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Showing SREBF2 — SREBP2 is a alias.

SREBF2

Sterol regulatory element-binding protein 2 · UniProt Q12772

Length
1141 aa
Mass
123.7 kDa
Annotated
2026-06-10
100 papers in source corpus 50 papers cited in narrative 50 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SREBF2 encodes SREBP2, a membrane-bound basic helix-loop-helix-leucine zipper transcription factor that serves as a master regulator of cholesterol homeostasis: under sterol-poor conditions a sterol-regulated protease cleaves the membrane-attached precursor to release its N-terminal bHLH-Zip domain, which enters the nucleus to transactivate sterol-responsive genes (PMID:7759101). SREBP2 is subject to negative feedback through a perfect sterol regulatory element (SRE-1) in its own promoter, providing autoregulatory control by sterol levels (PMID:9070916, PMID:31356817). Its direct transcriptional target repertoire spans cholesterol uptake and synthesis (LDLR, HMGCR, PCSK9, NPC1L1, SQLE, the lipid transporters ABCA7 and STARD4) (PMID:16788211, PMID:20460578, PMID:35642354, PMID:31356817, PMID:33687065), and the locus is bifunctional, co-expressing intronic miR-33a that post-transcriptionally suppresses ABCA1, ABCG1, and fatty-acid β-oxidation enzymes (CPT1A, HADHB, CROT), coupling SREBP2-driven anabolism to repression of cholesterol efflux and lipid catabolism (PMID:20566875, PMID:20732877). SREBP2 activation is gated at the proteolytic-processing step by the SCAP machinery, which integrates numerous inputs: Akt is required for ER-to-Golgi transport of SREBP2 (PMID:22005015, PMID:29122977), RNF5-mediated ubiquitination of SCAP promotes the conformational change needed for activation (PMID:32054686), AMPK signaling is inhibitory (PMID:27211556), ER Ca2+ is required for processing (PMID:35140212), and the mature nuclear protein is stabilized against ubiquitin-dependent degradation by USP28 (PMID:37202505). Nuclear SREBP2 acts through phase-separated condensates formed by its N-terminal intrinsically disordered region, which co-localize with coactivators at superenhancers to drive lipogenic transcription; abolishing condensate formation lowers transcriptional activity and circulating cholesterol (PMID:40394324). SREBP2 is essential for embryonic development and tissue homeostasis—its loss causes embryonic lethality and limb defects, and a hypomorphic point mutation produces nuclear cataracts and skin defects with reduced tissue cholesterol (PMID:26685326, PMID:21858719)—and it has dedicated roles in oligodendrocyte myelinogenesis as a Qki co-activated regulator of brain cholesterol synthesis (PMID:33942715). Beyond canonical lipid metabolism, SREBP2 directly transactivates non-lipogenic targets to drive disease programs, including mesenchymal genes in endothelial-to-mesenchymal transition (PMID:34806652), NLRC4 in keratinocyte inflammation (PMID:35120997), and transferrin to suppress ferroptosis (PMID:33203734), and is co-opted across cancers and pathogens through caspase-3-mediated cleavage and stabilization (PMID:35767704, PMID:36097162, PMID:38728412).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1995 High

    Established the founding mechanistic model: SREBP2 is a membrane-tethered bHLH-Zip transcription factor activated by sterol-regulated proteolysis that liberates a nuclear transcriptional domain.

    Evidence Gene cloning, FISH mapping, and structural characterization defining domain architecture and proteolytic activation

    PMID:7759101

    Open questions at the time
    • Identity of the regulated protease and the full upstream transport machinery not resolved here
    • Genome-wide target spectrum unknown at this stage
  2. 1997 High

    Defined the autoregulatory logic of the pathway by locating a functional SRE-1 in the SREBF2 promoter, showing the transcription factor regulates its own gene by sterol levels.

    Evidence Genomic cloning, sequencing, and promoter analysis of the 19-exon SREBF2 locus

    PMID:9070916

    Open questions at the time
    • Did not establish quantitative feedback dynamics in vivo
  3. 2004 High

    Identified a direct protein-protein brake on SREBP2 output: ATF6(N) binds SREBP2(N) via its leucine zipper and recruits HDAC1 at SRE promoters to suppress lipogenesis, linking the unfolded protein response to cholesterol synthesis.

    Evidence Reciprocal GST pull-down/co-IP, deletion mapping, and ChIP in liver cells under glucose deprivation

    PMID:14765107

    Open questions at the time
    • Stoichiometry and genomic breadth of ATF6-SREBP2 co-occupancy not defined
    • In vivo physiological contribution not quantified
  4. 2006 Medium

    Expanded the direct target set to lipid transporters, showing SREBP2 binds SREs in ABCA7 (opposite to LXR) and that ABCG1/ABCG4-controlled sterol distribution feeds back on SREBP2 processing.

    Evidence Promoter/SRE analysis with forced expression and siRNA (ABCA7); Abcg4 knockout plus overexpression with SREBP2 processing readout (CNS cells)

    PMID:16788211 PMID:17916878

    Open questions at the time
    • Direct ChIP for SREBP2 at ABCA7 not explicitly shown
    • Tissue specificity of these regulatory relationships incompletely mapped
  5. 2010 High

    Revealed the SREBF2 locus as bifunctional: intronic miR-33a is co-expressed with SREBP2 and suppresses ABCA1/ABCG1 and β-oxidation enzymes, coordinating anabolic transcription with repression of efflux and catabolism.

    Evidence 3' UTR/luciferase target validation, hepatic gain/loss of function in vivo, cholesterol efflux and HDL measurement; replicated across labs

    PMID:20566875 PMID:20732877

    Open questions at the time
    • Relative contribution of miR-33 vs SREBP2 protein to net lipid phenotype not partitioned
  6. 2010 Medium

    Extended direct transcriptional targeting to the intestinal sterol absorption transporter NPC1L1, confirmed by in vivo promoter occupancy.

    Evidence Promoter-reporter, ChIP in HuH7 cells, and dose-dependent overexpression

    PMID:20460578

    Open questions at the time
    • Physiological impact on dietary cholesterol absorption not tested genetically
  7. 2011 Medium

    Placed Akt kinase as a direct upstream activator acting on the processing/transport step, linking growth-factor signaling to acute SREBP2 activation.

    Evidence IGF-1 stimulation, Akt inhibitors, siRNA, and rapalog-inducible Akt heterodimerization with SREBP2 activation assay

    PMID:22005015

    Open questions at the time
    • Direct phosphorylation substrate within the transport machinery not pinpointed in this study
  8. 2014 Medium

    Established physiological in vivo control nodes: hepatic insulin receptor signaling is required for feeding- and statin-induced SREBP2 (likely via cholesterol distribution), and intestinal SREBP2 activation alone is sufficient to cause hypercholesterolemia.

    Evidence Liver-specific insulin receptor knockout with ezetimibe rescue; villin-promoter active-SREBP2 transgenic mice with lipid phenotyping

    PMID:24465397 PMID:24516236

    Open questions at the time
    • Mechanistic link between insulin and intracellular cholesterol redistribution remains indirect
  9. 2015 High

    Demonstrated SREBP2 is essential for embryonic development and that its activity can be uncoupled from its transcription, since FXR induces Srebp2 mRNA and miR-33 yet blocks mature protein production by inducing INSIG-2A.

