Affinage

SREBF1

Sterol regulatory element-binding protein 1 · UniProt P36956

Length
1147 aa
Mass
121.7 kDa
Annotated
2026-06-10
100 papers in source corpus 40 papers cited in narrative 40 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

SREBF1 encodes SREBP-1, a basic helix-loop-helix-zipper transcription factor and master regulator of de novo fatty acid and triglyceride synthesis (PMID:7759101, PMID:15123649). Synthesized as an ER membrane-bound precursor, it requires SCAP-dependent ER-to-Golgi transport followed by sequential S1P/S2P proteolysis to liberate the active nuclear bHLH-Zip domain; this processing step is the principal control point, governed by SCAP-Insig interactions that are released by ammonia binding to SCAP Asp-428 (PMID:35534729), by CD36-INSIG2 complex formation (PMID:34974159), and conversely retained when fasting-induced PPARα drives Insig2a (PMID:28855656). Maturation is also gated by accessory factors that act on the trafficking machinery: CRTC2 blocks COPII-dependent transport until mTOR phosphorylates it (PMID:26147081), PAS kinase is required for processing (PMID:25001282), and FMO2 competitively binds SREBP1 (residues 217–296) to exclude SCAP (PMID:37874228). Insulin is the dominant physiological input, raising both SREBP-1c transcription—through a pre-formed LXRα–C/EBPβ complex on the promoter (PMID:27382175) and mTORC1 signaling—and proteolytic processing via an mTORC1→p70 S6-kinase arm (PMID:22927400); the human SREBF1 gene generates SREBP-1a and SREBP-1c isoforms by alternative splicing, with SREBP-1a's N-terminal extension conferring stronger coactivator (CBP/mediator) recruitment (PMID:7759101, PMID:15340088). The active factor is tuned post-translationally by acetylation (p300 at K289/K309 stabilizing, SIRT1 deacetylating and destabilizing) (PMID:20817729), inhibitory phosphorylation by SIK kinases at Ser-329 (PMID:19244231), PRMT5 methylation at R321 that blocks GSK3β-primed Fbw7 degradation (PMID:26759235), and competing ubiquitin pathways (TRIM21 promoting degradation; USP11 and E4BP4 promoting stability) (PMID:36694250, PMID:39558331, PMID:27252523). SREBP-1 is positioned within an LXR-coupled circuit linking cholesterol and fatty acid synthesis (PMID:28244871) and cooperates with ChREBP on distinct lipogenic and glycolytic gene sets (PMID:29335275), while it also activates glycolytic genes such as glucokinase and represses gluconeogenic PEPCK-C (PMID:15123649, PMID:14744869). Beyond lipogenesis, SREBP-1 contributes to macrophage inflammatory resolution and M2 activation (PMID:28041958, PMID:34531575), regulates autophagy/mitophagy and lipid-droplet turnover (PMID:37927089, PMID:34455909, PMID:24991824), coordinates NF-κB spatiotemporal activation through a Scap–SREBP1–S1P/S2P–IκBα supercomplex (PMID:37267109), and drives midbrain dopaminergic neurogenesis downstream of LXR (PMID:32375051).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1995 High

    Established the genomic structure of SREBF1 and the molecular basis for distinct SREBP-1 isoforms, defining the gene that encodes the lipogenic transcription factor.

    Evidence Gene cloning, sequencing, exon mapping, and cytogenetic localization to 17p11.2

    PMID:7759101

    Open questions at the time
    • Functional differences between splice isoforms not resolved at this stage
    • Regulatory mechanism of processing not yet addressed
  2. 1994 Medium

    Showed that SREBP-1 expression is itself sterol-regulated in an isoform-specific manner, indicating feedback control of the lipogenic program.

    Evidence RNase protection assay in HepG2 cells under cholesterol depletion

    PMID:8060328

    Open questions at the time
    • Single-method, single-lab measurement
    • Does not address proteolytic processing or transcriptional targets
  3. 2004 High

    Defined SREBP-1's direct transcriptional targets and dual gene-regulatory logic—activating glycolytic glucokinase while repressing gluconeogenic PEPCK-C—linking it to glucose as well as lipid metabolism, and mapped the isoform-specific coactivator interactions underlying SREBP-1a's stronger activation.

    Evidence Reporter assays, EMSA, ChIP, dominant-negative SREBP-1c in hepatocytes, and domain mapping of CBP/mediator binding

    PMID:14744869 PMID:15123649 PMID:15340088

    Open questions at the time
    • In vivo significance of PEPCK-C repression not quantified
    • Coactivator binding mapped in vitro/transfection contexts
  4. 2010 High

    Identified the acetylation switch and the insulin-mTORC1-S6K signaling architecture controlling SREBP-1c, separating transcriptional from proteolytic activation.

    Evidence Mass spectrometry site mapping, mutagenesis, ChIP in HepG2/mouse liver; transgenic rat plus rapamycin/S6K inhibition

    PMID:20817729 PMID:22927400

    Open questions at the time
    • Branch point downstream of mTORC1 driving transcription (non-S6K) not identified
    • Cross-talk between acetylation and processing not integrated
  5. 2014 High

    Established kinase requirements for SREBP-1c processing (PASK) and identified an inhibitory phosphorylation event (SIK at Ser-329), revealing layered kinase control of activation and inactivation.

    Evidence Genetic and pharmacological PASK inhibition in vivo; in vitro kinase assay, mutagenesis, and adenoviral rescue for SIK

    PMID:19244231 PMID:25001282

    Open questions at the time
    • Direct substrate relationship of PASK to processing machinery unclear
    • Upstream activators of SIK in this context not defined
  6. 2015 High

    Identified CRTC2 as an mTOR-controlled gatekeeper of COPII-mediated ER-to-Golgi transport of SREBP1, connecting nutrient signaling to the trafficking step of activation.

