Affinage

SREBF2

Sterol regulatory element-binding protein 2 · UniProt Q12772

Length
1141 aa
Mass
123.7 kDa
Annotated
2026-04-28
100 papers in source corpus 40 papers cited in narrative 40 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SREBF2 encodes SREBP-2, a master transcriptional regulator of cholesterol homeostasis that functions as an ER-anchored bHLH-Zip transcription factor; upon sterol depletion, it undergoes sequential proteolytic cleavages—a sterol-regulated site-1 cleavage in the ER lumenal loop and a sterol-independent site-2 cleavage within the first transmembrane domain—to release an N-terminal fragment that translocates to the nucleus and binds SRE-1 elements to activate cholesterol biosynthesis (HMGCR, HMGCS1), uptake (LDLR, NPC1L1), and auxiliary metabolic genes (IDH1, ACSL1, PCSK9) (PMID:7903453, PMID:8674110, PMID:20460578, PMID:26728456). SREBP-2 processing is controlled by multiple upstream inputs including SCAP conformation (regulated by RNF5-mediated K29-linked ubiquitination at SCAP K305 and PKCλ/ι-mediated SCAP phosphorylation/degradation), ER calcium levels, insulin receptor signaling, and NF-κB–STARD10-dependent accessible cholesterol sensing (PMID:32054686, PMID:38092754, PMID:35140212, PMID:24516236, PMID:35959888); nuclear SREBP-2 activity is further modulated by PP2A-dependent dephosphorylation that promotes DNA binding, ITCH-mediated ubiquitination driving degradation, USP28-mediated deubiquitination conferring stabilization, ATF6-HDAC1 complex recruitment that represses transcription, and epigenetic silencing of the SREBF2 locus by the FoxO3–Sirt6 axis (PMID:24770487, PMID:25777360, PMID:37202505, PMID:14765107, PMID:23881913). Beyond canonical lipid metabolism, SREBP-2 co-activates cholesterol biosynthesis genes with Quaking (Qki) to support myelination and lens transparency, its intronic miR-33a coordinately suppresses cholesterol efflux via ABCA1, and in context-dependent settings it transactivates non-canonical targets including c-Myc, Transferrin, mesenchymal genes, NLRC4, and YAP effectors, linking it to cancer stemness, ferroptosis resistance, endothelial-to-mesenchymal transition, inflammasome activation, and immunomodulation in dendritic cells (PMID:34021134, PMID:33942715, PMID:20732877, PMID:26883200, PMID:33203734, PMID:34806652, PMID:35120997, PMID:38728412).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1993 High

    The identity of SREBP-2 as a bHLH-Zip transcription factor that binds SRE-1 elements and activates cholesterol-related gene transcription was established, answering the fundamental question of what protein mediates sterol-responsive transcription.

    Evidence cDNA cloning with in vitro DNA-binding and cotransfection reporter assays in HEK293 cells

    PMID:7903453

    Open questions at the time
    • Mechanism of ER-to-nucleus release unknown
    • In vivo target gene repertoire undefined
    • Relationship to SREBP-1 isoform unclear
  2. 1996 High

    The two-step proteolytic cleavage mechanism was resolved—a sterol-regulated first cleavage in the ER lumenal loop and a sterol-independent second cleavage within the transmembrane domain—explaining how SREBP-2 is liberated from the ER membrane to enter the nucleus.

    Evidence H-Ras–SREBP-2 fusion proteins, mutant CHO cell lines, cell fractionation, and transcriptional reporters

    PMID:8674110

    Open questions at the time
    • Identity of site-1 and site-2 proteases not yet determined in this study
    • SCAP chaperone mechanism not yet linked
  3. 1997 High

    Genomic characterization of SREBF2 revealed a promoter SRE-1 element, establishing a feed-forward autoregulatory loop for SREBP-2 transcription in response to sterol depletion.

    Evidence Genomic cloning, sequencing, and 5'-flanking region analysis

    PMID:9070916

    Open questions at the time
    • Quantitative contribution of autoregulation to SREBP-2 protein levels in vivo uncharacterized
  4. 2003 High

    SREBP-2's direct target repertoire was expanded beyond cholesterol/LDL genes to include IDH1, linking sterol-regulated transcription to NADPH supply for biosynthetic pathways.

    Evidence EMSA demonstrating direct SRE binding in the IDH1 promoter, mutagenesis, promoter-reporter assays

    PMID:12923220

    Open questions at the time
    • Metabolic flux consequences of SREBP-2-driven NADPH generation not measured
  5. 2004 High

    A mechanism for cross-talk between ER stress and lipogenesis was revealed: ATF6 directly binds nuclear SREBP-2 and recruits HDAC1 to SRE-bound promoters, attenuating SREBP-2 transcriptional output.

    Evidence GST pull-down, co-immunoprecipitation, ChIP, and reporter assays in liver cells

    PMID:14765107

    Open questions at the time
    • Whether ATF6-SREBP-2 interaction occurs in non-hepatic tissues unknown
    • Structural basis of leucine-zipper interaction unresolved
  6. 2009 Medium

    SREBP-2 was shown to directly bind the CASP7 promoter, extending its transcriptional reach to apoptotic machinery and raising the question of non-metabolic SREBP-2 functions.

    Evidence ChIP and siRNA knockdown with qPCR/Western blot readouts

    PMID:19323650

    Open questions at the time
    • Functional consequence of SREBP-2-driven caspase-7 expression for apoptosis not fully tested
    • Single-lab finding
  7. 2010 High

    The discovery of intronic miR-33a within SREBF2 revealed a coordinated genetic program: while SREBP-2 protein activates cholesterol synthesis, the co-transcribed miRNA suppresses cholesterol efflux (ABCA1) and fatty acid oxidation, maximizing intracellular cholesterol retention.

    Evidence miRNA identification within SREBF2 intron 16, transfection-based translation inhibition, cholesterol export, and fatty acid oxidation functional assays

    PMID:20732877

    Open questions at the time
    • Tissue-specific regulation of miR-33a processing relative to SREBP-2 mRNA not addressed
    • Therapeutic targeting of miR-33a vs. SREBP-2 not distinguished
  8. 2010 High

    NPC1L1 was established as a direct SREBP-2 transcriptional target, explaining how cholesterol absorption is coordinately upregulated with biosynthesis during sterol depletion.