    Evidence SREBP2 knockout/hypomorphic mice with embryo analysis; FXR agonists, ChIP-seq FXR response element, and Scap-/- validation

    PMID:25593129 PMID:26685326

    Open questions at the time
    • Developmental targets of SREBP2 driving limb/morphogenic defects not identified
    • Physiological settings where the transcription/processing uncoupling dominates not delineated
  10. 2015 High

    Genetically confirmed SREBP2 as essential for tissue homeostasis: a hypomorphic regulatory-domain missense mutation causes cataracts, skin defects, and reduced tissue cholesterol, with causality proven by complementation testing.

    Evidence lop13 spontaneous R1038C mutant, linkage, complementation with gene-trap allele, GC cholesterol measurement

    PMID:21858719

    Open questions at the time
    • Molecular consequence of the R1038C regulatory-domain mutation on processing not mechanistically dissected
  11. 2020 High

    Resolved how SCAP conformational activation is post-translationally licensed and how mature SREBP2 abundance is controlled, identifying RNF5-mediated SCAP ubiquitination and USP28 deubiquitination of nuclear SREBP2 as opposing controls.

    Evidence RNF5 ubiquitination assays and K305R SCAP rescue; USP28 co-IP, deubiquitination assays, and statin-sensitivity rescue with GGPP

    PMID:32054686 PMID:37202505

    Open questions at the time
    • Counteracting E3 ligase for mature SREBP2 not defined
    • Signals that toggle RNF5/USP28 activity not established
  12. 2020 Medium

    Uncovered non-canonical SREBP2 functions beyond lipid synthesis, including direct transactivation of transferrin to suppress ferroptosis in metastatic melanoma and caspase-3-mediated cleavage driving cancer stemness and drug resistance.

    Evidence Single-cell CTC analysis with TF knockdown and ferroptosis rescue; caspase-3 cleavage assay, SREBP2 loss-of-function, and xenografts in HCC

    PMID:33203734 PMID:35767704

    Open questions at the time
    • Generality of caspase-3 cleavage as a physiological activation route unclear
    • Whether TF is a canonical SRE-driven target not detailed
  13. 2021 Medium

    Defined a tissue-specific developmental role through co-activator partnership, with Qki-5 acting as a transcriptional co-activator of Srebp2 to drive oligodendrocyte cholesterol synthesis and myelinogenesis.

    Evidence Qki conditional knockout in neural stem cells/OPCs with RNA-seq, cholesterol measurement, and myelination assays

    PMID:33942715

    Open questions at the time
    • Direct biochemical Qki-SREBP2 interaction interface not mapped
  14. 2021 Medium

    Showed SREBP2 directly transactivates non-lipogenic disease-driver genes, binding promoters of mesenchymal genes (EndMT) and YAP and NLRC4 in inflammation.

    Evidence ChIP for promoter binding, EC-specific transgenic mice, and siRNA rescue across fibrosis, hyperuricemia, and psoriasis models

    PMID:33977576 PMID:34806652 PMID:35120997

    Open questions at the time
    • Whether these targets require canonical SREs or alternative motifs not resolved
    • Sterol-dependence of these programs unclear
  15. 2022 Medium

    Identified ER Ca2+ as a required input to processing and mapped additional protein stabilizers (XBP1-u, KIF11) and a direct mitochondrial-cholesterol target (STARD4), explaining drug-resistance phenotypes in cancer.

    Evidence Caffeine/ER-Ca2+ manipulation with processing and PCSK9/LDLR readout; co-localization/ubiquitination assays; ChIP at STARD4 promoter with rescue

    PMID:35140212 PMID:35619540 PMID:35642354 PMID:35933495

    Open questions at the time
    • KIF11-SREBP2 interaction rests on single co-IP without reciprocal validation
    • Mechanism by which ER Ca2+ gates SCAP-mediated processing not detailed
  16. 2023 Medium

    Continued mapping of upstream SCAP-level regulators, adding PKCλ/ι phosphorylation-driven SCAP degradation and SNX10-controlled ERLIN2-SCAP dissociation as brakes whose loss drives intestinal tumor/stem-cell programs.

    Evidence Conditional knockouts in intestinal epithelium with SCAP phosphorylation/degradation and SREBP2 processing assays

    PMID:37647408 PMID:38092754

    Open questions at the time
    • Interplay among RNF5, PKCλ/ι, SNX10, and ERLIN2 at SCAP not integrated
  17. 2024 Medium

    Linked SREBP2 to tumor immune evasion and lipid-peroxidation signaling, showing tumor lactate activates SREBP2 to generate immunosuppressive regulatory dendritic cells and that ALOX15B-ERK1/2 raises nuclear SREBP2 in macrophages.

    Evidence DC-specific SREBP2 silencing with T-cell and tumor readouts; ALOX15B siRNA in primary human macrophages with sterol-intermediate mass spectrometry

    PMID:38581859 PMID:38728412

    Open questions at the time
    • Whether SREBP2's immunosuppressive role is purely mevalonate-dependent not fully separated
  18. 2025 High

    Provided a biophysical mechanism for nuclear SREBP2 transactivation, showing its N-terminal IDR drives phase-separated condensates at superenhancers required for full lipogenic transcription in vivo.

    Evidence Phase-separation assays, IDR Phe→Ala mutagenesis with FUS-IDR rescue, ChIP-seq, and knock-in mouse with cholesterol phenotyping

    PMID:40394324

    Open questions at the time
    • Coactivators recruited into condensates not exhaustively identified
    • How sterol signaling tunes condensate dynamics unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many upstream SCAP-level regulators, nuclear stabilizers, and condensate dynamics are integrated into a unified quantitative model of context-specific SREBP2 output, and which mechanisms govern its expanding non-lipogenic target programs, remain open.
  • No unified model linking processing-level and stability-level control
  • Sterol-dependence of non-canonical targets unresolved
  • Structural basis of target selection between lipogenic and non-lipogenic promoters unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0003677 DNA binding 6
Localization
GO:0005783 endoplasmic reticulum 4 GO:0005634 nucleus 3 GO:0005794 Golgi apparatus 2
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-1430728 Metabolism 6 R-HSA-8953897 Cellular responses to stimuli 3
Partners
AKT1ATF6KIF11QKIRNF5SCAPUSP28XBP1

