injury, presenting an unresolved paradox in cholesterol sensing and lipoprotein export. Here, we identified a cholesterol-responsive interaction between nuclear factor erythroid 2 related factor-1 (NFE2L1) and INSIG1 that preserved cholesterol homeostasis by sustaining VLDL secretion. Liver-specific NFE2L1 deletion elevated INSIG1 abundance, suppressed SREBP1 activation, and impaired VLDL secretion, leading to hepatic cholesterol accumulation and liver injury. Mechanistically, NFE2L1 bound to INSIG1 via its N-terminal homology box 2 (NHB2) domain; free cholesterol strengthened this interaction to promote INSIG1 degradation, thereby enabling SREBP1 activation and VLDL export. In NFE2L1-deficient mice, WT NFE2L1, but not a mutant NFE2L1 form unable to interact with INSIG1 (NHB2-deleted mutant, ΔNHB2), restored SREBP1 activity and VLDL secretion. Lipidomics analysis revealed that NFE2L1 deficiency reduced serum triglyceride composition, which was restored exclusively by WT NFE2L1. In a murine MASH model, NFE2L1 overexpression activated SREBP1/2, lowered hepatic cholesterol, and attenuated liver injury, inflammation, and fibrosis, without elevating atherogenic lipoproteins owing to compensatory LDL receptor upregulation. Together, these findings explain how VLDL secretion capacity was maintained under cholesterol excess and identify the NFE2L1/INSIG1 axis as a sterol-responsive safeguard for hepatic lipid homeostasis and a potential therapeutic target for MASH. - Source: PubMed
Publication date: 2026/07/15
Deng ShijunFreed Jessica ELee Grace YAskin GizelCao ZheCakici ÖzgürYuan BoHui Sheng TonyInouye Karen EGraupera IsabelHotamışlıgil Gökhan S - Metabolic dysfunction-associated steatohepatitis (MASH) affects 1.5%-6.5% of the global population, yet its mechanisms remain incompletely understood. Cholesterol overload is a key driver of MASH, suggesting that targeting cholesterol sensing may offer therapeutic benefits. In this issue, Deng et al. identified nuclear factor erythroid 2-related factor 1 (NFE2L1) as a critical regulator linking cholesterol sensing to VLDL-mediated lipid export. Mechanistically, NFE2L1 interacts with insulin-induced gene 1 (INSIG1) and promotes its degradation in hepatocytes. This cholesterol-dependent NFE2L1-INSIG1 interaction sustains SREBP activation and VLDL secretion to maintain hepatic and systemic lipid homeostasis. Moreover, the study by Deng et al. indicates that hepatic NFE2L1 overexpression decreases INSIG1 abundance and ameliorates MASH progression, highlighting its therapeutic potential. - Source: PubMed
Publication date: 2026/07/15
Zang MengweiLi Yu - Multiple myeloma (MM) is a plasma-cell malignancy driven by dysregulated NF-κB signaling, promoting tumor survival, proliferation, and chemoresistance. Given observed overexpression of NF-κB components in MM cell lines, we evaluated the selective NF-κB inhibitor QNZ (EVP4593) for anti-myeloma activity. QNZ selectively reduced viability and inhibited proliferation of MM cells and , though stromal contact partly attenuated its cytotoxicity. QNZ dose-dependently suppressed MM xenografts, increased apoptosis, and reduced proliferation, while preserving MM plasma cell identity. Mechanistically, QNZ triggered mitochondrial, caspase- (cleavage of pro-caspase-9, -8 and -3) and PARP-mediated apoptosis with downregulation of Mcl-1, dismantled pro-survival NF-κB/Akt/c-Myc signaling with concomitant mTOR modulation, and induced cell-cycle perturbation accompanied by altered phospho-ATM and decreased levels of key regulators (SIRT1, Chk2/p-Chk2, Cdc2/p-Cdc2, p-4EBP1, CDK4, cyclin A2, and cyclin B1). Transcriptomic profiling demonstrated that QNZ treatment induced extensive gene expression reprogramming in MM cells, prominently upregulating stress- and metabolism-associated genes including DDIT3, PHGDH, SESN2, and NFE2L1, consistent with activation of ER stress-mediated apoptotic and amino acid metabolic pathways. Finally, QNZ displayed significant synergy with proteasome inhibitors and IMiDs, particularly second-generation carfilzomib and pomalidomide, as well as with dexamethasone and melphalan, providing a strong preclinical rationale for clinical evaluation of QNZ in MM. - Source: PubMed
Publication date: 2026/06/12
Cholujova DanaValuskova ZuzanaBurikova MonikaHucko MilanBeke GaborSedlackova EvaKlucar LubosSuroviakova KatarinaGrofova GabrielaSedlak JanJakubikova Jana - Nuclear factor erythroid 2-related factor 1 (Nrf1, encoded by NFE2L1) plays a central role in maintaining cellular homeostasis, basal redox balance, and mitochondrial quality control and its function. Recent studies have revealed that Nrf1 assumes complex, even opposing, roles in functioning both as a tumor-suppressor and otherwise, also as an unconvincing driver of Hepatocellular carcinoma (HCC) progression through certain oncogenic pathways and redox stress adaptation. - Source: PubMed
Publication date: 2026/06/29
Chen XiZhang ZhengwenCui SiqianZhang Yiguo - The mechanisms by which cancer cells survive and adapt under high levels of reactive oxygen species (ROS) remain poorly understood, especially in the context of redox homeostasis. This study reveals increased oxidative stress in esophageal squamous cell carcinoma (ESCC), with serine/arginine-rich splicing factor 6 (SRSF6) playing a crucial role in maintaining redox homeostasis. SRSF6 binds to the exonic splicing enhancer (ESE) motif in nuclear factor erythroid 2-related factor 1 (NFE2L1 Exon 4, preventing exon skipping and promoting the production of specific isoforms that promote ESCC cell proliferation. This interaction enhances cellular antioxidant capacity, thereby influencing redox balance. Moreover, reducing SRSF6 increases the levels of NFE2L1-S, the isoform produced by exon 4 skipping in the gene, which elevates ROS levels and induces apoptosis and ferroptosis. Notably, SRSF6 and NFE2L1 form a positive feedback loop: NFE2L1 serves as the transcription factor for SRSF6, while SRSF6 acts as the splicing factor for NFE2L1. Antisense oligonucleotides (ASOs) targeting SRSF6 significantly suppress ESCC cell growth. Importantly, inhibiting this feedback loop also enhances cisplatin (CDDP) sensitivity, increasing the therapeutic efficacy of CDDP. Our findings highlight the critical role of the SRSF6-NFE2L1 axis in redox homeostasis and tumor progression, positioning SRSF6 as a distinctive therapeutic target to improve treatment outcomes in ESCC. - Source: PubMed
Publication date: 2026/06/10
He XinyuXu JialuoDuan LinaMa JingGao DanXie YifeiZhao DengyunLiu JialinZhao JiminLiu FangfangLee Mee-HyunKim Myoung OkDong ZigangJiang YananLiu Kangdong