Affinage

KLF11

Krueppel-like factor 11 · UniProt O14901

Length
512 aa
Mass
55.1 kDa
Annotated
2026-06-10
86 papers in source corpus 37 papers cited in narrative 37 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

KLF11 is an Sp1/KLF-family zinc finger transcription factor that binds GC-rich (Sp1-like) DNA elements and functions as a context-dependent repressor or activator, positioning it at the intersection of TGF-β signaling, oxidative stress, metabolic homeostasis, and ferroptosis control (PMID:9748269, PMID:12970187, PMID:15300592). Its repressive activity depends on an N-terminal Mad1-like Sin3-interacting domain (SID) that recruits the mSin3A/HDAC corepressor complex to silence targets such as SOD2 and Catalase1, Smad7, CYP3A4, and glycodelin-A (PMID:12006497, PMID:12970187, PMID:24060634, PMID:25076120); nuclear localization is conferred by bipartite NLS sequences within its zinc finger DNA-binding domain, which alone can activate transcription (PMID:17252542). This SID-mSin3A interaction is the principal regulated node: EGF–Ras–MEK–ERK phosphorylation of serine/threonine sites flanking the SID disrupts corepressor binding and abolishes repression, a switch exploited in oncogenic-Ras pancreatic cancer to relieve KLF11-mediated repression of Smad7 and, with Smad3, of c-myc (PMID:12006497, PMID:15300592, PMID:17114344). As an activator KLF11 engages coactivators including p300 and PPARγ to transactivate metabolic and developmental targets, driving insulin and Pdx-1 expression in beta cells, UCP1 and the brite/brown adipocyte program, hepatic PPARα-dependent fatty acid oxidation, and ABCA1/G1 (PMID:15774581, PMID:19843526, PMID:20709022, PMID:23183531, PMID:25504365, PMID:40397286). KLF11 enforces vascular homeostasis by repressing tissue factor (F3) in smooth muscle and endothelial cells—partly by blocking EGR1 promoter binding—and by limiting EC inflammation and ROS to suppress thrombosis and abdominal aortic aneurysm (PMID:30602303, PMID:34428834, PMID:33507881). In tumor and tissue-protective contexts it represses GPX4 and FSP1 to promote ferroptosis, suppresses YAP/TEAD output via SIN3A/HDAC recruitment, and modulates p53 through MDM2 interaction (PMID:33571129, PMID:37248295, PMID:38725840, PMID:38810862). KLF11 protein and locus abundance are themselves controlled by SKP2-mediated K48 ubiquitination and proteasomal degradation and by epigenetic activation/silencing of the KLF11 enhancer (PMID:33571129, PMID:38690715, PMID:38503899).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1998 High

    Established KLF11 as a nuclear, sequence-specific transcription factor, defining its core biochemical identity as an Sp1-like GC-box binder that represses transcription and restrains proliferation.

    Evidence Nuclear fractionation, in vitro DNA-binding, luciferase reporter, and proliferation assays in CHO cells

    PMID:9748269

    Open questions at the time
    • Did not identify the corepressor machinery or physiological target genes
    • Repression mechanism at endogenous loci not yet defined
  2. 1999 Medium

    Showed KLF11 can also act as an activator, binding the CACCC box to enhance gamma/epsilon-globin transcription, foreshadowing its dual repressor/activator behavior.

    Evidence CACCC-box deletion reporter assays and endogenous globin expression in K562 erythroid cells

    PMID:10207080

    Open questions at the time
    • Coactivator partners not identified
    • Physiological role in erythropoiesis not tested in vivo
  3. 2002 High

    Identified the molecular basis of KLF11 repression and its regulation: the Mad1-like SID recruits mSin3A, and ERK phosphorylation of SID-flanking residues disrupts this interaction, defining a MAPK-controlled repression switch.

    Evidence Co-IP, site-directed mutagenesis, in vitro kinase assay, reporter assay

    PMID:12006497

    Open questions at the time
    • Endogenous genes regulated by this switch not yet known
    • HDAC recruitment downstream of mSin3A not directly shown here
  4. 2003 High

    Linked KLF11 repression to oxidative stress and tumor suppression by showing SID-mSin3A-dependent silencing of SOD2 and Catalase1 sensitizes cells to oxidative stress, with rescue confirming causality.