    Evidence ChIP confirming in vivo SREBP-2 binding to NPC1L1 promoter, luciferase reporter, SREBP-2 overexpression rescue, human liver biopsy correlation

    PMID:20460578

    Open questions at the time
    • Relative contribution of SREBP-2 vs. other factors to NPC1L1 regulation in intestine not quantified
  9. 2013 High

    An epigenetic brake on SREBP-2 was identified: FoxO3 recruits the deacetylase Sirt6 to the SREBF2 promoter, establishing repressive chromatin (deacetylated H3K9/H3K56) and reducing hepatic cholesterol biosynthesis—connecting nutrient sensing to SREBP-2 transcriptional silencing.

    Evidence Hepatic Sirt6 knockout mice, ChIP for H3 acetylation marks, in vivo overexpression rescue in obese mice

    PMID:23881913

    Open questions at the time
    • Whether FoxO3-Sirt6 axis operates in extrahepatic tissues unknown
    • Kinetics of chromatin remodeling at the SREBF2 locus uncharacterized
  10. 2014 High

    A post-translational activation mechanism for nuclear SREBP-2 was uncovered: PP2A physically interacts with and dephosphorylates nuclear SREBP-2 upon cholesterol depletion, enhancing its DNA-binding capacity independently of proteolytic processing or nuclear import.

    Evidence Co-immunoprecipitation, ChIP, okadaic acid inhibition, PP2A siRNA, LDL uptake assays

    PMID:24770487

    Open questions at the time
    • Specific phosphorylation sites on SREBP-2 regulated by PP2A not mapped
    • Kinase counteracting PP2A on SREBP-2 not identified
  11. 2014 High

    Hepatic insulin receptor signaling was shown to be required for SREBP-2 activation in response to feeding and statin treatment, placing insulin upstream of SREBP-2 processing in liver and explaining metabolic syndrome-associated cholesterol dysregulation.

    Evidence Liver insulin receptor knockout mice (LIRKO), microarray, statin and ezetimibe epistasis

    PMID:24516236

    Open questions at the time
    • Molecular step at which insulin receptor signaling intersects SCAP-SREBP-2 not defined
  12. 2015 High

    Multiple layers of SREBP-2 regulation were defined in parallel: ITCH-mediated ubiquitination promotes SREBP-2 degradation; FXR transcriptionally induces SREBF2 yet simultaneously blocks processing via INSIG-2A; ERBB4–PI3K–mTORC1/2 signaling stimulates SREBP-2 cleavage; and SREBP-2 knockout is embryonic lethal while hypomorphic mice reveal SREBP-2 is required for hepatic SREBF1c expression.

    Evidence ApoE−/−ITCH−/− mice with ubiquitination assays; FXR ChIP-seq with Scap−/− epistasis; ERBB4 signaling with S1P inhibitor epistasis; SREBP-2 KO/hypomorph mouse models

    PMID:25593129 PMID:25777360 PMID:26535009 PMID:26685326

    Open questions at the time
    • Specific ubiquitin chain types on SREBP-2 from ITCH not characterized
    • How FXR-induced miR-33a vs. INSIG-2A balance is achieved in different nutritional states unknown
    • Developmental cause of SREBP-2 null embryonic lethality unresolved
  13. 2015 Medium

    SREBP-2 was linked to non-canonical transcriptional targets in cancer: it directly binds and activates the c-Myc promoter, inducing cancer stem cell-like properties in prostate cancer.

    Evidence ChIP, promoter reporter, SREBP-2 overexpression/knockdown, xenograft model

    PMID:26883200

    Open questions at the time
    • Whether c-Myc transactivation by SREBP-2 occurs in non-cancer contexts not tested
    • Single-lab finding
  14. 2016 High

    SREBP-2 directly activates ACSL1 transcription via a specific SRE, connecting cholesterol-sensing transcription to long-chain fatty acid activation and broadening SREBP-2's role in integrating lipid metabolism.

    Evidence EMSA with SRE mutagenesis, reporter assay, SREBP-2 siRNA in HepG2, statin treatment in hamsters and mice

    PMID:26728456

    Open questions at the time
    • Functional metabolic flux consequences of ACSL1 regulation by SREBP-2 not quantified
  15. 2020 High

    The mechanism by which SCAP conformation is regulated was advanced: RNF5-mediated K29-linked polyubiquitination of SCAP at K305 enhances SCAP luminal loop 1–loop 7 interaction, a conformational change that activates SCAP-SREBP-2 transport and processing.

    Evidence RNF5 overexpression/knockdown, K305R SCAP mutant in SCAP-deficient cells, ubiquitination assays, co-immunoprecipitation

    PMID:32054686

    Open questions at the time
    • Whether RNF5 activity on SCAP is sterol-regulated not determined
    • Structural details of how K29-ubiquitin chains alter SCAP conformation lacking
  16. 2020 Medium

    SREBP-2 was shown to directly transactivate Transferrin in circulating tumor cells, suppressing ferroptosis by reducing iron and lipid peroxidation—establishing a non-canonical anti-ferroptotic function.

    Evidence scRNA-seq of CTCs, SREBP-2/TF knockdown, ferroptosis induction, lipid peroxidation measurement, xenograft

    PMID:33203734

    Open questions at the time
    • Direct SREBP-2 binding to TF promoter not shown by ChIP
    • Generalizability beyond melanoma CTCs untested
  17. 2021 High

    Quaking (Qki) was identified as a transcriptional co-activator of SREBP-2 that co-recruits SREBP-2 and RNA Pol II to cholesterol biosynthesis gene promoters in the lens and oligodendrocytes, explaining why Qki loss causes cataracts and hypomyelination despite normal SREBP-2 levels.

    Evidence Lens-specific and NSC/OPC-specific conditional Qki KO mice, ChIP for SREBP-2 and Pol II, cholesterol measurement, sterol rescue

    PMID:33942715 PMID:34021134

    Open questions at the time
    • Whether Qki-SREBP-2 interaction is direct or mediated by additional factors not fully resolved
    • Tissue-specific co-activator requirements in other SREBP-2-dependent cell types unexplored
  18. 2021 High

    A 25-hydroxycholesterol–SREBP-2 axis was found to control germinal center B cell fate: 25-HC restrains SREBP-2 in GC B cells, and ectopic SREBP-2 drives rapid plasma cell differentiation, establishing SREBP-2 as a metabolic rheostat for humoral immunity.

    Evidence Ch25h−/− mice, B cell-specific SREBP-2 overexpression/deficiency, plasma cell assays, Salmonella infection model

    PMID:34644558

    Open questions at the time
    • Downstream cholesterol-dependent effectors mediating plasma cell commitment not identified
    • Whether dietary cholesterol modulates this axis in humans unknown
  19. 2021 Medium

    SREBP-2 was shown to directly bind and transactivate mesenchymal gene promoters (snai1, αSMA, vimentin, N-cadherin) in endothelial cells, driving endothelial-to-mesenchymal transition relevant to pulmonary fibrosis.