    Evidence Reciprocal Co-IP, COPII transport assays, hepatic expression of mTOR-defective CRTC2 mutant in obese mice

    PMID:26147081

    Open questions at the time
    • Relative contribution versus SCAP-Insig control not quantified
    • Stoichiometry of CRTC2/Sec23A/Sec31A competition undefined
  7. 2016 High

    Resolved how upstream signals stabilize SREBP-1 protein and induce its transcription—PRMT5 methylation blocking degradation, E4BP4 preserving acetylation, and a pre-formed LXRα–C/EBPβ promoter complex relaying insulin—broadening the regulatory network.

    Evidence Mass spectrometry, in vitro methylation and ubiquitination assays, Co-IP, ChIP, and in vivo siRNA knockdown

    PMID:26759235 PMID:27252523 PMID:27382175

    Open questions at the time
    • Interplay between PRMT5 methylation and acetylation marks not jointly tested
    • Whether E4BP4 acts on all isoforms unknown
  8. 2017 High

    Placed SREBP-1c within an LXR-coupled circuit that integrates cholesterol synthesis and fatty acid synthesis, and defined PPARα→Insig2a as the fasting brake on processing.

    Evidence Hepatocyte-specific Srebf-2 KO epistasis; PPARα-null mice with ChIP-mapped PPRE on Insig2a

    PMID:28244871 PMID:28855656

    Open questions at the time
    • Identity of the endogenous SREBP-2-derived LXR ligand not chemically defined
    • Tissue specificity of the PPARα-Insig2a brake not broadly tested
  9. 2018 High

    Demonstrated combinatorial control of SREBF1 by tissue-relevant factors—ChREBP cooperation on distinct gene sets and AR/nuclear mTOR co-regulation in cancer—showing SREBP-1's outputs are context-partitioned.

    Evidence ChREBP KO with AAV nuclear SREBP-1c rescue and Scap double-KO controls; ChIP for AR/mTOR at SREBF1 with pharmacological dissection

    PMID:29335275 PMID:29784665

    Open questions at the time
    • Mechanism partitioning lipogenic vs glycolytic genes between SREBP-1c and ChREBP unresolved
    • AR/mTOR study confined to a single cancer model
  10. 2021 High

    Extended SREBP-1 function beyond lipogenesis into immune, autophagy, and trafficking control, including macrophage M2 activation via NADPH/ROS, lipophagy regulation through the miR-216a/CTH/H2S/ULK1 axis, NPC2-mediated lipid mobilization, and CD36-INSIG2-driven processing.

    Evidence Genetic loss-of-function in macrophages with infection model and NADPH/ROS measurement; ULK1 point-mutant and CTH-silencing epistasis; autophagy flux assays; CD36 KO mice with PLA and pharmacological rescue

    PMID:34455909 PMID:34531575 PMID:34974159 PMID:37927089

    Open questions at the time
    • Whether non-lipogenic roles require canonical processing in each context not always tested
    • Some tumor/autophagy mechanisms characterized in single labs
  11. 2022 Medium

    Revealed metabolite- and stress-driven activation routes (ammonia binding SCAP, ER-stress/Akt in fibrosis) and a BRD2-dependent feedforward transcription circuit, expanding the input space of SREBP-1 activation.

    Evidence SCAP D428A mutagenesis with Co-IP and xenograft; ChIP at TGF-β promoter with ER-stress/S1P inhibition in angiotensin II model; ChIP-qPCR/EMSA/Co-IP of BRD2

    PMID:25398788 PMID:35534729 PMID:35694209

    Open questions at the time
    • Physiological range of ammonia-driven activation in normal tissue unclear
    • Fibrosis and BRD2 circuits each from single labs
  12. 2023 Medium

    Defined competing ubiquitin/deubiquitinase control (TRIM21 vs USP11), an enzymatically independent competitive inhibitor of processing (FMO2), m6A-based transcript stabilization (FTO), and a structural role in spatiotemporal NF-κB activation via the Scap–SREBP1–S1P/S2P–IκBα supercomplex.

    Evidence Co-IP/ubiquitination assays with domain mapping and tumor models; FMO2 KO/overexpression with SCAP competition; m6A and mRNA stability assays; supercomplex Co-IP with Scap KO and S1P/S2P inhibition

    PMID:36352530 PMID:36694250 PMID:37267109 PMID:37874228 PMID:39558331

    Open questions at the time
    • Ubiquitin and DUB studies confined to specific cancer contexts
    • Stoichiometry/regulation of the NF-κB supercomplex not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many parallel activating and inhibitory inputs (trafficking gatekeepers, metabolite sensors, post-translational marks, ubiquitin balance) are quantitatively integrated to set SREBP-1 activity in a given cell state remains unresolved.
  • No unified quantitative model integrating processing-stage and stability-stage controls
  • Isoform-specific deployment of these regulators across tissues not systematically mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 4
Localization
GO:0005783 endoplasmic reticulum 5 GO:0005634 nucleus 4 GO:0005794 Golgi apparatus 2
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-168256 Immune System 3 R-HSA-9612973 Autophagy 3
Partners
CD36CRTC2FMO2INSIG2PRMT5SCAPTRIM21USP11
Complex memberships
LXRα-C/EBPβ promoter complexScap-SREBP1-S1P/S2P-IκBα supercomplex