    Evidence ChIP, adenoviral SOD2/Catalase1 rescue, transgenic mouse, growth/transformation assays

    PMID:12970187

    Open questions at the time
    • Whether antioxidant repression underlies all tumor-suppressive effects unresolved
    • Tissue specificity of these targets not mapped
  5. 2004 High

    Connected KLF11 to TGF-β signal amplification and oncogenic Ras: KLF11 represses Smad7 to potentiate TGF-β, and ERK disrupts this in Ras-transformed pancreatic cancer.

    Evidence Reporter, qPCR, Co-IP, in vitro ERK phosphorylation, ERK-insensitive mutant rescue

    PMID:15300592

    Open questions at the time
    • In vivo demonstration in pancreatic tumors not provided
    • Crosstalk with canonical Smad complexes only partly defined
  6. 2004 High

    Extended the repressor/activator duality to lipid-regulated and neurotransmitter loci, with KLF11 acting as a cholesterol-sensitive caveolin-1 repressor and a dual regulator of MAO B.

    Evidence RNAi, ChIP, EMSA, reporter assays (caveolin-1); reporter, EMSA, ChIP, enzymatic activity (MAO B)

    PMID:15024015 PMID:15531587

    Open questions at the time
    • Mechanism determining activator vs repressor outcome at adjacent elements not fully resolved
    • In vivo relevance of caveolin-1/MAO B regulation untested here
  7. 2005 High

    Established KLF11 as a glucose-inducible activator of the insulin gene and revealed a disease-relevant variant (Gln62Arg) that impairs mSin3A binding and insulin promoter activation.

    Evidence Oligonucleotide binding, EMSA, reporter assay, ChIP in pancreatic beta cells

    PMID:15774581

    Open questions at the time
    • How a corepressor-binding variant affects an activation function not mechanistically reconciled
    • Beta-cell coactivators for insulin activation not identified here
  8. 2006 High

    Defined a direct KLF11-Smad3 interaction that cooperatively represses c-myc via the TGF-β inhibitory element, disrupted by ERK in oncogenic-Ras cells, deepening the growth-suppression mechanism.

    Evidence Co-IP, GST pulldown, reporter, DNA binding, RNAi, U0126 ERK inhibition

    PMID:17114344

    Open questions at the time
    • Structural basis of KLF11-Smad3 complex unknown
    • Whether other TIE-containing genes are co-regulated not addressed
  9. 2007 Medium

    Mapped KLF11 functional domains and nuclear targeting, showing the N-terminal SID is required for repression and apoptosis while the zinc finger DBD carries bipartite NLS sequences and intrinsic activation capacity.

    Evidence GAL4 reporter assays, EGFP-fusion live imaging, NLS mutation mapping; OLI-neu apoptosis/Bcl-XL assays

    PMID:17252542 PMID:17308981

    Open questions at the time
    • NLS-binding import machinery not identified
    • Generality of pro-apoptotic role beyond oligodendroglial cells untested
  10. 2008 Medium

    Tied KLF11's pro-apoptotic activity to Smad7 repression in glial cells, showing the SID-dependent disruption of TGF-β negative feedback drives apoptosis.

    Evidence Domain-deletion mutants, Smad7 reporter assay, caspase-3 apoptosis assay in OLI-neu cells

    PMID:18189266

    Open questions at the time
    • In vivo neural phenotype not established
    • Single cell-line system
  11. 2009 High

    Identified p300 as a KLF11 coactivator engaged through the zinc finger domain to activate Pdx-1, providing a molecular basis for KLF11's activator function in beta cells.

    Evidence Oligonucleotide binding, ChIP at Pdx-1 Area II, GC1/GC2 mutation reporters, in vivo Co-IP with p300

    PMID:19843526

    Open questions at the time
    • Determinants selecting p300 vs mSin3A recruitment unresolved
    • In vivo beta-cell requirement not tested here
  12. 2010 High

    Expanded KLF11's activator role into thermogenic and antiproliferative programs, activating UCP1 during brown adipogenesis and mediating progesterone-receptor-coupled suppression of leiomyoma proliferation.

    Evidence UCP1 reporter/ChIP and brown adipocyte differentiation; ChIP-cloning, siRNA, reporter, proliferation assays (PR/leiomyoma)

    PMID:20124487 PMID:20709022

    Open questions at the time
    • Coactivators driving UCP1 activation not defined
    • PR-KLF11 physical interaction not directly shown
  13. 2012 High

    Established KLF11 as a stress- and hormone-responsive activator of monoamine oxidases and metabolic genes, linking glucocorticoid-induced nuclear translocation to MAO A and identifying PPARα-dependent control of hepatic fatty acid oxidation.