    Evidence Transcriptome analysis, ChIP for SREBP-2 at mesenchymal gene promoters, EC-SREBP2(N) transgenic mice with bleomycin model, human IPF specimens

    PMID:34806652

    Open questions at the time
    • Whether mesenchymal gene transactivation requires SRE elements or alternative motifs not defined
    • Single-lab finding
  20. 2022 Medium

    Multiple upstream regulators of SREBP-2 processing and stability were elaborated: ER Ca2+ was identified as a master brake on SREBP-2 activation; NF-κB–STARD10 signaling controls accessible cholesterol to trigger SCAP-SREBP-2 processing in endothelial cells; unspliced XBP1 stabilizes SREBP-2 by inhibiting its ubiquitination; KIF11 physically interacts with SREBP-2 to attenuate its degradation; and caspase-3 mediates an alternative SREBP-2 cleavage in HCC.

    Evidence ER Ca2+ manipulation with caffeine/analogs and human cohort; NF-κB inhibition and STARD10 genetic screen in ECs; XBP1-u co-localization and ubiquitination assays; KIF11 Co-IP and ubiquitination assay in PDAC; CASP3-SREBP-2 cleavage assay in drug-resistant HCC xenografts

    PMID:35140212 PMID:35619540 PMID:35767704 PMID:35933495 PMID:35959888

    Open questions at the time
    • ER Ca2+ sensor linking calcium to SREBP-2 processing not identified
    • STARD10's cholesterol transfer mechanism and specificity not defined
    • XBP1-u stabilization mechanism lacks structural detail
    • KIF11-SREBP-2 interaction domain not mapped
    • CASP3 cleavage site on SREBP-2 not identified
  21. 2022 Medium

    SREBP-2's non-canonical transcriptional targets were further expanded to include NLRC4 in keratinocytes (linking cholesterol signaling to inflammasome activation in psoriasis), YAP effector genes in endothelial cells (linking uric acid to endothelial dysfunction), and Zika virus co-opted lipid genes in dendritic cells.

    Evidence ChIP for SREBP-2 at NLRC4 promoter plus imiquimod mouse model; SREBP-2 siRNA epistasis on YAP activity in ECs plus hyperuricemia mouse; ChIP and SREBP-2 inhibition in ZIKV-infected DCs

    PMID:33977576 PMID:35120997 PMID:36097162

    Open questions at the time
    • Generalizability of NLRC4 regulation beyond keratinocytes untested
    • Mechanism by which SREBP-2 activates YAP target genes (direct binding vs. indirect) incompletely resolved
    • Host-virus specificity of SREBP-2 exploitation unknown
  22. 2023 High

    SREBP-2 protein was shown to be stabilized by deubiquitination: USP28 directly binds mature SREBP-2 and removes ubiquitin chains, increasing mevalonate pathway output—and USP28 loss sensitizes squamous cancer cells to statins, establishing a druggable vulnerability.

    Evidence Co-immunoprecipitation, in vitro deubiquitination assay, USP28 KO, CRISPR SREBP-2 deletion in mouse cancer model, metabolic flux

    PMID:37202505

    Open questions at the time
    • Ubiquitin chain type removed by USP28 not specified
    • Whether USP28 counteracts ITCH specifically on SREBP-2 not tested
  23. 2023 High

    PKCλ/ι was identified as a negative regulator of SREBP-2 by phosphorylating SCAP to promote its degradation; loss of PKCλ/ι unleashes SREBP-2-driven cholesterol biosynthesis that drives serrated colorectal cancer, connecting atypical PKC signaling to tumor-promoting SREBP-2 activation.

    Evidence Intestinal epithelial PKCλ/ι conditional KO, SCAP phosphorylation/degradation assays, SREBP-2 processing, mouse tumor model, human tissue

    PMID:38092754

    Open questions at the time
    • Specific SCAP phosphorylation sites targeted by PKCλ/ι not fully mapped
    • Whether other aPKC isoforms compensate not addressed
  24. 2024 High

    SREBP-2 was shown to act as a metabolic reprogramming switch in tumor-associated dendritic cells: melanoma-derived lactate activates SREBP-2, transforming DCs into immunosuppressive mregDCs that dampen CD8+ T cell responses, and DC-specific SREBP-2 silencing restores antitumor immunity.

    Evidence Transcriptional/metabolic profiling, DC-specific genetic silencing, pharmacologic SREBP-2 inhibition, CD8+ T cell assays, preclinical melanoma models, human sentinel lymph node analysis

    PMID:38728412

    Open questions at the time
    • Specific SREBP-2 target genes mediating mregDC transformation not defined
    • Whether other tumor-derived metabolites converge on SREBP-2 in DCs unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the kinase(s) opposing PP2A on nuclear SREBP-2, the structural basis for how diverse post-translational modifications (ubiquitination, phosphorylation, deubiquitination) coordinately tune SREBP-2 stability and DNA binding, and whether the expanding non-canonical target repertoire reflects bona fide SRE-dependent transcription or context-specific chromatin remodeling.
  • No structural model of SREBP-2 N-terminal domain bound to SRE-1 exists
  • Systematic mapping of SREBP-2 phosphorylation sites and their functional significance is lacking
  • Genome-wide ChIP-seq defining the complete SREBP-2 cistrome across tissues has not been integrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 12 GO:0003677 DNA binding 7
Localization
GO:0005634 nucleus 4 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-1430728 Metabolism 11 R-HSA-74160 Gene expression (Transcription) 7 R-HSA-392499 Metabolism of proteins 4 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 2
Partners
ATF6HDAC1ITCHKIF11PP2AQKISCAPUSP28
Complex memberships
ATF6-SREBP-2-HDAC1 repressive complexQki-SREBP-2 co-activator complexSCAP-SREBP-2 ER transport complex