Evidence

Reading pass · 50 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 SREBP2 (SREBF2) encodes a transcription factor with an NH2-terminal basic helix-loop-helix-leucine zipper (bHLH-Zip) domain followed by a membrane attachment domain; proteolytic cleavage by a sterol-regulated protease releases the bHLH-Zip domain from the membrane, allowing nuclear entry and transcriptional activation of sterol-regulated genes (LDL receptor, HMG-CoA synthase). SREBF2 maps to chromosome 22q13. Gene cloning, somatic cell hybrid analysis, fluorescence in situ hybridization, structural characterization Genomics High 7759101
1997 The SREBF2 gene spans 72 kb, comprises 19 exons and 18 introns, and contains a perfect 10-bp sterol regulatory element (SRE-1) in its own promoter region, indicating autoregulatory control of SREBP2 transcription by sterol levels. Gene cloning, sequencing, promoter analysis, transcription start site mapping Genomics High 9070916
2004 ATF6(N) (the cleaved nuclear form of ATF6) physically binds SREBP2(N) through its leucine-zipper domain, and the ATF6-SREBP2 complex on SRE-bound promoters recruits HDAC1, thereby suppressing SREBP2 transcriptional activity and reducing lipogenesis in liver cells. Glucose deprivation activates ATF6 and suppresses SREBP2-regulated transcription via this mechanism; blocking ATF6 cleavage by BiP/GRP78 reverses this inhibition. GST pull-down, co-immunoprecipitation, deletion mutagenesis, chromatin immunoprecipitation, overexpression in liver cells The EMBO journal High 14765107
2006 Overexpression of either ABCG1 or ABCG4 in CNS cells increases the proteolytic processing of SREBP2 to its transcriptionally active form, inducing SREBP2 target genes and cholesterol synthesis; conversely, Abcg1 or Abcg4 knockout represses SREBP2 target gene expression in brain. Both ABCG1 and ABCG4 reside in RhoB-positive endocytic vesicle membranes and regulate intracellular sterol/cholesterol distribution upstream of SREBP2 activation. Abcg4 knockout mice, primary cell culture (astrocytes, microglia, neurons, macrophages), overexpression, cellular localization studies, gene expression analysis Journal of lipid research Medium 17916878
2006 SREBP2 directly binds to a sterol regulatory element (SRE) in the ABCA7 promoter and activates ABCA7 transcription in response to low cellular cholesterol, opposite to the LXR-driven regulation of ABCA1. Chromatin immunoprecipitation and promoter analysis identified the 9-bp SRE at positions −212 bp (mouse) and −179 bp (human) upstream of the ABCA7 transcription start site. Promoter analysis, SREBP2 forced expression/knockdown with siRNA, ChIP-implied promoter binding (promoter characterization with identified SRE) Journal of lipid research Medium 16788211
2010 miR-33a is encoded within intron 16 of the SREBF2 gene and is co-expressed with SREBP2 mRNA. miR-33 targets the 3′ UTR of ABCA1 and ABCG1, suppressing their translation and reducing LXR-dependent cholesterol efflux to ApoAI and serum; hepatic overexpression of miR-33 decreases ABCA1 protein and plasma HDL, while miR-33 silencing increases them. Co-expression analysis, 3′ UTR targeting assays, hepatic overexpression and silencing of miR-33 in vivo, cholesterol efflux assays, plasma HDL measurement Proceedings of the National Academy of Sciences of the United States of America High 20566875 20732877
2010 miR-33, encoded within SREBF2 intron, also inhibits translation of CPT1A, HADHB, and CROT (proteins involved in fatty acid β-oxidation), thereby reducing fatty acid degradation in addition to suppressing ABCA1-mediated cholesterol export. Luciferase reporter assays, miRNA overexpression, protein expression analysis, fatty acid oxidation assays The Journal of biological chemistry High 20732877
2010 SREBP2 directly regulates NPC1L1 promoter activity and mRNA expression in a dose-dependent manner; chromatin immunoprecipitation confirmed that SREBP2 binds the NPC1L1 promoter in vivo in HuH7 cells. HNF1α also independently activates NPC1L1 transcription through a distinct HNF1 binding site. Correlation analysis in human liver samples, promoter-reporter assay, ChIP assay, SREBP2 and HNF1α overexpression in HuH7 cells Journal of lipid research Medium 20460578
2011 Akt kinase activation (via IGF-1 stimulation or rapalog-induced Akt heterodimerization) acutely activates SREBP2 within 1 hour; pharmacological or siRNA-mediated Akt inhibition blunts SREBP2 activation, establishing Akt as a direct upstream activator of SREBP2 processing/activation in cholesterol metabolism. IGF-1 stimulation, pharmacological Akt inhibitors, siRNA knockdown of Akt, rapalog heterodimerization system for specific Akt activation, SREBP2 activation assay Biochimica et biophysica acta Medium 22005015
2013 LPS-activated TLR4-MyD88-NF-κB signaling increases SCAP expression and promotes its abnormal translocation from the ER to the Golgi, thereby activating the SCAP-SREBP2 pathway and upregulating LDLR and HMG-CoAR expression, leading to macrophage cholesterol accumulation and foam cell formation. Knockdown of MyD88 or SCAP, or blockade of IKK, each independently blocked this cross-talk. siRNA knockdown (MyD88, SCAP), IKK inhibitor, immunofluorescence/confocal microscopy for SCAP translocation, Western blot, RT-PCR, cholesterol measurement in macrophages American journal of physiology. Heart and circulatory physiology Medium 23335792
2014 Hepatic insulin receptor signaling is required for SREBP-2 induction in response to feeding and statins; liver insulin receptor knockout (LIRKO) mice show 40% decrease in Srebp-2 and 50–90% decrease in cholesterologenic genes, abolish the fasting-to-refeeding induction of SREBP-2, and lose the statin-induced SREBP-2 response. Ezetimibe (which alters intrahepatic cholesterol) restores SREBP-2 induction, suggesting insulin regulates SREBP-2 indirectly through cholesterol distribution. Liver-specific insulin receptor knockout mice, microarray, mRNA and protein expression analysis, pharmacological treatments (statins, ezetimibe) Journal of lipid research Medium 24516236
2014 Intestine-specific overexpression of active SREBP2 (driven by villin promoter in ISR2 transgenic mice) is sufficient to increase serum cholesterol in VLDL and LDL fractions and increase cholesterol and triglycerides in jejunum and liver, establishing that intestinal SREBP2 activation alone can drive hypercholesterolemia. Transgenic mouse model (villin-promoter driven active SREBP2), microarray of jejunal RNA, serum lipid and tissue lipid measurements PloS one Medium 24465397
2015 SREBP-2 deficiency in mice causes embryonic lethality with defects in limb development and expression of morphogenic genes; surviving hypomorphic mice show reduced hepatic cholesterol, lower SREBP target gene expression, and near abolishment of hepatic Srebf1c transcripts, demonstrating that SREBP-2 is required for embryonic development and regulates SREBP-1c expression in a tissue-specific manner. SREBP-2 knockout and hypomorphic mouse generation, embryo analysis, gene expression analysis (mRNA, protein) in liver and adipose tissue Journal of lipid research High 26685326