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 The human SREBF1 gene is 26 kb in length with 22 exons and 20 introns; alternative splicing at both 5' and 3' ends generates multiple SREBP-1 isoforms (including SREBP-1a and SREBP-1c), and the gene maps to chromosome 17p11.2. Gene cloning, sequencing, exon mapping, analysis of human-rodent somatic cell hybrids, fluorescence in situ hybridization Genomics High 7759101
1994 SREBP-1c and SREBP-2 mRNA levels increase under cholesterol depletion in HepG2 cells, while SREBP-1a/1b mRNA increases transiently then decreases, demonstrating isoform-specific sterol-mediated regulation of SREBP expression. RNase protection assay in cultured human hepatoma cells under cholesterol depletion and ALLN treatment Biochemical and biophysical research communications Medium 8060328
2010 SIRT1 directly deacetylates SREBP-1c, reducing its stability and occupancy at lipogenic gene promoters; p300 acetylates SREBP-1c at Lys-289 and Lys-309, and acetylation-defective mutants confirmed that acetylation enhances SREBP-1c transactivation and lipogenic gene expression. Co-immunoprecipitation, tandem mass spectrometry, site-directed mutagenesis, adenoviral siRNA knockdown, ChIP, acetylation assays in HepG2 cells and mouse liver The Journal of biological chemistry High 20817729
2010 Insulin activates SREBP-1c by two mechanisms: increasing SREBP-1c mRNA transcription and stimulating proteolytic processing (maturation) of the ER-bound precursor; both require mTORC1, but only processing requires p70 S6-kinase, indicating divergent downstream pathways after mTORC1. Transgenic rats expressing epitope-tagged human SREBP-1c in liver; pharmacological inhibition of mTORC1 (rapamycin) and S6K; isolated hepatocyte system Proceedings of the National Academy of Sciences of the United States of America High 22927400
2015 CRTC2 competes with COPII subunit Sec23A for binding to Sec31A, thereby blocking COPII-dependent ER-to-Golgi transport and proteolytic processing of SREBP1; mTOR phosphorylates CRTC2 to relieve this inhibition during feeding, promoting SREBP1 maturation and lipogenesis. Co-immunoprecipitation, hepatic overexpression of mTOR-defective CRTC2 mutant in obese mice, COPII transport assays Nature High 26147081
2004 SREBP-1a binds avidly to the coactivator CBP (via its C/H1 domain) and to the mediator complex (via DRIP150 aa 500–824), accounting for its stronger transcriptional activation compared to SREBP-1c, which lacks the 28 aa N-terminal extension required for these interactions. In vitro binding assays, co-immunoprecipitation, chromatin immunoprecipitation at SREBP-responsive promoters, deletion/domain-mapping analyses Molecular and cellular biology High 15340088
2016 PRMT5 binds SREBP1a and symmetrically dimethylates it at R321; this methylation prevents GSK3β-mediated phosphorylation at S430, blocking Fbw7/FBXW7-dependent ubiquitin-proteasome degradation and thereby stabilizing SREBP1a to promote de novo lipogenesis. Mass spectrometry identification of PRMT5 as binding partner, in vitro methylation assay, mutagenesis (R321 and S430), ubiquitination assays, in vivo tumor xenograft Cancer research High 26759235
2016 Insulin induction of SREBP-1c transcription in liver requires a LXRα–C/EBPβ complex that binds to the SREBP-1c promoter; insulin activates this pre-formed complex rather than inducing its formation, and C/EBPβ knockdown reduces insulin-stimulated SREBP-1c mRNA in hepatocytes and mice. Co-immunoprecipitation from rat liver nuclei, chromatin immunoprecipitation, adenoviral siRNA knockdown in primary rat hepatocytes and mouse liver Proceedings of the National Academy of Sciences of the United States of America High 27382175
2009 Salt-inducible kinase (SIK) family members phosphorylate nuclear SREBP-1c at Ser-329, inactivating it and reducing expression of lipogenic target genes; adenoviral SIK1 overexpression lowers hepatic triglycerides and this is rescued by co-expression of a SIK-unresponsive SREBP-1c mutant. In vitro kinase assay, site-directed mutagenesis, adenoviral overexpression and rescue experiments in primary hepatocytes and mouse liver The Journal of biological chemistry High 19244231
2017 Hepatocyte-specific deletion of Srebf-2 eliminates production of an endogenous sterol ligand required for LXR activity, which in turn markedly reduces SREBP-1c expression and all LXR-dependent fatty acid/triglyceride synthesis genes, demonstrating that cholesterol and fatty acid synthesis are coupled through LXR-mediated SREBP-1c transcription. Conditional hepatocyte-specific Srebf-2 knockout mice, gene expression analysis, genetic epistasis eLife High 28244871
2022 Ammonia (released from glutamine) binds to SCAP and promotes SCAP-Insig dissociation, triggering SREBP-1 translocation from ER to Golgi for processing and lipogenic gene activation; mutation of SCAP Asp-428 prevents ammonia binding and abolishes SREBP-1 activation, while 25-hydroxycholesterol blocks the ammonia binding site on SCAP. SCAP mutagenesis (D428A), SCAP-Insig co-immunoprecipitation, tumor xenograft in vivo, pharmacological competition with 25-hydroxycholesterol Nature metabolism High 35534729
2021 CD36 forms a complex with INSIG2, disrupting the SCAP-INSIG2 interaction and thereby allowing SREBP1 to translocate from ER to Golgi for proteolytic processing; insulin activates CD36 in this pathway, and 25-hydroxycholesterol or betulin (which enhance SCAP-INSIG interaction) reverse CD36-driven SREBP1 cleavage. Co-immunoprecipitation, proximity ligation assay, hepatocyte-specific CD36 knockout mice, CD36 overexpression in HepG2 cells, pharmacological rescue Molecular metabolism High 34974159
2014 PAS kinase (PASK) is required for proteolytic maturation of SREBP-1c (ER-precursor to nuclear form) in liver; genetic and pharmacological inhibition of PASK reduces SREBP-1c processing and lipogenic target gene expression in cultured cells and in mouse/rat liver in vivo. Genetic PASK knockout, pharmacological PASK inhibitors, in vivo mouse/rat liver assays for SREBP-1c processing Cell reports High 25001282