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 SREBP-2 is a bHLH-Zip transcription factor that binds sterol regulatory element 1 (SRE-1) and activates transcription of genes controlling cholesterol synthesis and uptake; it contains an acidic NH2-terminal transactivation domain, a conserved bHLH-Zip motif, and a long COOH-terminal regulatory domain. In vitro DNA binding and in vivo reporter assays demonstrated SRE-1 binding specificity and transcriptional activation capacity. cDNA cloning, in vitro DNA binding assay, cotransfection reporter assay in HEK293 cells Proceedings of the National Academy of Sciences of the United States of America High 7903453
1996 SREBP-2 is released from the endoplasmic reticulum membrane by two sequential proteolytic cleavages: the first, sterol-regulated, occurs in the lumenal loop between the two transmembrane segments; the second, sterol-independent, occurs within the first transmembrane domain. The liberated NH2-terminal transcription factor domain then enters the nucleus to activate cholesterol biosynthesis and uptake genes. H-Ras-SREBP-2 fusion protein expression, mutant CHO cell analysis, cell fractionation, transcriptional reporter assays Cell High 8674110
1997 The SREBF2 gene spans 72 kb and is composed of 19 exons and 18 introns; a perfect 10-bp SRE-1 sequence is present in the SREBF2 promoter, providing a mechanism for autoregulation of its own transcription by sterol levels. Genomic cloning, sequencing, 5'-flanking region analysis, transcription start site mapping Genomics High 9070916
2004 ATF6 N-terminal fragment (ATF6(N)) directly binds to SREBP-2 N-terminal fragment (SREBP2(N)) through its leucine-zipper domain; the ATF6-SREBP-2 complex recruits HDAC1 to SRE-bound SREBP-2, attenuating SREBP-2 transcriptional activity and suppressing lipogenesis in liver cells. GST pull-down, co-immunoprecipitation, deletion mutagenesis, chromatin immunoprecipitation (ChIP), reporter assay The EMBO journal High 14765107
2003 SREBP-2 directly activates transcription of the IDH1 (cytosolic NADP-dependent isocitrate dehydrogenase) gene by binding to a specific SRE sequence (GTGGGCTGAG) in the IDH1 promoter, linking cholesterol/fatty acid biosynthetic regulation to NADPH generation. Promoter-reporter assays, electrophoretic mobility shift assay (EMSA), mutagenesis, sterol-depletion experiments Journal of lipid research High 12923220
2010 The primary transcript of SREBF2 contains an intronic miRNA (miR-33a) that reduces cellular cholesterol export by inhibiting translation of ABCA1, and also inhibits fatty acid β-oxidation by suppressing CPT1A, HADHB, and CROT, functionally coupling cholesterol synthesis promotion with prevention of cholesterol export and lipid degradation. Identification of miRNA within SREBF2 intron, transfection-based translation inhibition assays, functional cholesterol export and FAO assays The Journal of biological chemistry High 20732877
2013 FoxO3 recruits Sirt6 to the Srebp2 gene promoter, where Sirt6 deacetylates histone H3 at lysines 9 and 56 to promote a repressive chromatin state, thereby reducing hepatic SREBP-2 expression and cholesterol biosynthesis. Hepatic Sirt6 deficiency elevates cholesterol levels, and Sirt6 or FoxO3 overexpression improves hypercholesterolemia in obese mice. Hepatic Sirt6 knockout mice, chromatin immunoprecipitation, overexpression in vivo, cholesterol measurement Journal of lipid research High 23881913
2015 SREBP-2 directly binds to an SREBP-2-binding element in the 5'-flanking c-Myc promoter region and drives c-Myc transcriptional activation, inducing cancer stem cell-like properties and metastasis in prostate cancer cells. Chromatin immunoprecipitation, promoter reporter assay, SREBP-2 overexpression/knockdown with functional assays (proliferation, invasion, prostasphere, xenograft) Oncotarget Medium 26883200
2016 SREBP-2 directly induces transcription of the long-chain acyl-CoA synthetase 1 (ACSL1) C-transcript via a specific SRE motif in the ACSL1 C-promoter; knockdown of endogenous SREBP-2 in HepG2 cells reduces ACSL1 expression, linking cholesterol-sensing SREBP-2 to fatty acid activation. Promoter activity assay, DNA binding assay (EMSA), SREBP-2 knockdown, statin treatment in hamsters and mice The Journal of biological chemistry High 26728456
2009 SREBP-1 and SREBP-2 directly bind the proximal promoter region of the CASP7 gene (encoding caspase 7) as demonstrated by chromatin immunoprecipitation, and knockdown of SREBP-1/2 strongly reduces caspase 7 mRNA and protein expression, identifying CASP7 as a direct SREBP target. ChIP, siRNA knockdown, quantitative PCR, Western blot The Biochemical journal Medium 19323650
2010 SREBP-2 directly regulates NPC1L1 promoter activity in a dose-dependent manner and binds to the NPC1L1 promoter in vivo; overexpression of active SREBP-2 protects NPC1L1 from inhibitory effects, establishing NPC1L1 as a direct SREBP-2 target gene in human liver. Luciferase promoter assay, ChIP, SREBP-2 overexpression, correlation analysis in human liver biopsies Journal of lipid research High 20460578
2011 Curcumin reduces SREBP-2 DNA-binding activity and nuclear translocation partly through AMPK activation, thereby suppressing NPC1L1 promoter activity and cholesterol absorption; overexpression of active SREBP-2 rescues NPC1L1 from curcumin inhibition, demonstrating SREBP-2 mediates NPC1L1 regulation. Reporter assay, Western blot, AMPK activation measurement, SREBP-2 overexpression rescue, EMSA American journal of physiology. Gastrointestinal and liver physiology Medium 21527728
2012 Oligomeric Aβ42 inhibits SREBP-2 proteolytic cleavage in neurons, causing decreased protein prenylation and cholesterol sequestration; supplying geranylgeranyl pyrophosphate to Aβ-treated neurons restores prenylation, reduces cholesterol sequestration, and prevents neurotoxicity, identifying SREBP-2 as a target of Aβ neurotoxicity. Intracellular Aβ42 delivery, SREBP-2 cleavage assay (Western blot), prenylation assays, isoprenoid supplementation rescue, cortex analysis in TgCRND8 mice The Journal of neuroscience Medium 22573671
2013 TLR4-MyD88-NF-κB signaling increases SCAP expression and promotes abnormal SCAP translocation from the ER to the Golgi, activating the SCAP-SREBP-2 pathway to upregulate LDLR and HMG-CoAR expression and drive macrophage foam cell formation; MyD88 knockdown or IKK inhibition blocks these effects. siRNA knockdown, Western blot, RT-PCR, immunofluorescence/confocal microscopy, cholesterol measurement in THP-1 macrophages American journal of physiology. Heart and circulatory physiology Medium 23335792