    Evidence KO mice, nuclear/cytoplasmic fractionation, MAO A reporter/activity, stress model; adenoviral gain/loss and PPARα-knockdown epistasis in liver

    PMID:22628545 PMID:23183531

    Open questions at the time
    • Signal triggering cytoplasm-to-nucleus translocation not defined
    • Direct vs indirect PPARα target engagement not fully separated
  14. 2013 High

    Defined KLF11 as a direct PPARγ co-regulator and target, and broadened its repressive ECM/fibrosis program, integrating metabolic, cerebrovascular-protective, and endometriotic-fibrotic roles.

    Evidence Co-activation screen, Co-IP, KO mouse stroke model; ChIP of collagen/MMP/TGF-β promoters in KO endometriosis model; glycodelin SIN3/HDAC recruitment

    PMID:23408111 PMID:23555910 PMID:24060634

    Open questions at the time
    • Reciprocal PPARγ-KLF11 feedback dynamics not fully quantified
    • Mechanism switching KLF11 between fibrotic-gene repression and metabolic activation unresolved
  15. 2014 High

    Cemented KLF11's role in glucose/lipid homeostasis and drug metabolism, showing PPARγ feed-forward control of adipocyte browning, repression of hepatic gluconeogenic genes, and SIN3A/HDAC-dependent CYP3A4 silencing.

    Evidence ChIP-seq for PPARγ superenhancers and mitochondrial assays; adenoviral hepatocyte gain/loss; CYP3A4 ChIP, SID-mutation and HDAC-inhibitor reversal

    PMID:24586865 PMID:25076120 PMID:25504365

    Open questions at the time
    • How a single factor coordinates opposing metabolic programs across tissues not mechanistically unified
    • Gluconeogenic-gene repression mechanism (direct vs PGC-1α-mediated) only partly defined
  16. 2017 Medium

    Detailed the TGF-β–KLF11 regulatory loop and an additional activator target (DRD2) in endometriosis, showing non-canonical TGF-β1 control of KLF11 and its downstream Cyp3a/Drd2 outputs.

    Evidence KO mouse endometriosis models with TGFβR1 inhibitor; ChIP and reporter for DRD2

    PMID:27384304 PMID:28372535

    Open questions at the time
    • Non-SMAD signaling controlling KLF11 expression not defined
    • Single-lab endometriosis system
  17. 2021 High

    Established KLF11 as a vascular protective factor and a YAP/TEAD antagonist, repressing tissue factor in SMCs and ECs (including via EGR1 displacement), suppressing thrombosis and aneurysm, and forming a YAP/TEAD negative-feedback loop broken by epigenetic KLF11 silencing.

    Evidence ChIP, Co-IP (KLF11-EGR1; KLF11-YAP/TEAD), tissue-specific KO mice (thrombosis, DVT, AAA), CRISPR screen in sarcoma

    PMID:30602303 PMID:33507881 PMID:33571129 PMID:34428834

    Open questions at the time
    • How SID-mSin3A recruitment to YAP/TEAD sites is targeted not fully resolved
    • Relationship between vascular and oncogenic YAP roles not integrated
  18. 2023 High

    Identified KLF11 as a driver of ferroptosis by directly repressing GPX4 in lung adenocarcinoma, increasing chemosensitivity and adding ferroptosis to its tumor-suppressive repertoire.

    Evidence ChIP-seq, ChIP-qPCR, dual luciferase, RNA-seq, GPX4 rescue, in vitro and in vivo overexpression/knockout

    PMID:37248295

    Open questions at the time
    • Whether GPX4 repression uses the SID/mSin3A axis not shown
    • Generality across other ferroptosis-sensitive tumors untested here
  19. 2024 Medium

    Extended KLF11 ferroptosis control to cardiomyocytes via FSP1 repression and revealed protein-level and locus-level regulation through SKP2-mediated degradation and HP1γ-driven enhancer activation, plus an MDM2-dependent p53 suppression mechanism in cancer.

    Evidence AAV9 cardiac models and FSP1 rescue; Co-IP/ubiquitination for SKP2-KLF11; ChIP of HP1γ at Klf11 enhancer; Co-IP and ubiquitination for KLF11-MDM2-p53

    PMID:38503899 PMID:38690715 PMID:38725840 PMID:38810862

    Open questions at the time
    • Signals coupling SKP2 activity to KLF11 turnover in disease contexts unclear
    • How KLF11 (a repressor) raises MDM2 and lowers TP53 mRNA mechanistically not fully resolved
  20. 2025 Medium

    Integrated KLF11 into macrophage immunometabolism and atheroprotection through a KLF11-PPARα-YAP1 complex that suppresses glycolysis and activates cholesterol-efflux transporters ABCA1/G1.