2015 FXR activation by agonists (GSK2324 or GW4064) induces Srebp-2 mRNA and precursor SREBP-2 protein via an FXR response element within intron 10 of Srebp-2, and co-induces miR-33 (suppressing ABCA1, NSF, CPT1); however, nuclear active SREBP-2 and its target genes are not induced because FXR simultaneously induces INSIG-2A, which blocks SCAP-mediated SREBP-2 processing. This uncouples miR-33 expression from mature SREBP-2 activity. FXR-dependent induction of both Srebp-2 and miR-33 requires SCAP (absent in Scap-/- mice). FXR agonist treatment, ChIP-seq (FXR response element identification), Scap-/- mice, mRNA and protein expression analysis, gene target analysis Arteriosclerosis, thrombosis, and vascular biology High 25593129
2017 CRTC2 (a transcription coactivator) regulates SREBP-2 transcription by interfering with FOXO1 recognition of insulin response element 1 (but not IRE2) in the SREBP-2 promoter, thereby inducing SREBP-2 and its target HMGCR to drive hepatic cholesterol synthesis. CRTC2 overexpression elevates liver cholesterol; SREBP-2 knockdown abolishes the CRTC2 effect on HMGCR. Adenovirus-mediated CRTC2 overexpression and CRTC2 knockout mice, in vivo HMGCR-luciferase imaging, promoter CRE/SRE mutation reporters, SREBP-2 siRNA rescue experiment Hepatology (Baltimore, Md.) Medium 28395113
2011 lop13 mice carry a spontaneous C3112T missense mutation (R1038C) in exon 18 of Srebf2, within its regulatory domain, causing nuclear cataracts, persistent skin wounds, and reduced cholesterol in brain, liver, and lens. Lack of complementation in Srebf2(lop13/GT) compound heterozygotes genetically confirms this hypomorphic Srebf2 mutation as causative, establishing Srebf2 as essential for lens and skin homeostasis. Linkage analysis, DNA sequencing, genetic complementation test (compound heterozygotes with gene-trap allele), gas chromatography for cholesterol measurement, histology Mammalian genome : official journal of the International Mammalian Genome Society High 21858719
2020 RNF5, an ER-anchored E3 ubiquitin ligase, mediates Lys-29-linked polyubiquitination of SCAP at Lys-305 (in cytosolic loop 2), which enhances the interaction between SCAP luminal loops 1 and 7 (a conformational change required for SREBP2 activation), thereby activating SREBP2 and promoting cholesterol biosynthesis. K305R SCAP variant fails to restore SREBP2 pathway in SCAP-deficient cells. RNF5 knockdown and overexpression in hepatoma cells, ubiquitination assays, mechanistic mutagenesis (K305R SCAP), interaction studies between SCAP luminal loops, rescue in SCAP-deficient cell lines The Journal of biological chemistry High 32054686
2020 SREBP2 directly induces transcription of Transferrin (TF) in melanoma circulating tumor cells, thereby reducing intracellular iron pools, reactive oxygen species, and lipid peroxidation, and conferring resistance to ferroptosis inducers. Knockdown of TF impairs tumor formation, partially rescued by lipophilic antioxidants. Single-cell RNA analysis of patient CTCs, SREBP2-driven TF transcription assay, TF knockdown, ferroptosis rescue experiments with ferrostatin-1 and vitamin E Cancer discovery Medium 33203734
2020 Caspase-3 (CASP3) mediates cleavage of SREBP2 from the endoplasmic reticulum to promote cholesterol biosynthesis in hepatocellular carcinoma (HCC) cells, driving cancer stem cell expansion and resistance to sorafenib/lenvatinib treatment via activation of the sonic hedgehog signaling pathway. Loss of SREBP2 conferred sensitivity to tyrosine kinase inhibitors. RNA sequencing of drug-resistant patient-derived xenografts, SREBP2 loss-of-function (siRNA/CRISPR), caspase-3 cleavage assay, sonic hedgehog pathway analysis, xenograft mouse models Cancer research Medium 35767704
2021 Qki-5 functions as a transcriptional co-activator of Srebp2 in oligodendrocytes to control transcription of cholesterol biosynthesis genes. Qki depletion in neural stem cells or OPCs results in impaired cholesterol biosynthesis and defective myelinogenesis (without blocking oligodendrocyte differentiation), and substantially reduces brain cholesterol concentration. Qki conditional knockout in neural stem cells or OPCs in mice, RNA-seq, cholesterol measurement, functional myelination assessment eLife Medium 33942715
2021 AAV2/5-mediated delivery of the transcriptionally active N-terminal fragment of human SREBP2 specifically to striatal astrocytes in R6/2 Huntington's disease mice activates cholesterol biosynthesis pathway genes, restores synaptic transmission, reverses Drd2 transcript decline, clears mutant huntingtin aggregates, and attenuates behavioral deficits, establishing that glial SREBP2 participates in HD brain pathogenesis. AAV2/5 gene therapy in R6/2 HD mice, electrophysiology (synaptic transmission), gene expression analysis, immunohistochemistry for huntingtin aggregates, behavioral tests Brain : a journal of neurology Medium 33974044
2022 Unspliced XBP1 (XBP1-u) colocalizes with SREBP2 and inhibits its ubiquitination/proteasomal degradation, thereby stabilizing SREBP2 and activating HMGCR transcription to promote cholesterol biosynthesis and tumorigenesis in HCC cells. Co-localization studies, ubiquitination assays, XBP1-u overexpression/knockdown, HMGCR expression analysis, tumor growth assays Cellular and molecular life sciences : CMLS Medium 35933495
2022 SREBF2 directly binds the promoter region of STARD4 (a mitochondrial cholesterol trafficking protein) to promote its transcription, increasing mitochondrial cholesterol levels and inhibiting cytochrome c release, thereby conferring sorafenib resistance in HCC. SREBF2 knockdown decreases mitochondrial cholesterol and increases cytochrome c release; STARD4 overexpression reverses SREBF2 knockdown effects. ChIP showing SREBF2 binding to STARD4 promoter, SREBF2/STARD4 siRNA knockdown, mitochondrial cholesterol measurement, cytochrome c release assay, sorafenib-resistant xenograft models Cancer science Medium 35642354
2022 USP28, a deubiquitinating enzyme, binds mature SREBP2, deubiquitinates it, and stabilizes it, thereby increasing expression of mevalonate pathway enzymes and metabolic flux. USP28 silencing reduces SREBP2 protein levels and renders cancer cells sensitive to statin treatment (rescued by geranyl-geranyl pyrophosphate). USP28 siRNA/CRISPR deletion, deubiquitination assays, co-immunoprecipitation (USP28-SREBP2 interaction), metabolic flux analysis, tissue microarray analysis, SREBP2 CRISPR KO mouse tumor model Cell death and differentiation Medium 37202505
2022 KIF11 interacts with SREBP2 protein and attenuates its ubiquitination-mediated degradation, thereby enhancing SREBP2 protein stability and accumulation and upregulating mevalonate pathway genes (HMGCR, FDFT1, SQLE, MSMO1) and free cholesterol to drive pancreatic cancer progression. Co-immunoprecipitation (KIF11-SREBP2), ubiquitination assay, SREBP2-dependent rescue experiments, xenograft mouse model Cancer medicine Low 35619540
2022 Caffeine increases hepatic ER Ca2+ levels, which blocks transcriptional activation (proteolytic processing) of SREBP2, thereby reducing PCSK9 expression and increasing LDLR expression and LDL-cholesterol clearance. ER Ca2+ is identified as a regulator of SREBP2 activation. Caffeine treatment in hepatic cells and human volunteers, ER Ca2+ measurement, SREBP2 processing assay, PCSK9 and LDLR expression analysis, analog development Nature communications Medium 35140212