2014 PP2A directly interacts with nuclear SREBP-2 in response to cholesterol depletion, alters its phosphorylation state, and promotes SREBP-2 DNA binding to the LDLR SRE promoter element, increasing LDLR expression and LDL uptake; PP2A inhibition or depletion by okadaic acid/siRNA abolishes SREBP-2 binding without affecting cleavage or nuclear translocation. Co-immunoprecipitation, siRNA knockdown, okadaic acid inhibition, ChIP/DNA binding assay, LDL uptake assay The Journal of biological chemistry High 24770487
2014 Hepatic insulin receptor is required for normal SREBP-2 activation in response to feeding and statin treatment; LIRKO mice lacking liver insulin receptors show suppressed SREBP-2 and cholesterologenic gene expression, and the response of SREBP-2 to both fasting/refeeding and statin treatment is abolished, while ezetimibe (cholesterol absorption inhibitor) can still induce SREBP-2 in LIRKO livers. Liver insulin receptor knockout mice (LIRKO), gene expression microarray, Western blot, statin/ezetimibe treatment Journal of lipid research High 24516236
2015 ERBB4 activation by neuregulin-1 induces SREBP-2 cleavage and the appearance of mature SREBP-2 through a PI3K- and mTORC1/2-dependent (but AKT- and mTORC1-independent) pathway, increasing expression of cholesterol biosynthesis and LDL uptake genes; pharmacological inhibition of S1P protease blocks NRG1-induced cholesterol gene expression. ERBB4-ICD expression, NRG1 ligand stimulation, PI3K/mTOR inhibitor treatment, S1P protease inhibitor, immunoblot of cleaved SREBP-2, gene expression assays Science signaling Medium 26535009
2015 FXR activation in mice induces SREBP-2 gene transcription (via an FXR response element in intron 10 of Srebp-2) and increases miR-33 levels, but simultaneously induces INSIG-2A, which prevents SCAP-mediated SREBP-2 processing, thereby uncoupling miR-33 and SREBP-2 target gene programs. ChIP-seq (FXR response element identification), FXR agonist treatment in mice, Scap-/- epistasis, Western blot for precursor and nuclear SREBP-2, miR-33 quantification Arteriosclerosis, thrombosis, and vascular biology High 25593129
2015 ITCH E3 ubiquitin ligase ubiquitinates SREBP-2, promoting its clearance; loss of ITCH reduces SREBP-2 ubiquitination and degradation, increasing nuclear SREBP-2 and LDLR expression, lowering circulating cholesterol. ITCH also ubiquitinates SIRT6 to promote its breakdown, reducing fatty acid oxidation. ApoE-/-ITCH-/- mouse model, bone marrow transplantation, ubiquitination assay, cholesterol measurement, gene expression analysis Scientific reports Medium 25777360
2015 SREBP-2 deficiency causes embryonic lethality in mice, with surviving null mice showing alopecia, attenuated growth, and reduced adipose tissue; hypomorphic mice with low SREBP-2 have reduced hepatic cholesterol and nearly abolished liver SREBF1c transcripts, demonstrating SREBP-2 is required for SREBF1c expression in liver and for embryonic development. SREBP-2 knockout and hypomorphic mouse generation, gene expression analysis, cholesterol measurement, histology Journal of lipid research High 26685326
2020 Ring finger protein 5 (RNF5), an ER-anchored E3 ubiquitin ligase, mediates Lys-29-linked polyubiquitination of SCAP at Lys-305 in cytosolic loop 2, enhancing the interaction between SCAP luminal loops 1 and 7 (a conformational change required for SCAP-SREBP-2 activation) and thereby activating SREBP-2 and cholesterol biosynthesis. siRNA knockdown, RNF5 overexpression, ubiquitination assay, K305R SCAP mutant in SCAP-deficient cells, co-immunoprecipitation, SREBP-2 target gene measurement The Journal of biological chemistry High 32054686
2020 SREBP2 directly induces transcription of the iron carrier Transferrin (TF) gene in circulating melanoma cells, reducing intracellular iron pools, reactive oxygen species, and lipid peroxidation, thereby suppressing ferroptosis and conferring drug resistance. Single-cell RNA-seq, knockdown of SREBP2/TF, ferroptosis induction assays, lipid peroxidation measurement, xenograft tumor formation Cancer discovery Medium 33203734
2021 25-hydroxycholesterol (25-HC) produced by follicular dendritic cells directly restrains SREBP-2 activation in germinal center B cells; ectopic SREBP-2 expression drives rapid plasma cell differentiation, while SREBP-2 deficiency reduces plasma cell output, establishing a 25-HC-SREBP2 axis that shapes intestinal IgA responses. Ch25h-/- mouse model, B cell-specific SREBP-2 overexpression/deficiency, plasma cell differentiation assays, immunization and Salmonella infection models Immunity High 34644558
2021 Quaking (Qki) functions as a transcriptional co-activator of SREBP-2 in eye lens and oligodendrocytes by recruiting SREBP-2 and RNA polymerase II to promoter regions of cholesterol biosynthesis genes; Qki-deficient lens-specific mice show reduced cholesterol and progressive cataracts rescued by topical sterol administration. Lens-specific Qki knockout mice, transcriptome analysis, ChIP (SREBP-2 and Pol II), cholesterol measurement, sterol rescue experiment, direct DNA-binding assay Nature communications High 34021134
2021 Qki-5 acts as a transcriptional co-activator of SREBP-2 in oligodendrocytes to control cholesterol biosynthesis gene transcription required for myelinogenesis; Qki depletion in neural stem cells or OPCs impairs cholesterol biosynthesis and myelin assembly without blocking oligodendrocyte differentiation. Conditional Qki knockout in neural stem cells and OPCs, cholesterol measurement, transcriptome analysis, myelination phenotype assessment eLife High 33942715
2022 Caspase-3 (CASP3) mediates cleavage of SREBP-2 from the ER to promote cholesterol biosynthesis, which drives cancer stem cell expansion and resistance to sorafenib/lenvatinib via activation of the sonic hedgehog signaling pathway in hepatocellular carcinoma. Drug-resistant patient-derived xenografts, RNA-seq, CASP3 cleavage of SREBP-2 (Western blot), SREBP-2 loss-of-function, simvastatin treatment Cancer research Medium 35767704
2022 Caffeine increases hepatic ER Ca2+ levels, which blocks SREBP-2 transcriptional activation (and thus PCSK9 expression), resulting in increased LDLR expression and LDL clearance; ER Ca2+ is identified as a master regulator of SREBP-2 activation upstream of its proteolytic processing. Hepatic cell treatment with caffeine/caffeine analogs, ER Ca2+ measurement, PCSK9/LDLR expression, human volunteer cohort, mechanistic Ca2+ manipulation Nature communications Medium 35140212