    Evidence KO mouse atherosclerosis model, Co-IP defining ternary complex, reporter assays, macrophage gain/loss of function

    PMID:40397286

    Open questions at the time
    • Stoichiometry and DNA-binding architecture of the ternary complex undefined
    • Single-lab finding
  21. 2026 Medium

    Positioned KLF11 as a downstream effector of nuclear-receptor (FXR) signaling in renoprotection and as a determinant of DNA-repair-driven radioresistance, broadening its roles into anti-inflammatory and genome-maintenance contexts.

    Evidence FXR ChIP/reporter and genetic KO with JAK2/STAT3 analysis (kidney); Co-IP/IF for KLF11-MDM2, comet and colony assays, xenograft (esophageal cancer)

    PMID:41655531 PMID:41855776

    Open questions at the time
    • Direct vs indirect KLF11 control of JAK2/STAT3 not resolved
    • MDM2-E2F1-RAD51 axis defined in a single tumor system only

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved what governs the genome-wide choice between KLF11's repressor (SID-mSin3A/HDAC) and activator (p300/PPARγ) modes at a given GC-rich locus and across tissues.
  • No unifying model linking phosphorylation state, cofactor availability, and local chromatin to activation vs repression
  • No structural model of KLF11 in repressor vs activator complexes
  • Tissue-specific cofactor partners only partially catalogued