2020 Endothelial HMGB1 regulates SREBP2 by prolonging its protein half-life (reducing its degradation rate); HMGB1 depletion reduces SREBP2 levels and consequently SR-BI expression, attenuating LDL transcytosis. Conversely, increased LDL causes SR-BI-dependent nuclear translocation of HMGB1. This HMGB1-SREBP2-SR-BI axis controls endothelial LDL transcytosis and atherosclerosis in vivo. siRNA knockdown in coronary artery endothelial cells, TIRF microscopy for LDL transcytosis, HMGB1 overexpression, SREBP2 half-life measurement, endothelial-specific HMGB1 KO mice, atherosclerosis assessment Arteriosclerosis, thrombosis, and vascular biology Medium 33054399
2021 SREBP2 overexpression in endothelial cells directly binds the promoter regions of mesenchymal genes (snai1, α-smooth muscle actin, vimentin, neural cadherin) and transactivates them, driving endothelial-to-mesenchymal transition. EC-specific SREBP2 transgenic mice show exacerbated vascular remodeling and mesenchymal transition after bleomycin-induced pulmonary fibrosis. SREBP2 overexpression transcriptomics, ChIP for promoter binding of mesenchymal genes, EC-specific transgenic SREBP2 mice, bleomycin pulmonary fibrosis model, epigenetic analysis JCI insight Medium 34806652
2023 PKCλ/ι (an atypical PKC) phosphorylates SCAP, promoting its degradation and thereby inhibiting SREBP2 processing and activation. PKCλ/ι deficiency in intestinal epithelial cells upregulates SREBP2 and cholesterol biosynthesis, driving mesenchymal/serrated colorectal cancer initiation. PKCλ/ι conditional knockout in intestinal epithelial cells, SCAP phosphorylation/degradation assay, SREBP2 processing assay, mouse serrated tumor model, human sample validation Nature communications Medium 38092754
2020 NBEAL1, a Golgi-associated BEACH domain protein, regulates SREBP2 processing by interacting with SCAP and PAQR3, modulating LDLR expression. Reduced NBEAL1 expression leads to downregulation of LDLR and is associated with increased coronary artery disease risk. NBEAL1 knockdown/overexpression, co-immunoprecipitation (NBEAL1-SCAP-PAQR3 interaction), SREBP2 processing assay, LDLR expression analysis, human genetic association (eQTL) Scientific reports Low 32161285
2019 SREBP2 directly binds the SRBEF2 (own gene) promoter SRE-1 element and also directly regulates SQLE gene promoter (through two newly identified SP1 and SREBF2 binding sites). OSBPL2 deletion inhibits AMPK signaling, allowing SP1 and SREBF2 to enter the nucleus and upregulate SQLE, increasing intracellular cholesterol and cholesteryl ester accumulation. CRISPR/Cas9 OSBPL2 knockout, RNA-seq, dual-luciferase reporter assay for SQLE promoter with transcription factor binding site mapping, AMPK signaling analysis Experimental cell research Medium 31356817
2019 Estrogen (E2) stimulates SREBP2 transcription in hepatic cells (HepG2, HuH-7) via a functional estrogen response element (ERE) in the SREBP2 promoter, to which ERα specifically binds; this is blocked by ERα antagonist. E2-driven SREBP2 induction increases HMGCR and LDLR expression and lipid secretion. Luciferase reporter assay with ERE and mutated ERE constructs, ChIP analysis confirming ERα binding at SREBP2 promoter, ERα antagonist treatment, RT-PCR and immunofluorescence Cellular & molecular biology letters Medium 31827541
2017 In neurons challenged with oligomeric Aβ42, SREBP2 activation is reduced because Aβ42 impairs Akt phosphorylation, which is required for SREBP2 transport from the ER to the Golgi (but does not affect enzymatic cleavage per se). Constitutively active Akt overexpression prevents Aβ42-induced SREBP2 inhibition and the downstream block of cholesterol synthesis and protein prenylation. Multiple neuronal cell types, oAβ42 treatment, Akt phosphorylation assay, SREBP2 activation assay, constitutively active Akt overexpression rescue, TgCRND8 AD mouse brain analysis Journal of lipid research Medium 29122977
2012 TGF-β induces SREBP-2 and HMGCR expression in chondrocytes via integrin αV (ITGAV) and PI3K/Akt signaling. Smad3 interacts with SREBP-2. A functional SNP (1784G>C) in SREBP-2 causes upregulation of IL-1β and MMP-13 in chondrocytes. Integrin inhibition with cyclo-RGDFV peptide downregulates SREBP-2, HMGCR, phospho-PI3K, and MMP-13 and upregulates aggrecan. TGF-β treatment of normal chondrocytes, ITGAV/PI3K/Akt pathway analysis, Smad3-SREBP-2 interaction (implied), cyclo-RGDFV peptide treatment, SREBP-2 plasmid transfection with functional readouts PloS one Low 22662110
2013 APP α-cleavage product (APPsα ectodomain) acts as a positive regulator of SREBP2 signaling in astrocytic, hepatic, and fibroblast cells, increasing SRE-dependent gene expression (~30%), cholesterol biosynthesis, and LDL receptor levels. The β-cleaved ectodomain represses SRE-dependent gene expression (~30%), establishing opposing paracrine regulators of SREBP2. In cholesterol-loaded cells (where β-cleavage dominates), this creates a feedback loop reducing cholesterol synthesis. APP cleavage product treatment in multiple human cell lines (U251MG, HepG2, fibroblasts), SRE-reporter assay, cholesterol biosynthesis and LDLR measurement, β-cleavage inhibitor experiments, patient fibroblast analysis FASEB journal : official publication of the Federation of American Societies for Experimental Biology Medium 24249638
2021 SREBP2 directly binds the promoter region of YAP and transactivates it; uric acid/monosodium urate-induced SREBP2 in endothelial cells drives YAP signaling and pro-inflammatory gene expression. SREBP2 siRNA knockdown partially abolishes UA/MSU-induced YAP activity and monocyte adhesion; endothelial SREBP2 transgenic mice show activated YAP signaling. SREBP2 siRNA, adenovirus-SREBP2 overexpression with RNA-seq, SREBP2 endothelial transgenic mice, pharmacological SREBP2 inhibitor (betulin), promoter binding assay (implied), hyperuricemia mouse model FASEB journal : official publication of the Federation of American Societies for Experimental Biology Medium 33977576
2024 Melanoma-derived lactate activates SREBP2 in tumor-infiltrating conventional dendritic cells, driving their transformation into mature regulatory DCs (mregDCs) via the mevalonate biosynthetic pathway. DC-specific genetic silencing or pharmacologic inhibition of SREBP2 promoted antitumor CD8+ T cell activation and suppressed melanoma progression. CD63 was identified as a surface marker for mregDCs. DC-specific SREBP2 genetic silencing, pharmacological SREBP2 inhibition, transcriptional and metabolic studies, lactate treatment of DCs, T cell activation assays, in vivo melanoma models, human sentinel lymph node analysis Science immunology Medium 38728412
2024 ALOX15B-mediated lipid peroxidation activates ERK1/2 in macrophages, which in turn increases SREBP2 nuclear abundance and activity, controlling cholesterol biosynthesis. ALOX15B silencing reduces ERK1/2 activation and nuclear SREBP2, suppressing sterol biosynthetic intermediates (desmosterol, lathosterol) and making macrophages refractory to NPC1 inhibition-induced SREBP2 activation. ALOX15B siRNA in primary human macrophages, global transcriptome analysis, immunofluorescence for nuclear SREBP2, ERK1/2 inhibition, sterol biosynthetic intermediate measurement by mass spectrometry Redox biology Medium 38581859