2016 SREBP1 (not LXR) drives the late anti-inflammatory fatty acid biosynthesis program 12–24 hr after TLR4 activation in macrophages, resulting in uncoupling of NFκB binding from gene activation and contributing to resolution of inflammatory responses. Loss-of-function (SREBP1 knockout/knockdown), gene expression profiling, LXR deletion controls, macrophage functional assays Cell metabolism High 28041958
2004 SREBP-1c binds to two sterol regulatory elements (SREa, SREb) in the rat glucokinase (LGK) promoter and activates its transcription; insulin selectively increases SREBP-1c binding to these sites in primary hepatocytes, and a dominant-negative SREBP-1c blocks insulin-induced LGK expression. Reporter assays, electrophoretic mobility shift assay, chromatin immunoprecipitation in primary hepatocytes, adenoviral dominant-negative SREBP-1c The Journal of biological chemistry High 15123649
2004 SREBP-1c (and SREBP-1a, SREBP-2) represses transcription of the PEPCK-C gene by binding to two SREs in its promoter; at the -590 SRE, SREBP-1c and Sp1 compete for binding on opposite strands, and a single T/A base change converts the PEPCK-C SRE from an inhibitory to an activating element. Reporter assays, EMSA with purified proteins, chromatin immunoprecipitation in rat hepatocytes, site-directed mutagenesis of promoter elements The Journal of biological chemistry High 14744869
2023 FTO demethylates m6A sites on SREBF1 mRNA, stabilizing the transcript and increasing SREBP1 protein and downstream lipogenic gene expression; insulin stimulates FTO transcription via intranuclear insulin receptor beta, and FTO knockdown abrogates the lipogenic effect of insulin. FTO overexpression/knockdown in hepatocytes and mice, m6A methylation assays, mRNA stability assays, SREBF1/ChREBP knockdown epistasis Journal of molecular cell biology Medium 36352530
2021 SREBF1 concurrently activates de novo lipid synthesis and macroautophagy (lipophagy) in tumor cells; it upregulates NPC2 (a lysosomal cholesterol transporter) to mobilize lipid-droplet-stored cholesterol and fatty acids, thereby maintaining lipid homeostasis for tumor growth. Loss-of-function studies, autophagy flux assays, lipid droplet quantification, gene expression analysis in tumor cells Autophagy Medium 37927089
2021 SREBF1 activation directly upregulates miR-216a transcription, which reduces CTH/CSE expression and H2S production; reduced H2S impairs ULK1 sulfhydration, inhibiting autophagy-mediated lipid droplet turnover (lipophagy) and promoting hepatic steatosis. High-fat diet mouse model, ULK1 C951S point mutant, CTH silencing, measurement of H2S production and autophagic flux Autophagy Medium 34455909
2021 SREBP1 is activated by IL-4 in macrophages, driving de novo lipogenesis (DNL) that consumes NADPH; reduced NADPH elevates reactive oxygen species (ROS), which act as second messengers to promote macrophage alternative (M2) activation. SREBP1 loss-of-function in macrophages, helminth infection model in vivo, ROS measurement, NADPH assays, IL-4 stimulation Nature metabolism High 34531575
2023 The lipogenesis cascade Scap–SREBP1–S1P/S2P forms a super complex with IκBα that sequesters NF-κB near the ER; upon LPS stimulation, Scap transports the complex to the Golgi where S1P/S2P cleaves SREBP1, liberating IκBα for phosphorylation and NF-κB activation. Co-immunoprecipitation of Scap/SREBP1/IκBα complex, Scap knockout, S1P/S2P inhibition, LPS stimulation assays, subcellular fractionation Cell reports High 37267109
2017 PPARα transcriptionally activates Insig2a expression via a PPAR-responsive element in its promoter during fasting; elevated Insig2a retains SCAP/SREBP-1c in the ER, thereby suppressing SREBP-1c proteolytic processing and lipogenesis during nutrient starvation. Transient transfection reporter assay, chromatin immunoprecipitation, Pparα-null mice, primary hepatocyte assays Scientific reports High 28855656
2018 The androgen receptor (AR) and nuclear mTOR co-bind regulatory regions of SREBF1 to control its transcription; dual AR/mTOR activation also promotes SREBF1 cleavage and nuclear translocation, and SREBF1 in turn recruits to FASN and SCD1 promoters to drive lipogenesis in prostate cancer cells. Chromatin immunoprecipitation, pharmacological inhibition of mTOR, genetic inhibition of SREBF1, nuclear fractionation, lipid accumulation assays Molecular cancer research Medium 29784665
2016 E4BP4, induced by insulin via AKT-mTORC1-SREBP-1c, interacts with nuclear SREBP-1c to preserve its acetylation and protect it from ubiquitination-dependent proteasomal degradation, thereby sustaining robust de novo lipogenesis during the fed state. Co-immunoprecipitation of E4BP4 and nuclear SREBP-1c, adenoviral shRNA knockdown of E4bp4 in mouse liver, ubiquitination assays, lipogenesis assays Journal of lipid research Medium 27252523
2014 SREBF1 is required for PINK1-PARK2-mediated mitophagy; RNAi screen in Drosophila and human cells identified lipogenesis pathway components including SREBF1 as conserved regulators of mitophagy, and results suggest lipids influence PINK1 stabilization during mitophagy initiation. Genome-wide RNAi screen in Drosophila and human cell models, functional mitophagy assays Autophagy Medium 24991824
2015 Srebp-1 physically interacts with c-Myc, facilitating c-Myc binding to downstream pluripotent gene targets and strengthening c-Myc-mediated enhancement of other Yamanaka factors' binding; this role in somatic cell reprogramming depends on Srebp-1 transcriptional activity but not its ability to bind the canonical E-box motif. Co-immunoprecipitation of Srebp-1 with c-Myc, overexpression and knockdown experiments, analysis of pluripotent gene expression during reprogramming Stem cells Medium 26388522
2020 Srebf1 is both required and sufficient for midbrain dopaminergic (mDA) neurogenesis; Srebf1 acts downstream of LXR activation, is expressed in radial glia proneural clusters, and regulates transcription factors controlling mDA neurogenesis including Foxa2. ChIP-seq and transcriptome analysis after LXR activation; loss-of-function and gain-of-function experiments in vitro and in vivo in mice Cell reports High 32375051