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 6 GO:0098772 molecular function regulator activity 4 GO:0140096 catalytic activity, acting on a protein 4
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 1
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1430728 Metabolism 4 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-109582 Hemostasis 2
Partners
EGR1EP300MDM2PPARAPPARGSIN3ASMAD3YAP1
Complex memberships
SIN3A/HDAC corepressor complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 KLF11 (TIEG2) is a nuclear protein that specifically binds to Sp1-like (GC-rich) DNA sequences in vitro and represses promoters containing Sp1-like binding sites; overexpression inhibits cell proliferation in CHO cells. Nuclear fractionation, in vitro DNA-binding assay, luciferase reporter assay, [3H]thymidine/MTS proliferation assays The Journal of biological chemistry High 9748269
1999 KLF11 (FKLF) acts as a transcriptional activator of the gamma- and epsilon-globin gene promoters via the CACCC box in erythroid cells; transfection of KLF11 cDNA into K562 cells enhanced endogenous epsilon- and gamma-globin gene expression. Luciferase reporter assay with CACCC box deletion constructs, transfection into K562 erythroid cells Molecular and cellular biology Medium 10207080
2002 The Mad1-like Sin3-interacting domain (SID) of KLF11 (TIEG2) binds mSin3A to mediate transcriptional repression; this interaction is disrupted by EGF-Ras-MEK1-ERK2 signaling via phosphorylation of four serine/threonine sites adjacent to the SID, thereby inhibiting KLF11's repression activity. Co-immunoprecipitation, site-directed mutagenesis, in vitro kinase assay, reporter assay The EMBO journal High 12006497
2003 KLF11 represses transcription of SOD2 and Catalase1 promoters via its Mad1-like SID-mSin3A interaction; this repression renders cells more sensitive to oxidative stress, an effect rescuable by adenoviral SOD2/Catalase1 re-expression. KLF11 also inhibits neoplastic transformation and cell growth in vitro and in vivo. Chromatin immunoprecipitation (ChIP), adenoviral rescue experiment, transgenic mouse model, cell growth/transformation assays The EMBO journal High 12970187
2004 KLF11 represses Smad7 transcription by recruiting mSin3A via GC-rich sites on the Smad7 promoter, thereby potentiating TGF-β signaling. In pancreatic cancer cells with oncogenic Ras, ERK phosphorylates KLF11 and disrupts KLF11-mSin3A interaction; an ERK-insensitive KLF11 mutant restores mSin3A binding and Smad7 repression. Reporter assay, real-time PCR, co-immunoprecipitation, in vitro ERK phosphorylation, site-directed mutagenesis Gastroenterology High 15300592
2004 KLF11 binds to an Sp1 site flanking the SRE in the caveolin-1 promoter and acts as a dominant repressor. Cholesterol depletion displaces KLF11 from this site (via down-regulation of KLF11 expression and competition by Sp1), enabling SREBP/Sp1-mediated activation of caveolin-1 transcription. RNA interference, chromatin immunoprecipitation, EMSA, luciferase reporter assay The Journal of biological chemistry High 15531587
2004 KLF11 (TIEG2) acts as a transcriptional activator of MAO B gene expression via Sp1 sites, and as a repressor at the CACCC element; gel-shift and ChIP confirmed direct binding to both elements in the MAO B core promoter. Cotransfection reporter assays, gel-shift (EMSA), chromatin immunoprecipitation, RT-PCR, western blot, MAO B catalytic activity assay The Journal of biological chemistry High 15024015
2005 KLF11 binds the insulin promoter at GC-rich sites and activates its transcriptional activity in pancreatic beta cells, as a glucose-inducible regulator. The Gln62Arg variant impairs mSin3A-binding activity of KLF11 and reduces insulin promoter activation. Random oligonucleotide binding assay, EMSA, luciferase reporter assay, chromatin immunoprecipitation Proceedings of the National Academy of Sciences of the United States of America High 15774581
2006 KLF11 cooperates with Smad3 to repress c-myc transcription via the TGF-β inhibitory element (TIE) in the c-myc promoter; ERK hyperactivation in pancreatic cancer cells with oncogenic Ras disrupts KLF11-Smad3 complex formation and KLF11-Smad3 binding to the TIE, preventing c-myc repression and growth inhibition. Co-immunoprecipitation, GST pulldown, reporter assay, DNA binding assay, RNA interference, U0126 ERK inhibitor treatment Molecular cancer research : MCR High 17114344
2007 KLF11 (TIEG2) induces caspase-3-dependent apoptosis in oligodendroglial OLI-neu cells and decreases Bcl-XL levels by repressing the Bcl-XL promoter; the N-terminal repression domains (including the SID) are required for pro-apoptotic activity. Overexpression in OLI-neu cells, caspase-3 activation assay, western blot (Bcl-XL), reporter assay with Bcl-XL promoter Journal of neural transmission Medium 17308981
2007 The amino-terminus of KLF11 (Tieg3) is essential for transcriptional repression; the SID within this domain is required for repressive activity. The zinc finger DNA-binding domain (DBD) alone can activate transcription and contains two closely located putative bipartite nuclear localization signals (NLS) within the second and third zinc fingers that are necessary and sufficient for nuclear localization. GAL4-based luciferase assays, EGFP-fusion protein localization (live imaging), NLS deletion/mutation mapping Journal of cellular biochemistry Medium 17252542
2008 KLF11 (Tieg3) enhances TGF-β signaling in oligodendroglial cells by transcriptionally repressing Smad7, disrupting the negative feedback loop; loss of the N-terminal repression domains (including SID) abolishes both the pro-apoptotic function and Smad7 repression. Overexpression/deletion mutants in OLI-neu cells, reporter assay on Smad7 promoter, apoptosis/caspase-3 assay Journal of cellular biochemistry Medium 18189266