2022 NF-κB activation by pro-inflammatory cytokines in endothelial cells reduces accessible cholesterol, leading to heightened sterol sensing and downstream canonical SCAP-SREBP-2 cleavage/activation; NF-κB induces STARD10, which mediates accessible cholesterol homeostasis in ECs and links inflammation to SREBP-2 activation. Primary human endothelial cell treatment with cytokines, SREBP-2 cleavage assay, NF-κB inhibition, SCAP dependence assay, STARD10 identification by genetic screening eLife Medium 35959888
2022 Unspliced XBP1 (XBP1-u) colocalizes with SREBP-2, inhibits SREBP-2 ubiquitination/proteasomal degradation, and stabilizes SREBP-2 protein to activate HMGCR transcription and cholesterol biosynthesis in hepatocellular carcinoma cells. Co-localization assay, ubiquitination assay, XBP1-u overexpression/knockdown, HMGCR expression measurement, cholesterol assay, xenograft Cellular and molecular life sciences Medium 35933495
2023 USP28, a deubiquitinating enzyme, directly binds mature SREBP-2 and deubiquitinates it, leading to SREBP-2 stabilization and increased mevalonate pathway enzyme expression; USP28 silencing reduces SREBP-2 protein levels and sensitizes squamous cancer cells to statins. Co-immunoprecipitation, deubiquitination assay, USP28 knockdown/knockout, metabolic flux analysis, tissue microarray, CRISPR/Cas9 SREBP-2 deletion in mouse cancer model Cell death and differentiation High 37202505
2020 NBEAL1 interacts with SCAP and PAQR3 at the Golgi and regulates SREBP-2 processing and LDLR expression; loss of NBEAL1 in arteries (associated with coronary artery disease risk variants) downregulates LDLR by impairing this SCAP-SREBP-2 regulatory complex. Co-immunoprecipitation (NBEAL1-SCAP-PAQR3), NBEAL1 knockdown, SREBP-2 processing assay, LDLR expression measurement, human genetic association Scientific reports Medium 32161285
2023 PKCλ/ι (atypical PKC) phosphorylates SCAP, promoting its degradation and inhibiting SREBP-2 processing and activation; loss of PKCλ/ι upregulates SREBP-2 and cholesterol biosynthesis, driving aggressive serrated colorectal cancer tumorigenesis. PKCλ/ι conditional knockout in intestinal epithelial cells, SCAP phosphorylation and degradation assays, SREBP-2 processing measurement, tumor model in mice and human tissue analysis Nature communications High 38092754
2024 Melanoma-derived lactate activates SREBP-2 in tumor-associated dendritic cells, driving their transformation into mature regulatory DCs (mregDCs) that suppress antitumor CD8+ T cell responses; DC-specific genetic silencing or pharmacologic inhibition of SREBP-2 restores antitumor immunity and suppresses melanoma progression. Transcriptional and metabolic profiling, DC-specific SREBP-2 genetic silencing, pharmacologic SREBP-2 inhibition, CD8+ T cell functional assays, preclinical melanoma models, human sentinel lymph node analysis Science immunology High 38728412
2022 SREBP-2 directly binds the promoter region of NLRC4 in keratinocytes and transactivates it in response to LCN2/24p3R signaling, linking cholesterol biosynthetic signaling to NLRC4 inflammasome activation and psoriatic inflammation. ChIP demonstrating SREBP-2 binding to NLRC4 promoter, SREBP-2 siRNA knockdown in keratinocytes, imiquimod-induced mouse model with SREBP-2 suppression The Journal of investigative dermatology Medium 35120997
2021 SREBP-2 directly binds promoter regions of mesenchymal genes (snai1, α-smooth muscle actin, vimentin, N-cadherin) and transactivates them in endothelial cells, inducing an endothelial-to-mesenchymal transition phenotype associated with pulmonary fibrosis; endothelial-specific SREBP-2 transgenic mice show exacerbated bleomycin-induced pulmonary fibrosis. Transcriptome analysis (SREBP-2 overexpression), ChIP (SREBP-2 binding to mesenchymal gene promoters), EC-SREBP2(N)-Tg mouse + bleomycin model, human IPF lung specimens JCI insight Medium 34806652
2022 HMGB1 regulates LDL transcytosis in endothelial cells through SREBP-2: loss of nuclear HMGB1 reduces SREBP-2 protein half-life and decreases SR-BI expression; conversely, LDL induces HMGB1 nuclear translocation in an SR-BI-dependent manner, creating a positive feedback loop. The effect requires SREBP-2 and SR-BI but not extracellular HMGB1 or RAGE. siRNA knockdown (HMGB1, SR-BI, SREBP-2), SREBP-2 protein stability assay, total internal reflection fluorescence microscopy of LDL transcytosis, HMGB1 nuclear localization imaging, endothelial HMGB1 KO mouse aortic LDL accumulation assay Arteriosclerosis, thrombosis, and vascular biology High 33054399
2022 SREBP-2-activated transcription of lipid metabolism genes promotes Zika virus (ZIKV) infection of dendritic cells; ZIKV infection increases SREBP recruitment to lipid gene promoters, and pharmacologic inhibition or genetic silencing of SREBP-2 suppresses ZIKV infection. Genomics profiling of ZIKV-infected vs. uninfected DCs, ChIP (SREBP recruitment), pharmacologic/siRNA inhibition of SREBP-2, viral infection assay Nature communications Medium 36097162
2022 KIF11 interacts with SREBP-2 protein and attenuates its ubiquitination-mediated degradation, stabilizing SREBP-2 and increasing mevalonate pathway enzyme expression to drive cholesterol synthesis and tumor progression in pancreatic ductal adenocarcinoma. Co-immunoprecipitation (KIF11-SREBP-2), ubiquitination assay, KIF11 overexpression/knockdown, SREBP-2-dependent rescue experiments, xenograft model Cancer medicine Medium 35619540
2021 SREBP-2 transactivates YAP target genes (including VCAM1, ICAM1, CYR61) in endothelial cells exposed to uric acid or monosodium urate; SREBP-2 knockdown by siRNA partially abolishes uric acid-induced YAP activity and pro-inflammatory gene expression, identifying SREBP2-YAP as a pathway driving gout-induced endothelial dysfunction. siRNA knockdown, adenovirus-SREBP2 overexpression, RNA sequencing, real-time PCR, endothelial transgenic mouse (SREBP2 OE), hyperuricemia mouse model, EndoPAT human assay FASEB journal Medium 33977576
2023 Disassociation of ERLIN2 from SCAP upon SNX10 deletion enhances SCAP-mediated SREBP-2 activation, increasing cholesterol biosynthesis and intestinal stem cell stemness, which promotes mucosal healing in colitis models. Conditional SNX10 KO in intestinal epithelial cells/ISCs, ERLIN2-SCAP co-immunoprecipitation, SREBP-2 activation assay, cholesterol measurement, organoid and mouse colitis models Science advances Medium 37647408