2021 Hepatic deletion of Mboat7 activates SREBP-1c processing, leading to increased de novo lipogenesis and fatty liver; genetic removal of Scap (which prevents all SREBP processing) in Mboat7-KO mice normalizes hepatic triglycerides, establishing that SREBP-1c processing is required for Mboat7-induced steatosis. Liver-specific Mboat7 KO mice, double KO (Mboat7/Scap), lipidomics, genetic epistasis Journal of lipid research High 32859645
2023 FMO2 directly binds SREBP1 at amino acids 217–296, competing with SCAP for binding to SREBP1 and thereby blocking ER-to-Golgi transport and subsequent proteolytic activation of SREBP1; this suppresses de novo lipogenesis independently of FMO2's enzymatic activity. Co-immunoprecipitation, RNA sequencing, hepatocyte-specific and global FMO2 knockout mice, FMO2 overexpression in mice, domain mapping Hepatology High 37874228
2023 TRIM21 ubiquitinates SREBF1, targeting it for proteasomal degradation; knockdown of TRIM21 increases SREBF1 protein and lipogenic enzyme expression, promoting lipid accumulation in renal carcinoma cells, and SREBF1 is critical for TRIM21-mediated lipogenesis inhibition in vivo. Co-immunoprecipitation, ubiquitination assays, TRIM21 knockdown and overexpression, orthotopic tumor model Journal of experimental & clinical cancer research Medium 36694250
2024 USP11 directly interacts with SREBF1 (via USP11 503–938 aa binding SREBF1 569–1147 aa at K1151) and stabilizes it through K48-linked deubiquitination, preventing proteasomal degradation; USP11 silencing leads to SREBF1 degradation and reduced lipogenesis and tumorigenesis in hepatocellular carcinoma. Mass spectrometry, co-immunoprecipitation, ubiquitination assays with domain mapping, xenograft mouse model Cell communication and signaling Medium 39558331
2022 SREBP-1 is activated by angiotensin II in mesangial cells via PI3K/Akt signaling, requiring SCAP and protease S1P; ER stress acts as a key mediator of Akt-SREBP-1 activation, and activated SREBP-1 binds the TGF-β promoter to upregulate TGF-β and fibronectin, driving glomerular fibrosis. ChIP of SREBP-1 at TGF-β promoter, pharmacological inhibition of ER stress and S1P, SREBP inhibitor fatostatin in vivo, angiotensin II infusion mouse model Journal of the American Society of Nephrology Medium 25398788
2012 SIRT1 regulates SREBP-1c expression in skeletal muscle in an LXR-dependent manner; SIRT1 deacetylates LXR, and SREBP-1c promoter transactivation by SIRT1 is abolished when LXR response elements are deleted, establishing that SIRT1 controls SREBP-1c through LXR deacetylation. SIRT1 catalytic domain knockout mice, adenoviral SIRT1 overexpression in human myotubes, LXR acetylation assays, SREBP-1c promoter deletion/reporter assays, gene electrotransfer in vivo PloS one Medium 22984430
2003 Controlled expression of nuclear active SREBP-1c (naSREBP-1c) in INS-1 beta-cells causes lipid droplet accumulation, blunts glucose-stimulated insulin secretion, and triggers cell growth arrest and apoptosis by targeting multiple genes in carbohydrate metabolism, lipid biosynthesis, and apoptosis pathways; SREBP-1c processing in beta-cells is slow and irresponsive to acute glucose/insulin unlike lipogenic tissues. Tet-On inducible expression system in INS-1 cells, gene expression profiling, functional insulin secretion assays, apoptosis assays The Journal of biological chemistry Medium 12600983
2018 ChREBP deficiency in liver reduces SREBP-1c mRNA and protein levels, and conversely, ChREBP overexpression fails to support lipogenic gene expression in Scap-deficient livers; adeno-associated virus rescue of nuclear SREBP-1c in ChREBP-KO mice normalizes lipogenic but not glycolytic genes, establishing that SREBP-1c and ChREBP are both required and act on distinct gene sets. Liver-specific ChREBP knockout mice, AAV-mediated nuclear SREBP-1c rescue, Scap-knockout epistasis, gene expression analysis Journal of lipid research High 29335275
2005 ER stress activates SREBP-1c cleavage in beta-cells independent of insulin; dominant-negative SREBP-1c prevents glucolipotoxic effects of high glucose (lipid accumulation, impaired insulin secretion, apoptosis, IRS2/Bclxl/Pdx1 downregulation), and SREBP-1 binds the human IRS2 promoter under high glucose and ER stress conditions. Dominant-negative SREBP-1c in INS-1 cells, ER stress inducers (thapsigargin, tunicamycin), SREBP-1 binding assay on IRS2 promoter in rat islets Journal of cell science Medium 16091421
2011 SREBP-1c binds to two E-box motifs in the first intron of the clusterin gene and activates its transcription in response to high glucose in primary hepatocytes; ChIP confirms glucose-induced recruitment of SREBP-1c to this intronic region. Reporter assays, chromatin immunoprecipitation in primary hepatocytes, promoter/intron deletion analysis Biochemical and biophysical research communications Medium 21549685
2022 SREBP1 positively regulates LGALS3 expression by binding its promoter; BRD2 co-immunoprecipitates with SREBP1's transcription-active domain and with both its own promoter and the Lgals3 promoter DNA, establishing a BRD2-dependent feedforward circuit; BETs inhibition abolishes cholesterol-stimulated SREBP1/LGALS3 upregulation. ChIP-qPCR, EMSA, co-immunoprecipitation of BRD2 with SREBP1, BETs inhibitor treatment in smooth muscle cells Molecular therapy. Nucleic acids Medium 35694209
2021 SREBF1 cooperates with master transcription factors TP63 and KLF5 in a feedforward co-regulatory loop to control hundreds of cis-regulatory elements across the SCC epigenome, regulating fatty acid, sphingolipid, and glycerophospholipid biosynthesis; SREBF1 is essential for SCC cell viability and migration. Loss-of-function assays, LC-MS/MS lipidomics, ChIP-seq/ATAC-seq epigenomic analysis, GSEA of patient samples Nature communications Medium 34272396
2025 PKM2 dimerization is required for SREBP1 activation and lipid droplet accumulation in microglia; pharmacological activation of TRPV1 inhibits PKM2 dimerization, reduces SREBP1 activation, and improves microglial function and Alzheimer's disease pathology in 3xTg mice. Transcriptomic analysis of isolated microglia, pharmacological TRPV1 activation (capsaicin), PKM2 dimerization inhibition, lipid droplet quantification, in vivo 3xTg mouse model Cell death & disease Medium 39809738