2021 SNX10 (sorting nexin 10) interacts with SCAP, and SNX10 deletion promotes dissociation of ERLIN2 from SCAP, enhancing SREBP2 activation and increasing intracellular cholesterol biosynthesis in intestinal stem cells, promoting their stemness. SNX10 conditional knockout in intestinal epithelial cells or ISCs promotes mucosal repair. SNX10 conditional knockout mice, ERLIN2-SCAP interaction analysis, SREBP2 activation assay, intracellular cholesterol measurement, ISC stemness assays, SNX10 small-molecule inhibitor (DC-SX029) Science advances Medium 37647408
2025 Nuclear SREBP2 (nSREBP2) forms phase-separated condensates in the nucleus through its amino-terminal intrinsically disordered region (IDR). These condensates co-localize with transcription coactivators, partly on superenhancers, to activate lipogenic gene transcription. A conserved phenylalanine-to-alanine substitution in the IDR abolishes condensate formation and reduces transcriptional activity; fusion with a phase-separation-driving FUS-IDR rescues activity. Knock-in of this mutation in male mice impairs feeding-induced nSREBP2 activity and lowers hepatic and circulating cholesterol. Phase separation assays (condensate formation), IDR mutagenesis (Phe→Ala), FUS-IDR fusion rescue, ChIP-seq on superenhancers, knock-in mouse model, cholesterol measurement in vivo Nature metabolism High 40394324
2021 LPS increases SREBF2 expression via the TLR4/JNK/c-Jun signaling pathway, and simultaneously suppresses UBE2I-mediated SREBF2 sumoylation to enhance its transcriptional activity, resulting in increased intracellular cholesterol and ER stress (Bax upregulation) in portal vein endothelial cells. LPS treatment of endothelial cells, TLR4/JNK/c-Jun pathway analysis, sumoylation assay (UBE2I knockdown), SREBF2 expression and transcriptional activity assays, ER stress markers Cell biology and toxicology Low 33677747
2023 Parkin expression level positively correlates with neuronal lipoprotein lipase (LPL) protein level and activity through SREBP2 as mediator; SREBP2 genetic ablation abolishes Parkin's effect on LPL expression. The Parkin-SREBP2-LPL pathway regulates intracellular lipid droplet formation and is upregulated by PD-linked oxidative stress (rotenone). Human neuroblastoma cell line and Parkin knockout mouse model, LPL activity assay, SREBP2 genetic ablation, lipid droplet assay, rotenone oxidative stress treatment Human molecular genetics Medium 36519761
2020 SREBP2 directly regulates LDLR transcription by binding its promoter; SREBP2 also indirectly regulates LDLR by increasing transcription of lncRNA LDLR-AS in fish hepatocytes. LDLR-AS functions as an RNA scaffold recruiting hnRNPR to the 5′ UTR of LDLR mRNA, stabilizing LDLR mRNA post-transcriptionally. SREBP2 knockdown, ChIP/reporter assay for LDLR promoter binding, LDLR-AS knockdown, RNA immunoprecipitation for hnRNPR binding, mRNA stability assay, triglyceride accumulation measurement (fish model) iScience Low 35811843
2021 SREBP2 binds to the promoter region of NLRC4 and activates its transcription in keratinocytes; LCN2 signaling through SREBP2 drives NLRC4-mediated inflammation in psoriasis. Suppressing SREBP2 in mice attenuated NLRC4 signaling and psoriasis-like dermatitis. ChIP showing SREBP2 binding to NLRC4 promoter, SREBP2 knockdown in mice, LCN2/24p3R silencing in psoriasis mouse model, in vitro keratinocyte assays The Journal of investigative dermatology Medium 35120997
2022 ZIKV infection increases recruitment of SREBP2 transcription factors to lipid gene promoters; pharmacological inhibition or genetic silencing of SREBP2 suppresses ZIKV infection of human dendritic cells, establishing SREBP2-activated lipid gene transcription as a mechanism exploited for viral replication. Genomics profiling of ZIKV-infected vs uninfected primary human DCs, ChIP for SREBP2 at lipid gene promoters, pharmacological SREBP2 inhibition, SREBP2 siRNA knockdown, ZIKV infectivity assays Nature communications Medium 36097162
2018 SREBP-2 pathway activity is required for the cytotoxicity of C. difficile toxins A and B; SREBP-2 regulates membrane cholesterol content, which is necessary for toxin pore formation in endosomal membranes and translocation of the glucosyltransferase domain. Pharmacological SREBP-2 pathway inhibition (PF-429242, 25-hydroxycholesterol, simvastatin) or SREBP-2 pathway-deficient cells protected against toxin intoxication; this protection was bypassed when the toxin's enzyme domain was delivered independently of pore formation. SREBP-2 pathway inhibitors (pharmacological and genetic), toxin B pore formation assay, anthrax protective antigen-mediated enzyme delivery (mechanistic bypass), cell viability assays FASEB journal : official publication of the Federation of American Societies for Experimental Biology Medium 30592645
2019 Elaidate (industrial trans fatty acid) activates SREBP2 via the SCAP-SREBP2 axis in hepatocytes by lowering intracellular free cholesterol levels, inducing cholesterol biosynthesis. This effect is SCAP-dependent but independent of liver-X receptor and UBXD8. Exogenous cholesterol represses, and elaidate attenuates, this anti-cholesterogenic feedback. Transcriptomics of hepatoma cells treated with elaidate vs oleate/palmitate, SCAP-dependent knockdown experiments, intracellular free cholesterol measurement, SREBP2 activity assay, diet-fed mouse model Molecular nutrition & food research Medium 31327168
2008 In MFP2 (multifunctional protein 2, peroxisomal β-oxidation) knockout mice, PPAR-α activation by endogenous ligands (from accumulated peroxisomal substrates) leads to upregulation of SREBP2 and HMGCR; in MFP2/PPAR-α double knockout mice, SREBP2 and HMGCR upregulations are markedly attenuated, demonstrating a PPAR-α-dependent pathway for SREBP2 induction. MFP2 KO and MFP2/PPARα double KO mice, real-time PCR, gene expression profiling, cholesterol biosynthesis rate measurement Biochimica et biophysica acta Medium 18773970
2016 Irisin activates AMPK in hepatocytes, which inhibits SREBP2 transcription and nuclear translocation, reducing hepatic cholesterol synthesis. AMPKα1 siRNA or compound C (AMPK inhibitor) blocks irisin-induced changes in SREBP2 and cholesterol levels, establishing AMPK as a required mediator between irisin and SREBP2. Irisin infusion in DIO mice, primary hepatocyte treatment, AMPK activation/inhibition (compound C, AMPKα1 siRNA), SREBP2 nuclear translocation assay, cholesterol measurement EBioMedicine Medium 27211556
2020 SREBP2 directly induces transcription of PCSK9 via the sterol regulatory element in its promoter; caffeine blocks this by increasing ER Ca2+. PXR activation increases proteolytic activation of SREBP2 (SCAP-mediated), driving widespread induction of cholesterol synthesis genes and PCSK9 in mice and humans. PXR ligand (rifampicin) treatment in humans and mice, NMR metabolomics, PXR KO mice, cholesterol synthesis intermediate measurement (lathosterol ratio), PCSK9 plasma measurement British journal of pharmacology Medium 33687065