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element. Proceedings of the National Academy of Sciences of the United States of America 544 7903453
1996 Sterol-regulated release of SREBP-2 from cell membranes requires two sequential cleavages, one within a transmembrane segment. Cell 462 8674110
2010 Expression of miR-33 from an SREBP2 intron inhibits cholesterol export and fatty acid oxidation. The Journal of biological chemistry 303 20732877
2009 Enhanced free cholesterol, SREBP-2 and StAR expression in human NASH. Journal of hepatology 291 19231010
2020 The Lipogenic Regulator SREBP2 Induces Transferrin in Circulating Melanoma Cells and Suppresses Ferroptosis. Cancer discovery 195 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 171 27001618
2013 Hepatic SREBP-2 and cholesterol biosynthesis are regulated by FoxO3 and Sirt6. Journal of lipid research 148 23881913
2007 ABCG1 and ABCG4 are coexpressed in neurons and astrocytes of the CNS and regulate cholesterol homeostasis through SREBP-2. Journal of lipid research 131 17916878
2016 Irisin Inhibits Hepatic Cholesterol Synthesis via AMPK-SREBP2 Signaling. EBioMedicine 113 27211556
2020 COVID-19-activated SREBP2 disturbs cholesterol biosynthesis and leads to cytokine storm. Signal transduction and targeted therapy 110 32883951
2016 SREBP-2 promotes stem cell-like properties and metastasis by transcriptional activation of c-Myc in prostate cancer. Oncotarget 93 26883200
2022 Caspase-3-Induced Activation of SREBP2 Drives Drug Resistance via Promotion of Cholesterol Biosynthesis in Hepatocellular Carcinoma. Cancer research 92 35767704
1997 Structure of the human gene encoding sterol regulatory element binding protein 2 (SREBF2). Genomics 91 9070916
2024 A lactate-SREBP2 signaling axis drives tolerogenic dendritic cell maturation and promotes cancer progression. Science immunology 86 38728412
2022 Caffeine blocks SREBP2-induced hepatic PCSK9 expression to enhance LDLR-mediated cholesterol clearance. Nature communications 78 35140212
2003 IDH1 gene transcription is sterol regulated and activated by SREBP-1a and SREBP-2 in human hepatoma HepG2 cells: evidence that IDH1 may regulate lipogenesis in hepatic cells. Journal of lipid research 77 12923220
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 73 36534812
2011 Regulation of lipid homeostasis by the bifunctional SREBF2-miR33a locus. Cell metabolism 68 21356514
2015 SREBP-2-deficient and hypomorphic mice reveal roles for SREBP-2 in embryonic development and SREBP-1c expression. Journal of lipid research 58 26685326
2021 The cholesterol metabolite 25-hydroxycholesterol restrains the transcriptional regulator SREBP2 and limits intestinal IgA plasma cell differentiation. Immunity 55 34644558
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
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
2018 Metformin treatment prevents SREBP2-mediated cholesterol uptake and improves lipid homeostasis during oxidative stress-induced atherosclerosis. Free radical biology & medicine 50 29499335
2024 A single-nucleus transcriptomic atlas of primate liver aging uncovers the pro-senescence role of SREBP2 in hepatocytes. Protein & cell 46 37378670
2021 Activation of pregnane X receptor induces atherogenic lipids and PCSK9 by a SREBP2-mediated mechanism. British journal of pharmacology 46 33687065
2022 Matrine suppresses NLRP3 inflammasome activation via regulating PTPN2/JNK/SREBP2 pathway in sepsis. Phytomedicine : international journal of phytotherapy and phytopharmacology 45 36610161
2020 Dual targeting of SREBP2 and ERRα by carnosic acid suppresses RANKL-mediated osteoclastogenesis and prevents ovariectomy-induced bone loss. Cell death and differentiation 45 31907393
2010 HNF1alpha and SREBP2 are important regulators of NPC1L1 in human liver. Journal of lipid research 44 20460578
2015 ITCH modulates SIRT6 and SREBP2 to influence lipid metabolism and atherosclerosis in ApoE null mice. Scientific reports 42 25777360
2021 Role of endothelial cells in pulmonary fibrosis via SREBP2 activation. JCI insight 41 34806652
2020 Endothelial HMGB1 Is a Critical Regulator of LDL Transcytosis via an SREBP2-SR-BI Axis. Arteriosclerosis, thrombosis, and vascular biology 38 33054399
2021 Qki activates Srebp2-mediated cholesterol biosynthesis for maintenance of eye lens transparency. Nature communications 37 34021134
2019 Industrial Trans Fatty Acids Stimulate SREBP2-Mediated Cholesterogenesis and Promote Non-Alcoholic Fatty Liver Disease. Molecular nutrition & food research 36 31327168
2019 LncRNA SNHG16 induces the SREBP2 to promote lipogenesis and enhance the progression of pancreatic cancer. Future oncology (London, England) 36 31664866
2011 SREBP2 mediates the modulation of intestinal NPC1L1 expression by curcumin. American journal of physiology. Gastrointestinal and liver physiology 36 21527728
2016 SREBP2 Activation Induces Hepatic Long-chain Acyl-CoA Synthetase 1 (ACSL1) Expression in Vivo and in Vitro through a Sterol Regulatory Element (SRE) Motif of the ACSL1 C-promoter. The Journal of biological chemistry 35 26728456
2015 Neuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake. Science signaling 35 26535009
2012 β-amyloid inhibits protein prenylation and induces cholesterol sequestration by impairing SREBP-2 cleavage. The Journal of neuroscience : the official journal of the Society for Neuroscience 35 22573671
2022 Inflammatory stress signaling via NF-kB alters accessible cholesterol to upregulate SREBP2 transcriptional activity in endothelial cells. eLife 34 35959888
2022 SREBP2-dependent lipid gene transcription enhances the infection of human dendritic cells by Zika virus. Nature communications 34 36097162
2014 Hepatic insulin receptor deficiency impairs the SREBP-2 response to feeding and statins. Journal of lipid research 34 24516236
2009 Human caspase 7 is positively controlled by SREBP-1 and SREBP-2. The Biochemical journal 34 19323650
2008 Coordinate induction of PPAR alpha and SREBP2 in multifunctional protein 2 deficient mice. Biochimica et biophysica acta 34 18773970
2021 Berberine mitigates nonalcoholic hepatic steatosis by downregulating SIRT1-FoxO1-SREBP2 pathway for cholesterol synthesis. Journal of integrative medicine 33 34686466