2009 KLF11 activates Pdx-1 transcription in pancreatic beta cells through two evolutionarily conserved GC-rich elements (GC1 and GC2) in the Pdx-1 Area II control region; KLF11 associates with Area II by ChIP and interacts with the coactivator p300 via its zinc finger domain in vivo to mediate this activation. Random oligonucleotide binding analysis, ChIP, luciferase reporter assay with GC1/GC2 mutations, co-immunoprecipitation (in vivo interaction with p300) The Journal of biological chemistry High 19843526
2010 KLF11 directly binds the UCP1 promoter via GC-box elements and activates UCP1 transcription; KLF11 is required for UCP1 expression during brown adipocyte differentiation of muBM3.1 mesenchymal stem cells. Reporter assay with UCP1 promoter, ChIP/DNA binding assay, brown adipocyte differentiation model Biochemical and biophysical research communications Medium 20709022
2010 KLF11 integrates progesterone receptor (PR) signaling to inhibit uterine leiomyoma cell proliferation. PR knockdown increases KLF11 expression; KLF11 knockdown abolishes the antiproliferative effect of RU486. KLF11 basal promoter and a distal PR-binding region (20.5 kb upstream) containing Sp1 sites (not classical PREs) recruit Sp1, RNA Pol II, PR, SRC-1 and SRC-2. ChIP-cloning to identify PR-binding site, luciferase reporter assay, siRNA knockdown of PR and KLF11, proliferation assay Cancer research High 20124487
2012 Glucocorticoids (dexamethasone) induce KLF11 mRNA and protein in neurons; KLF11 then translocates from cytoplasm to nucleus and activates the MAO A promoter via Sp/KLF-binding sites, increasing MAO A mRNA and enzymatic activity. KLF11 knockout mice show reduced brain cortex MAO A expression; chronic social defeat stress activates the KLF11 pathway in rat brain with increased MAO A. siRNA knockdown, KLF11 overexpression, KLF11 knockout mice, nuclear/cytoplasmic fractionation, MAO A promoter reporter, MAO A catalytic activity assay, in vivo stress model The Journal of biological chemistry High 22628545
2012 KLF11 overexpression in mouse livers activates the PPARα signaling pathway to improve fatty liver by promoting fatty acid oxidation; KLF11 knockdown decreases fatty acid oxidation and raises hepatic TG levels. PPARα knockdown abolishes KLF11's effects on fatty acid oxidation genes and hepatic TG. Adenoviral overexpression/shRNA in db/db and DIO mice, histology, biochemical TG assay, epistasis by co-injection with Ad-shPPARα Journal of hepatology High 23183531
2013 KLF11 interacts with PPARγ and acts as a novel PPARγ co-regulator; KLF11 is also a direct transcriptional target of PPARγ. KLF11 deficiency abolishes pioglitazone-mediated cerebrovascular protection and PPARγ transcriptional suppression of pro-apoptotic miR-15a in endothelial cells. Genome-wide co-activation screen, co-immunoprecipitation, KLF11 knockout mouse, oxygen-glucose deprivation cell model, MCAO stroke model Brain : a journal of neurology High 23408111
2013 KLF11 binds specific GC-rich promoter elements of collagen, MMP, and TGF-β family genes in endometrial stromal cells and represses their transcription; KLF11 deficiency in mice leads to large fibrotic endometriotic lesions resembling advanced human disease. ChIP of endometrial stromal cell promoters, Klf11 knockout mouse endometriosis model, comparison with Klf9 knockout PloS one High 23555910
2013 KLF11 epigenetically represses glycodelin-A expression in endometrial cells by binding two regulatory elements in the glycodelin promoter and recruiting the SIN3/HDAC corepressor complex, resulting in transcriptional repression. ChIP, reporter assay, mRNA and protein expression analysis, SIN3/HDAC corepressor recruitment assay Reproductive sciences Medium 24060634
2014 KLF11 is required for rosiglitazone-induced browning of human adipocytes; it is directly induced by PPARγ and cooperates with PPARγ in a feed-forward manner to activate the brite-selective gene program and increase mitochondrial oxidative capacity. KLF11 is associated with PPARγ superenhancers selective for brite adipocytes. siRNA knockdown of KLF11 in human adipocytes, ChIP-seq for PPARγ superenhancers, mitochondrial oxidative capacity measurement, gene expression profiling Genes & development High 25504365
2014 KLF11 binds CYP3A4 promoter GC elements and recruits SIN3A/HDAC corepressor, causing selective histone deacetylation of the CYP3A4 promoter and repressing CYP3A4 mRNA, protein, and enzymatic activity in endometrial cells. A KLF11 mutation abrogating cofactor recruitment reverses this repression. ChIP (KLF11 at CYP3A4 promoter), SIN3A/HDAC corepressor co-localization, reporter assay, mRNA/protein/enzyme activity assays, HDAC inhibitor pharmacological reversal, SID-mutation rescue Endocrinology High 25076120
2014 KLF11 suppresses hepatic gluconeogenesis by repressing PEPCK-C and PGC-1α gene expression in primary hepatocytes; adenoviral overexpression of KLF11 in diabetic mouse livers improves hyperglycemia, while KLF11 knockdown impairs glucose tolerance. Adenoviral overexpression/knockdown in primary mouse hepatocytes and in vivo mouse models, glucose output assay, gene expression analysis PloS one Medium 24586865
2016 TGF-β1 causes non-canonical (non-SMAD-mediated) transient up-regulation then sustained repression of KLF11, while KLF11 epigenetically represses CYP3A4 via SIN3A/HDAC. KLF11-deficient mice treated with TGF-β receptor inhibitor show reduced endometriotic progression and Cyp3a expression. Klf11 knockout mouse endometriosis model, TGFβR1 inhibitor treatment, histone acetyltransferase inhibitor, Cyp3a expression analysis Endocrinology Medium 27384304
2017 KLF11 binds to the DRD2 promoter and transcriptionally activates DRD2 in endometrial cells; in Klf11-/- mice with endometriosis, lesions show progressive fibrosis and decreased Drd2 expression consistent with loss of KLF11-mediated activation. ChIP, promoter reporter assay, Klf11-/- mouse endometriosis model, gene expression analysis Reproductive sciences Medium 28372535