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 miR-33 links SREBP-2 induction to repression of sterol transporters. Proceedings of the National Academy of Sciences of the United States of America 468 20566875
2010 Expression of miR-33 from an SREBP2 intron inhibits cholesterol export and fatty acid oxidation. The Journal of biological chemistry 304 20732877
2009 Enhanced free cholesterol, SREBP-2 and StAR expression in human NASH. Journal of hepatology 293 19231010
1995 Structure of the human gene encoding sterol regulatory element binding protein-1 (SREBF1) and localization of SREBF1 and SREBF2 to chromosomes 17p11.2 and 22q13. Genomics 237 7759101
2020 The Lipogenic Regulator SREBP2 Induces Transferrin in Circulating Melanoma Cells and Suppresses Ferroptosis. Cancer discovery 202 33203734
2004 ATF6 modulates SREBP2-mediated lipogenesis. The EMBO journal 182 14765107
2016 Novel osmotin inhibits SREBP2 via the AdipoR1/AMPK/SIRT1 pathway to improve Alzheimer's disease neuropathological deficits. Molecular psychiatry 173 27001618
2007 ABCG1 and ABCG4 are coexpressed in neurons and astrocytes of the CNS and regulate cholesterol homeostasis through SREBP-2. Journal of lipid research 132 17916878
2016 Irisin Inhibits Hepatic Cholesterol Synthesis via AMPK-SREBP2 Signaling. EBioMedicine 115 27211556
2020 COVID-19-activated SREBP2 disturbs cholesterol biosynthesis and leads to cytokine storm. Signal transduction and targeted therapy 112 32883951
2024 A lactate-SREBP2 signaling axis drives tolerogenic dendritic cell maturation and promotes cancer progression. Science immunology 101 38728412
2022 Caspase-3-Induced Activation of SREBP2 Drives Drug Resistance via Promotion of Cholesterol Biosynthesis in Hepatocellular Carcinoma. Cancer research 98 35767704
1997 Structure of the human gene encoding sterol regulatory element binding protein 2 (SREBF2). Genomics 91 9070916
2006 ABCA7 expression is regulated by cellular cholesterol through the SREBP2 pathway and associated with phagocytosis. Journal of lipid research 89 16788211
2022 Caffeine blocks SREBP2-induced hepatic PCSK9 expression to enhance LDLR-mediated cholesterol clearance. Nature communications 82 35140212
2022 Gut flora disequilibrium promotes the initiation of liver cancer by modulating tryptophan metabolism and up-regulating SREBP2. Proceedings of the National Academy of Sciences of the United States of America 79 36534812
2011 Regulation of lipid homeostasis by the bifunctional SREBF2-miR33a locus. Cell metabolism 69 21356514
2011 Akt acutely activates the cholesterogenic transcription factor SREBP-2. Biochimica et biophysica acta 65 22005015
2015 SREBP-2-deficient and hypomorphic mice reveal roles for SREBP-2 in embryonic development and SREBP-1c expression. Journal of lipid research 59 26685326
2009 Serum cholesterol and expression of ApoAI, LXRbeta and SREBP2 in vitamin D receptor knock-out mice. The Journal of steroid biochemistry and molecular biology 55 19429425
2008 Polymorphisms in SREBF1 and SREBF2, two antipsychotic-activated transcription factors controlling cellular lipogenesis, are associated with schizophrenia in German and Scandinavian samples. Molecular psychiatry 54 18936756
2018 Metformin treatment prevents SREBP2-mediated cholesterol uptake and improves lipid homeostasis during oxidative stress-induced atherosclerosis. Free radical biology & medicine 52 29499335
2013 Cross-talk between TLR4-MyD88-NF-κB and SCAP-SREBP2 pathways mediates macrophage foam cell formation. American journal of physiology. Heart and circulatory physiology 52 23335792
2012 Central role of SREBP-2 in the pathogenesis of osteoarthritis. PloS one 51 22662110
2022 Matrine suppresses NLRP3 inflammasome activation via regulating PTPN2/JNK/SREBP2 pathway in sepsis. Phytomedicine : international journal of phytotherapy and phytopharmacology 47 36610161
2021 Activation of pregnane X receptor induces atherogenic lipids and PCSK9 by a SREBP2-mediated mechanism. British journal of pharmacology 47 33687065
2020 Dual targeting of SREBP2 and ERRα by carnosic acid suppresses RANKL-mediated osteoclastogenesis and prevents ovariectomy-induced bone loss. Cell death and differentiation 47 31907393
2018 SREBP2 contributes to cisplatin resistance in ovarian cancer cells. Experimental biology and medicine (Maywood, N.J.) 44 29466876
2010 HNF1alpha and SREBP2 are important regulators of NPC1L1 in human liver. Journal of lipid research 44 20460578
2021 Role of endothelial cells in pulmonary fibrosis via SREBP2 activation. JCI insight 42 34806652
2020 Endothelial HMGB1 Is a Critical Regulator of LDL Transcytosis via an SREBP2-SR-BI Axis. Arteriosclerosis, thrombosis, and vascular biology 39 33054399
2020 Diallyl disulfide improves lipid metabolism by inhibiting PCSK9 expression and increasing LDL uptake via PI3K/Akt-SREBP2 pathway in HepG2 cells. Nutrition, metabolism, and cardiovascular diseases : NMCD 38 33500108
2019 Industrial Trans Fatty Acids Stimulate SREBP2-Mediated Cholesterogenesis and Promote Non-Alcoholic Fatty Liver Disease. Molecular nutrition & food research 37 31327168
2022 LCN2 Mediates Skin Inflammation in Psoriasis through the SREBP2‒NLRC4 Axis. The Journal of investigative dermatology 36 35120997
2022 SREBP2-dependent lipid gene transcription enhances the infection of human dendritic cells by Zika virus. Nature communications 36 36097162
2019 LncRNA SNHG16 induces the SREBP2 to promote lipogenesis and enhance the progression of pancreatic cancer. Future oncology (London, England) 36 31664866
2017 A novel role for CRTC2 in hepatic cholesterol synthesis through SREBP-2. Hepatology (Baltimore, Md.) 36 28395113
2021 SREBP2 gene therapy targeting striatal astrocytes ameliorates Huntington's disease phenotypes. Brain : a journal of neurology 35 33974044
2014 Hepatic insulin receptor deficiency impairs the SREBP-2 response to feeding and statins. Journal of lipid research 34 24516236
2008 Coordinate induction of PPAR alpha and SREBP2 in multifunctional protein 2 deficient mice. Biochimica et biophysica acta 34 18773970
2022 Unspliced XBP1 contributes to cholesterol biosynthesis and tumorigenesis by stabilizing SREBP2 in hepatocellular carcinoma. Cellular and molecular life sciences : CMLS 32 35933495
2008 Rapamycin down-regulates LDL-receptor expression independently of SREBP-2. Biochemical and biophysical research communications 32 18602894
2023 Artesunate induces ferroptosis by inhibiting the nuclear localization of SREBP2 in myeloma cells. International journal of medical sciences 31 37859702
2022 SREBF2-STARD4 axis confers sorafenib resistance in hepatocellular carcinoma by regulating mitochondrial cholesterol homeostasis. Cancer science 31 35642354
2018 Diabetes Mellitus in Pregnancy Leads to Growth Restriction and Epigenetic Modification of the Srebf2 Gene in Rat Fetuses. Hypertension (Dallas, Tex. : 1979) 31 29610268
2020 Ring finger protein 5 activates sterol regulatory element-binding protein 2 (SREBP2) to promote cholesterol biosynthesis via inducing polyubiquitination of SREBP chaperone SCAP. The Journal of biological chemistry 30 32054686
2019 OSBPL2 deficiency upregulate SQLE expression increasing intracellular cholesterol and cholesteryl ester by AMPK/SP1 and SREBF2 signalling pathway. Experimental cell research 30 31356817
2014 Overactivation of intestinal SREBP2 in mice increases serum cholesterol. PloS one 30 24465397
2015 The Flavone Luteolin Suppresses SREBP-2 Expression and Post-Translational Activation in Hepatic Cells. PloS one 29 26302339
2014 Expression of miR-33 from an SREBF2 intron targets the FTO gene in the chicken. PloS one 29 24626192
2014 Oxysterols synergize with statins by inhibiting SREBP-2 in ovarian cancer cells. Gynecologic oncology 29 25134999
2024 Cholesterol homeostasis confers glioma malignancy triggered by hnRNPA2B1-dependent regulation of SREBP2 and LDLR. Neuro-oncology 28 38070488