2022 LCN2 Mediates Skin Inflammation in Psoriasis through the SREBP2‒NLRC4 Axis. The Journal of investigative dermatology 32 35120997
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 30 37859702
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
2018 Diabetes Mellitus in Pregnancy Leads to Growth Restriction and Epigenetic Modification of the Srebf2 Gene in Rat Fetuses. Hypertension (Dallas, Tex. : 1979) 30 29610268
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 Nutrient deprivation induces α-synuclein aggregation through endoplasmic reticulum stress response and SREBP2 pathway. Frontiers in aging neuroscience 29 25339898
2024 Cholesterol homeostasis confers glioma malignancy triggered by hnRNPA2B1-dependent regulation of SREBP2 and LDLR. Neuro-oncology 28 38070488
2022 Hydroxylation site-specific and production-dependent effects of endogenous oxysterols on cholesterol homeostasis: Implications for SREBP-2 and LXR. The Journal of biological chemistry 28 36423680
2015 Anti-Inflammatory Effects of Ang-(1-7) in Ameliorating HFD-Induced Renal Injury through LDLr-SREBP2-SCAP Pathway. PloS one 27 26291618
2023 USP28 controls SREBP2 and the mevalonate pathway to drive tumour growth in squamous cancer. Cell death and differentiation 26 37202505
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 26 32028704
2020 NBEAL1 controls SREBP2 processing and cholesterol metabolism and is a susceptibility locus for coronary artery disease. Scientific reports 26 32161285
2015 The nuclear receptor FXR uncouples the actions of miR-33 from SREBP-2. Arteriosclerosis, thrombosis, and vascular biology 26 25593129
2021 Qki regulates myelinogenesis through Srebp2-dependent cholesterol biosynthesis. eLife 25 33942715
2023 Loss of hepatic FTCD promotes lipid accumulation and hepatocarcinogenesis by upregulating PPARγ and SREBP2. JHEP reports : innovation in hepatology 24 37675273
2022 Increased LDL receptor by SREBP2 or SREBP2-induced lncRNA LDLR-AS promotes triglyceride accumulation in fish. iScience 23 35811843
2022 Butyrate Lowers Cellular Cholesterol through HDAC Inhibition and Impaired SREBP-2 Signalling. International journal of molecular sciences 23 36555149
1994 Sterol mediated regulation of SREBP-1a,1b,1c and SREBP-2 in cultured human cells. Biochemical and biophysical research communications 23 8060328
2023 Inhibiting sorting nexin 10 promotes mucosal healing through SREBP2-mediated stemness restoration of intestinal stem cells. Science advances 22 37647408
2023 Enhanced SREBP2-driven cholesterol biosynthesis by PKCλ/ι deficiency in intestinal epithelial cells promotes aggressive serrated tumorigenesis. Nature communications 22 38092754
2015 MicroRNA-185-5p mediates regulation of SREBP2 expression by hepatitis C virus core protein. World journal of gastroenterology 22 25914460
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 21 35037821
2022 KIF11 manipulates SREBP2-dependent mevalonate cross talk to promote tumor progression in pancreatic ductal adenocarcinoma. Cancer medicine 21 35619540
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
2011 Dysregulation of SREBP2 induces BACE1 expression. Neurobiology of disease 21 21726644
2024 ALOX15B controls macrophage cholesterol homeostasis via lipid peroxidation, ERK1/2 and SREBP2. Redox biology 20 38581859
2023 ABCA9, an ER cholesterol transporter, inhibits breast cancer cell proliferation via SREBP-2 signaling. Cancer science 20 36576228
2020 NPY stimulates cholesterol synthesis acutely by activating the SREBP2-HMGCR pathway through the Y1 and Y5 receptors in murine hepatocytes. Life sciences 20 32976883
2024 LINC00618 facilitates growth and metastasis of hepatocellular carcinoma via elevating cholesterol synthesis by promoting NSUN2-mediated SREBP2 m5C modification. Ecotoxicology and environmental safety 19 39299205
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
2022 Exosomal miR-673-5p from fibroblasts promotes Schwann cell-mediated peripheral neuron myelination by targeting the TSC2/mTORC1/SREBP2 axis. The Journal of biological chemistry 18 35151688
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
2021 Identification of neolignans with PCSK9 downregulatory and LDLR upregulatory activities from Penthorum chinense and the potential in cholesterol uptake by transcriptional regulation of LDLR via SREBP2. Journal of ethnopharmacology 18 34111537
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
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 16 38103317
2022 LncRNA NEAT1 Potentiates SREBP2 Activity to Promote Inflammatory Macrophage Activation and Limit Hantaan Virus Propagation. Frontiers in microbiology 16 35495674
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
2014 Protein phosphatase 2A (PP2A) regulates low density lipoprotein uptake through regulating sterol response element-binding protein-2 (SREBP-2) DNA binding. The Journal of biological chemistry 16 24770487
2024 Influenza A virus infection activates STAT3 to enhance SREBP2 expression, cholesterol biosynthesis, and virus replication. iScience 15 39108727
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
2024 Gypenoside L inhibits hepatocellular carcinoma by targeting the SREBP2-HMGCS1 axis and enhancing immune response. Bioorganic chemistry 14 38861912
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
2017 Cholesterol auxotrophy and intolerance to ezetimibe in mice with SREBP-2 deficiency in the intestine. Journal of lipid research 14 28630260
2023 SREBP2 inhibitor betulin sensitizes hepatocellular carcinoma to lenvatinib by inhibiting the mTOR/IL-1β pathway. Acta biochimica et biophysica Sinica 13 37434430
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
2021 The Cholesterol-Lowering Effect of Capsella Bursa-Pastoris Is Mediated via SREBP2 and HNF-1α-Regulated PCSK9 Inhibition in Obese Mice and HepG2 Cells. Foods (Basel, Switzerland) 13 33673187
2021 PRL-1 overexpressed placenta-derived mesenchymal stem cells suppress adipogenesis in Graves' ophthalmopathy through SREBP2/HMGCR pathway. Stem cell research & therapy 13 34051850
2020 Expression of SREBP2 and cholesterol metabolism related genes in TCGA glioma cohorts. Medicine 13 32195924