2019 KLF11 transcriptionally suppresses the tissue factor (F3) gene in vascular smooth muscle cells via direct promoter binding (ChIP), reducing arterial thrombosis. Smooth muscle cell-specific Klf11 KO mice show reduced occlusion time in ferric chloride thrombosis model, not rescued by bone marrow transplant. Reporter assay, ChIP, siRNA knockdown and adenoviral overexpression in human aortic smooth muscle cells, conditional SMC-specific KO mouse, ferric chloride thrombosis model Arteriosclerosis, thrombosis, and vascular biology High 30602303
2021 In venous endothelial cells under prothrombotic conditions, KLF11 reduces TNF-α-induced tissue factor (TF) gene transcription by inhibiting EGR1 binding to the TF promoter, as demonstrated by reporter assay, ChIP, and co-immunoprecipitation. Klf11 KO mice are more susceptible to stasis-induced DVT. Reporter gene assay, ChIP, co-immunoprecipitation (KLF11-EGR1), gain- and loss-of-function in ECs, Klf11 KO mouse deep vein thrombosis model Thrombosis and haemostasis High 34428834
2021 KLF11 and YAP/TEAD bind adjacent DNA sites and directly interact; KLF11 recruits SIN3A/HDAC to suppress YAP/TEAD transcriptional output, while YAP/TEAD promotes KLF11 transcription, forming a negative feedback loop that is broken by epigenetic silencing of KLF11 in sarcoma cancer stem cells. Genome-wide CRISPR-Cas9 screen, co-immunoprecipitation (KLF11-YAP/TEAD), ChIP, KLF11 overexpression/knockdown, in vitro and in vivo functional assays Science advances High 33571129
2021 Endothelial KLF11 deficiency aggravates AAA formation, while EC-selective overexpression inhibits it. KLF11 inhibits EC inflammatory response, suppresses MMP9 expression and activity, and reduces NADPH oxidase 2-mediated ROS in ECs; KLF11-deficient ECs also induce smooth muscle cell dedifferentiation and apoptosis. EC-specific KLF11 transgenic and knockout mice, elastase- and PCSK9/AngII-induced AAA mouse models, gain- and loss-of-function in cultured ECs JCI insight High 33507881
2023 KLF11 binds the GPX4 promoter region and represses its transcription in lung adenocarcinoma cells, promoting ferroptosis and increasing chemosensitivity; ChIP-seq and ChIP-qPCR confirmed GPX4 as a direct KLF11 target, and GPX4 restoration antagonized KLF11-induced ferroptosis. ChIP-seq, ChIP-qPCR, dual luciferase assay, RNA-seq, KLF11 overexpression/knockout in vitro and in vivo Communications biology High 37248295
2024 KLF11 promotes ferroptosis in cardiomyocytes by suppressing FSP1 transcription; KLF11 is induced by sorafenib and its overexpression or FSP1 knockdown both increase ferroptotic cell death. Cardiac-specific AAV9-mediated KLF11 silencing or FSP1 overexpression improved cardiac dysfunction in sorafenib-treated mice. Transcriptome profiling, KLF11 overexpression/knockdown in cardiomyocytes, AAV9 cardiac-specific delivery in mice, FSP1 rescue experiment, GPX4 epistasis International journal of biological sciences Medium 38725840
2024 SKP2 E3 ubiquitin ligase triggers K48-linked ubiquitination and proteasomal degradation of KLF11 in chondrocytes; loss of KLF11 transcriptionally activates JMJD3, which demethylates H3K27me3 to activate NOTCH1, promoting OA progression. KLF11 overexpression in vivo delays OA development. Co-immunoprecipitation (SKP2-KLF11), ubiquitination assay, ChIP (KLF11 on JMJD3 promoter), H3K27me3 analysis, in vivo rat OA model FASEB journal Medium 38690715
2024 CGRP increases phosphorylated HP1γ (p-HP1γ) recruitment to the Klf11 enhancer (confirmed by ChIP), which epigenetically activates KLF11 expression; increased KLF11 in turn activates MAOB, depleting dopamine in the dorsal hippocampus and inducing anxiety-like behaviors. Chromatin immunoprecipitation (HP1γ at Klf11 enhancer), intracerebroventricular CGRP injection, MAOB pharmacological inhibition and knockdown in mice Communications biology Medium 38503899
2024 KLF11 promotes breast cancer cell proliferation by reducing TP53 mRNA transcription and by interacting with MDM2 protein to inhibit MDM2 ubiquitination/degradation, thereby increasing MDM2 levels and accelerating ubiquitin-mediated p53 proteolysis and reducing CDKN1A/BAX/NOXA1. Co-immunoprecipitation (KLF11-MDM2), ubiquitination assay, RT-qPCR, western blot, in vivo xenograft Cellular signalling Medium 38810862
2025 KLF11 forms a transcriptional complex with PPARα and YAP1 in macrophages; KLF11 suppresses PPARα-YAP1-mediated glycolysis and acts as a transcriptional activator of ABCA1/G1. KLF11 knockout abolishes wogonin's inhibitory effect on glycolysis and atherosclerosis. KLF11 KO mouse atherosclerosis model, co-immunoprecipitation (KLF11-PPARα-YAP1 complex), reporter assay, gain- and loss-of-function in macrophages Advanced science Medium 40397286
2026 FXR directly binds to a FXRE sequence in the KLF11 promoter (confirmed by luciferase reporter and ChIP) and transcriptionally upregulates KLF11; KLF11 then suppresses the JAK2/STAT3 pathway to reduce renal inflammation and apoptosis in contrast-induced AKI. FXR or KLF11 genetic deletion abolishes FXR agonist (CDCA) renoprotection. Luciferase reporter assay, ChIP (FXR at KLF11 promoter), KLF11 knockdown and FXR KO models, JAK2/STAT3 pathway analysis International immunopharmacology Medium 41855776
2026 KLF11 promotes MDM2 expression, which inhibits E2F1 ubiquitination and stabilizes E2F1, enhancing RAD51-mediated homologous recombination DNA repair and conferring radioresistance in esophageal cancer cells. Co-immunoprecipitation and immunofluorescence confirmed KLF11-MDM2 protein interaction. Co-immunoprecipitation, immunofluorescence, neutral comet assay, colony formation/apoptosis assays, in vivo xenograft, RT-qPCR/western blot Pathology, research and practice Medium 41655531