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Hepatic steatosis: a role for de novo lipogenesis and the transcription factor SREBP-1c. Diabetes, obesity & metabolism 555 21029304
2010 SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic lipid metabolism. The Journal of biological chemistry 449 20817729
2007 SREBP-1c transcription factor and lipid homeostasis: clinical perspective. Hormone research 301 17344645
2016 SREBP1 Contributes to Resolution of Pro-inflammatory TLR4 Signaling by Reprogramming Fatty Acid Metabolism. Cell metabolism 289 28041958
2015 The CREB coactivator CRTC2 controls hepatic lipid metabolism by regulating SREBP1. Nature 259 26147081
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
2005 ER stress and SREBP-1 activation are implicated in beta-cell glucolipotoxicity. Journal of cell science 228 16091421
2012 Insulin stimulation of SREBP-1c processing in transgenic rat hepatocytes requires p70 S6-kinase. Proceedings of the National Academy of Sciences of the United States of America 225 22927400
2019 Berberine attenuates nonalcoholic hepatic steatosis through the AMPK-SREBP-1c-SCD1 pathway. Free radical biology & medicine 220 31226399
2012 Connecting mTORC1 signaling to SREBP-1 activation. Current opinion in lipidology 210 22449814
2020 ACSL4 reprograms fatty acid metabolism in hepatocellular carcinoma via c-Myc/SREBP1 pathway. Cancer letters 191 33340617
2018 Interplay between ChREBP and SREBP-1c coordinates postprandial glycolysis and lipogenesis in livers of mice. Journal of lipid research 190 29335275
2021 CD36 promotes de novo lipogenesis in hepatocytes through INSIG2-dependent SREBP1 processing. Molecular metabolism 164 34974159
2021 SREBP-1c and lipogenesis in the liver: an update1. The Biochemical journal 123 34673919
2017 Expression of SREBP-1c Requires SREBP-2-mediated Generation of a Sterol Ligand for LXR in Livers of Mice. eLife 113 28244871
2016 Arginine Methylation of SREBP1a via PRMT5 Promotes De Novo Lipogenesis and Tumor Growth. Cancer research 112 26759235
2022 Ammonia stimulates SCAP/Insig dissociation and SREBP-1 activation to promote lipogenesis and tumour growth. Nature metabolism 111 35534729
2004 Selective coactivator interactions in gene activation by SREBP-1a and -1c. Molecular and cellular biology 109 15340088
2021 Interplay and cooperation between SREBF1 and master transcription factors regulate lipid metabolism and tumor-promoting pathways in squamous cancer. Nature communications 103 34272396
2024 Rutin ameliorated lipid metabolism dysfunction of diabetic NAFLD via AMPK/SREBP1 pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 95 38394735
2023 Regulation and targeting of SREBP-1 in hepatocellular carcinoma. Cancer metastasis reviews 86 38036934
2004 SREBP-1c mediates the insulin-dependent hepatic glucokinase expression. The Journal of biological chemistry 84 15123649
2003 The transcription factor SREBP-1c is instrumental in the development of beta-cell dysfunction. The Journal of biological chemistry 84 12600983
2021 SREBP1-induced fatty acid synthesis depletes macrophages antioxidant defences to promote their alternative activation. Nature metabolism 79 34531575
2016 Insulin induction of SREBP-1c in rodent liver requires LXRα-C/EBPβ complex. Proceedings of the National Academy of Sciences of the United States of America 68 27382175
2002 Up-regulation of SREBP-1c and lipogenic genes in skeletal muscles after exercise training. Biochemical and biophysical research communications 68 12163031
2007 Oxysterol binding protein induces upregulation of SREBP-1c and enhances hepatic lipogenesis. Arteriosclerosis, thrombosis, and vascular biology 66 17303778
2019 Salicylic acid treats acne vulgaris by suppressing AMPK/SREBP1 pathway in sebocytes. Experimental dermatology 64 30972839
2018 SREBF1 Activity Is Regulated by an AR/mTOR Nuclear Axis in Prostate Cancer. Molecular cancer research : MCR 63 29784665
2023 SREBF1/SREBP-1 concurrently regulates lipid synthesis and lipophagy to maintain lipid homeostasis and tumor growth. Autophagy 59 37927089
2020 Activation of SREBP-1c alters lipogenesis and promotes tumor growth and metastasis in gastric cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 59 32464305
2016 AMPK and SREBP-1c mediate the anti-adipogenic effect of β-hydroxyisovalerylshikonin. International journal of molecular medicine 58 26865314
2004 SREBP-1c and Sp1 interact to regulate transcription of the gene for phosphoenolpyruvate carboxykinase (GTP) in the liver. The Journal of biological chemistry 58 14744869
2023 Aberrant elevation of FTO levels promotes liver steatosis by decreasing the m6A methylation and increasing the stability of SREBF1 and ChREBP mRNAs. Journal of molecular cell biology 57 36352530