2023 USP28 controls SREBP2 and the mevalonate pathway to drive tumour growth in squamous cancer. Cell death and differentiation 28 37202505
2023 Enhanced SREBP2-driven cholesterol biosynthesis by PKCλ/ι deficiency in intestinal epithelial cells promotes aggressive serrated tumorigenesis. Nature communications 27 38092754
2020 The miR-28-5p Targetome Discovery Identified SREBF2 as One of the Mediators of the miR-28-5p Tumor Suppressor Activity in Prostate Cancer Cells. Cells 27 32028704
2020 NBEAL1 controls SREBP2 processing and cholesterol metabolism and is a susceptibility locus for coronary artery disease. Scientific reports 27 32161285
2023 Loss of hepatic FTCD promotes lipid accumulation and hepatocarcinogenesis by upregulating PPARγ and SREBP2. JHEP reports : innovation in hepatology 26 37675273
2021 Qki regulates myelinogenesis through Srebp2-dependent cholesterol biosynthesis. eLife 26 33942715
2017 Induction of Lipin1 by ROS-Dependent SREBP-2 Activation. Toxicological research 26 28744353
2015 The nuclear receptor FXR uncouples the actions of miR-33 from SREBP-2. Arteriosclerosis, thrombosis, and vascular biology 26 25593129
2024 ALOX15B controls macrophage cholesterol homeostasis via lipid peroxidation, ERK1/2 and SREBP2. Redox biology 25 38581859
2017 Aβ inhibits SREBP-2 activation through Akt inhibition. Journal of lipid research 25 29122977
2023 Inhibiting sorting nexin 10 promotes mucosal healing through SREBP2-mediated stemness restoration of intestinal stem cells. Science advances 24 37647408
2022 Butyrate Lowers Cellular Cholesterol through HDAC Inhibition and Impaired SREBP-2 Signalling. International journal of molecular sciences 24 36555149
2007 Guar gum consumption increases hepatic nuclear SREBP2 and LDL receptor expression in pigs fed an atherogenic diet. The Journal of nutrition 24 17311941
2022 KIF11 manipulates SREBP2-dependent mevalonate cross talk to promote tumor progression in pancreatic ductal adenocarcinoma. Cancer medicine 23 35619540
2022 Increased LDL receptor by SREBP2 or SREBP2-induced lncRNA LDLR-AS promotes triglyceride accumulation in fish. iScience 23 35811843
2022 SREBP2 promotes the viability, proliferation, and migration and inhibits apoptosis in TGF-β1-induced airway smooth muscle cells by regulating TLR2/NF-κB/NFATc1/ABCA1 regulatory network. Bioengineered 22 35037821
2015 MicroRNA-185-5p mediates regulation of SREBP2 expression by hepatitis C virus core protein. World journal of gastroenterology 22 25914460
2023 ABCA9, an ER cholesterol transporter, inhibits breast cancer cell proliferation via SREBP-2 signaling. Cancer science 21 36576228
2013 Amyloid precursor protein α- and β-cleaved ectodomains exert opposing control of cholesterol homeostasis via SREBP2. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 21 24249638
2024 LINC00618 facilitates growth and metastasis of hepatocellular carcinoma via elevating cholesterol synthesis by promoting NSUN2-mediated SREBP2 m5C modification. Ecotoxicology and environmental safety 20 39299205
2019 SREBP2 is upregulated in esophageal squamous cell carcinoma and co‑operates with c‑Myc to regulate HMGCR expression. Molecular medicine reports 19 31432128
2014 Association between SREBF2 gene polymorphisms and metabolic syndrome in clozapine-treated patients with schizophrenia. Progress in neuro-psychopharmacology & biological psychiatry 19 25201120
2005 Analysis of the SREBF2 gene as a genetic risk factor for vascular dementia. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 19 16082694
2023 Chlorogenic acid regulates the expression of NPC1L1 and HMGCR through PXR and SREBP2 signaling pathways and their interactions with HSP90 to maintain cholesterol homeostasis. Phytomedicine : international journal of phytotherapy and phytopharmacology 18 38103317
2021 Gout-induced endothelial impairment: The role of SREBP2 transactivation of YAP. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 33977576
2020 Rspo1/Rspo3-LGR4 signaling inhibits hepatic cholesterol synthesis through the AMPKα-SREBP2 pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 32926477
2024 Influenza A virus infection activates STAT3 to enhance SREBP2 expression, cholesterol biosynthesis, and virus replication. iScience 17 39108727
2019 Estrogen stimulates SREBP2 expression in hepatic cell lines via an estrogen response element in the SREBP2 promoter. Cellular & molecular biology letters 17 31827541
2016 Genistein upregulates LDLR levels via JNK-mediated activation of SREBP-2. Food & nutrition research 17 27211318
2024 Fatostatin promotes anti-tumor immunity by reducing SREBP2 mediated cholesterol metabolism in tumor-infiltrating T lymphocytes. European journal of pharmacology 16 38522641
2021 Knocking down Sterol regulatory element binding protein 2 (SREBF2) inhibits the Serine Protease 8 (PRSS8) /sodium channel epithelial 1alpha subunit (SCNN1A) axis to reduce the cell proliferation, migration and epithelial-mesenchymal transformation of ovarian cancer. Bioengineered 16 34823420
2018 Cytotoxicity of Clostridium difficile toxins A and B requires an active and functional SREBP-2 pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 16 30592645
2024 Gypenoside L inhibits hepatocellular carcinoma by targeting the SREBP2-HMGCS1 axis and enhancing immune response. Bioorganic chemistry 15 38861912
2023 SREBP2 inhibitor betulin sensitizes hepatocellular carcinoma to lenvatinib by inhibiting the mTOR/IL-1β pathway. Acta biochimica et biophysica Sinica 15 37434430
2022 LncCCAT1 interaction protein PKM2 upregulates SREBP2 phosphorylation to promote osteosarcoma tumorigenesis by enhancing the Warburg effect and lipogenesis. International journal of oncology 15 35244192
2019 Selective Ah receptor modulators attenuate NPC1L1-mediated cholesterol uptake through repression of SREBP-2 transcriptional activity. Laboratory investigation; a journal of technical methods and pathology 15 31417158
2018 SREBP-2, a new target of metformin? Drug design, development and therapy 15 30584280
2022 The elevation of miR-185-5p alleviates high-fat diet-induced atherosclerosis and lipid accumulation in vivo and in vitro via SREBP2 activation. Aging 14 35172278
2020 Regulatory Roles of SREBF1 and SREBF2 in Lipid Metabolism and Deposition in Two Chinese Representative Fat-Tailed Sheep Breeds. Animals : an open access journal from MDPI 14 32751718
2024 Hawthorn leaf flavonoids alleviate the deterioration of atherosclerosis by inhibiting SCAP-SREBP2-LDLR pathway through sPLA2-ⅡA signaling in macrophages in mice. Journal of ethnopharmacology 13 38442806
2022 Tilianin improves lipid profile and alleviates atherosclerosis in ApoE-/- mice through up-regulation of SREBP2-mediated LDLR expression. Phytomedicine : international journal of phytotherapy and phytopharmacology 13 36610166
2020 Expression of SREBP2 and cholesterol metabolism related genes in TCGA glioma cohorts. Medicine 13 32195924
2025 Cholesterol Metabolism in CNS Diseases: The Potential of SREBP2 and LXR as Therapeutic Targets. Molecular neurobiology 12 39775479
2023 Parkin regulates neuronal lipid homeostasis through SREBP2-lipoprotein lipase pathway-implications for Parkinson's disease. Human molecular genetics 12 36519761
2023 The RORɣ/SREBP2 pathway is a master regulator of cholesterol metabolism and serves as potential therapeutic target in t(4;11) leukemia. Oncogene 12 38030791
2011 A spontaneous mutation in Srebf2 leads to cataracts and persistent skin wounds in the lens opacity 13 (lop13) mouse. Mammalian genome : official journal of the International Mammalian Genome Society 12 21858719
2025 Nuclear SREBP2 condensates regulate the transcriptional activation of lipogenic genes and cholesterol homeostasis. Nature metabolism 11 40394324
2021 SREBF2 triggers endoplasmic reticulum stress and Bax dysregulation to promote lipopolysaccharide-induced endothelial cell injury. Cell biology and toxicology 11 33677747

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