2009 Salt-inducible kinase regulates hepatic lipogenesis by controlling SREBP-1c phosphorylation. The Journal of biological chemistry 56 19244231
2015 Srebp-1 Interacts with c-Myc to Enhance Somatic Cell Reprogramming. Stem cells (Dayton, Ohio) 54 26388522
2022 The NQO1/p53/SREBP1 axis promotes hepatocellular carcinoma progression and metastasis by regulating Snail stability. Oncogene 49 36253445
2021 Hepatic deletion of Mboat7 (LPIAT1) causes activation of SREBP-1c and fatty liver. Journal of lipid research 49 32859645
2021 SREBP1/FASN/cholesterol axis facilitates radioresistance in colorectal cancer. FEBS open bio 48 33665967
2019 PGC1β Regulates Breast Tumor Growth and Metastasis by SREBP1-Mediated HKDC1 Expression. Frontiers in oncology 48 31058090
2016 SREBP-1c/MicroRNA 33b Genomic Loci Control Adipocyte Differentiation. Molecular and cellular biology 48 26830228
2020 The lncRNA Gm15622 stimulates SREBP-1c expression and hepatic lipid accumulation by sponging the miR-742-3p in mice. Journal of lipid research 47 32229588
2018 JAZF1 ameliorates age and diet-associated hepatic steatosis through SREBP-1c -dependent mechanism. Cell death & disease 47 30154417
2006 Exercise training and calorie restriction increase SREBP-1 expression and intramuscular triglyceride in skeletal muscle. American journal of physiology. Endocrinology and metabolism 44 16449296
2023 TRIM21 attenuates renal carcinoma lipogenesis and malignancy by regulating SREBF1 protein stability. Journal of experimental & clinical cancer research : CR 42 36694250
2014 SREBP-1 Mediates Angiotensin II-Induced TGF-β1 Upregulation and Glomerular Fibrosis. Journal of the American Society of Nephrology : JASN 41 25398788
2023 The roles and mechanisms of SREBP1 in cancer development and drug response. Genes & diseases 40 38560498
2019 Emodin Induced SREBP1-Dependent and SREBP1-Independent Apoptosis in Hepatocellular Carcinoma Cells. Frontiers in pharmacology 40 31297058
2020 Brown adipocyte-derived exosomal miR-132-3p suppress hepatic Srebf1 expression and thereby attenuate expression of lipogenic genes. Biochemical and biophysical research communications 37 32595040
2019 Glycerol kinase 5 confers gefitinib resistance through SREBP1/SCD1 signaling pathway. Journal of experimental & clinical cancer research : CR 37 30791926
2022 Resveratrol Inhibits Proliferation and Induces Autophagy by Blocking SREBP1 Expression in Oral Cancer Cells. Molecules (Basel, Switzerland) 36 36500345
2007 SREBP-1c and TFE3, energy transcription factors that regulate hepatic insulin signaling. Journal of molecular medicine (Berlin, Germany) 35 17279346
2022 Exosomal miR-122 promotes adipogenesis and aggravates obesity through the VDR/SREBF1 axis. Obesity (Silver Spring, Md.) 34 35170865
2022 Apolipoprotein A4 Restricts Diet-Induced Hepatic Steatosis via SREBF1-Mediated Lipogenesis and Enhances IRS-PI3K-Akt Signaling. Molecular nutrition & food research 34 35909347
2019 Critical evaluation of the DNA-methylation markers ABCG1 and SREBF1 for Type 2 diabetes stratification. Epigenomics 34 31169416
2017 Kukoamine A attenuates insulin resistance and fatty liver through downregulation of Srebp-1c. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 34 28254666
2017 PPARα-dependent Insig2a overexpression inhibits SREBP-1c processing during fasting. Scientific reports 34 28855656
2014 PAS kinase drives lipogenesis through SREBP-1 maturation. Cell reports 34 25001282
2020 The lipogenic LXR-SREBF1 signaling pathway controls cancer cell DNA repair and apoptosis and is a vulnerable point of malignant tumors for cancer therapy. Cell death and differentiation 32 32144382
2023 The Scap-SREBP1-S1P/S2P lipogenesis signal orchestrates the homeostasis and spatiotemporal activation of NF-κB. Cell reports 31 37267109
2022 Isosilybin regulates lipogenesis and fatty acid oxidation via the AMPK/SREBP-1c/PPARα pathway. Chemico-biological interactions 31 36347319
2021 miR-23a/b-3p promotes hepatic lipid accumulation by regulating Srebp-1c and Fas. Journal of molecular endocrinology 31 34723832
2021 SREBP1 promotes invasive phenotypes by upregulating CYR61/CTGF via the Hippo-YAP pathway. Endocrine-related cancer 31 34821220
2014 SREBF1 links lipogenesis to mitophagy and sporadic Parkinson disease. Autophagy 31 24991824
2023 BHLHE40 Inhibits Ferroptosis in Pancreatic Cancer Cells via Upregulating SREBF1. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 29 38064101
2019 Sterol 12α-Hydroxylase Aggravates Dyslipidemia by Activating the Ceramide/mTORC1/SREBP-1C Pathway via FGF21 and FGF15. Gene expression 29 30890204
2017 Coordinated regulation of hepatic FoxO1, PGC-1α and SREBP-1c facilitates insulin action and resistance. Cellular signalling 29 29269047
2018 SREBP-1c-Dependent Metabolic Remodeling of White Adipose Tissue by Caloric Restriction. International journal of molecular sciences 27 30373107
2017 SREBP-1c as a molecular bridge between lipogenesis and cell cycle progression of clear cell renal carcinoma. Bioscience reports 27 29138263
2013 Clusterin decreases hepatic SREBP-1c expression and lipid accumulation. Endocrinology 27 23515283
2007 SREBP-1c expression in Schwann cells is affected by diabetes and nutritional status. Molecular and cellular neurosciences 27 17632011
2023 PRP19 Enhances Esophageal Squamous Cell Carcinoma Progression by Reprogramming SREBF1-Dependent Fatty Acid Metabolism. Cancer research 24 36723974
2021 Deletion of SREBF1, a Functional Bone-Muscle Pleiotropic Gene, Alters Bone Density and Lipid Signaling in Zebrafish. Endocrinology 24 33068391
2021 SETD8 stabilized by USP17 epigenetically activates SREBP1 pathway to drive lipogenesis and oncogenesis of ccRCC. Cancer letters 24 34942305
2016 E4BP4 is an insulin-induced stabilizer of nuclear SREBP-1c and promotes SREBP-1c-mediated lipogenesis. Journal of lipid research 24 27252523
2012 Phospho-ΔNp63α/SREBF1 protein interactions: bridging cell metabolism and cisplatin chemoresistance. Cell cycle (Georgetown, Tex.) 24 22951905
2012 Sirtuin 1 regulates SREBP-1c expression in a LXR-dependent manner in skeletal muscle. PloS one 24 22984430
2002 SREBP-1: gene regulatory key to syndrome X? Annals of the New York Academy of Sciences 24 12079831
2024 CLDN6 inhibits breast cancer growth and metastasis through SREBP1-mediated RAS palmitoylation. Cellular & molecular biology letters 23 39169280
2024 Darolutamide-mediated phospholipid remodeling induces ferroptosis through the SREBP1-FASN axis in prostate cancer. International journal of biological sciences 23 39309439
1994 Sterol mediated regulation of SREBP-1a,1b,1c and SREBP-2 in cultured human cells. Biochemical and biophysical research communications 23 8060328
2025 The TRPV1-PKM2-SREBP1 axis maintains microglial lipid homeostasis in Alzheimer's disease. Cell death & disease 21 39809738
2024 Loss of SREBP-1c ameliorates iron-induced liver fibrosis by decreasing lipocalin-2. Experimental & molecular medicine 21 38622198
2021 BRG1 Links TLR4 Trans-Activation to LPS-Induced SREBP1a Expression and Liver Injury. Frontiers in cell and developmental biology 21 33816466
2023 FMO2 ameliorates nonalcoholic fatty liver disease by suppressing ER-to-Golgi transport of SREBP1. Hepatology (Baltimore, Md.) 20 37874228
2020 Srebf1 Controls Midbrain Dopaminergic Neurogenesis. Cell reports 20 32375051
2020 SREBP1 regulates mitochondrial metabolism in oncogenic KRAS expressing NSCLC. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20 32568455
2009 Induction of SREBP-1c mRNA by differentiation and LXR ligand in human keratinocytes. The Journal of investigative dermatology 20 19242521
2011 SREBP-1c regulates glucose-stimulated hepatic clusterin expression. Biochemical and biophysical research communications 19 21549685
2025 SREBF1-based metabolic reprogramming in prostate cancer promotes tumor ferroptosis resistance. Cell death discovery 17 39988626
2012 Expression of R132H mutational IDH1 in human U87 glioblastoma cells affects the SREBP1a pathway and induces cellular proliferation. Journal of molecular neuroscience : MN 17 23011765
2024 Electroacupuncture Suppresses Oxidative Stress and Ferroptosis by Activating the mTOR/SREBP1 Pathway in Ischemic Stroke. Critical reviews in immunology 15 38848297
2019 CYP1A2 contributes to alcohol-induced abnormal lipid metabolism through the PTEN/AKT/SREBP-1c pathway. Biochemical and biophysical research communications 15 30979496
2018 CVB3 Nonstructural 2A Protein Modulates SREBP1a Signaling via the MEK/ERK Pathway. Journal of virology 15 30258014
2022 SREBP1 regulates Lgals3 activation in response to cholesterol loading. Molecular therapy. Nucleic acids 14 35694209
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
2021 Impairment of ULK1 sulfhydration-mediated lipophagy by SREBF1/SREBP-1c in hepatic steatosis. Autophagy 13 34455909
2018 Impact of silencing hepatic SREBP-1 on insulin signaling. PloS one 13 29723221
2025 Lipid metabolism reprograming by SREBP1-PCSK9 targeting sensitizes pancreatic cancer to immunochemotherapy. Cancer communications (London, England) 12 40439109
2024 USP11 promotes lipogenesis and tumorigenesis by regulating SREBF1 stability in hepatocellular carcinoma. Cell communication and signaling : CCS 12 39558331

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