Source papers

Stage 0 corpus · 86 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Role of transcription factor KLF11 and its diabetes-associated gene variants in pancreatic beta cell function. Proceedings of the National Academy of Sciences of the United States of America 186 15774581
1998 Molecular cloning and characterization of TIEG2 reveals a new subfamily of transforming growth factor-beta-inducible Sp1-like zinc finger-encoding genes involved in the regulation of cell growth. The Journal of biological chemistry 168 9748269
2014 Browning of human adipocytes requires KLF11 and reprogramming of PPARγ superenhancers. Genes & development 138 25504365
2003 An mSin3A interaction domain links the transcriptional activity of KLF11 with its role in growth regulation. The EMBO journal 93 12970187
1999 FKLF, a novel Krüppel-like factor that activates human embryonic and fetal beta-like globin genes. Molecular and cellular biology 90 10207080
2013 KLF11 mediates PPARγ cerebrovascular protection in ischaemic stroke. Brain : a journal of neurology 87 23408111
2009 MODY7 gene, KLF11, is a novel p300-dependent regulator of Pdx-1 (MODY4) transcription in pancreatic islet beta cells. The Journal of biological chemistry 86 19843526
2012 Mechanistic role for a novel glucocorticoid-KLF11 (TIEG2) protein pathway in stress-induced monoamine oxidase A expression. The Journal of biological chemistry 76 22628545
2004 KLF11 mediates a critical mechanism in TGF-beta signaling that is inactivated by Erk-MAPK in pancreatic cancer cells. Gastroenterology 73 15300592
2011 Klf10 and Klf11 as mediators of TGF-beta superfamily signaling. Cell and tissue research 70 21574058
2010 Transcription factor KLF11 integrates progesterone receptor signaling and proliferation in uterine leiomyoma cells. Cancer research 69 20124487
2000 FKLF-2: a novel Krüppel-like transcriptional factor that activates globin and other erythroid lineage genes. Blood 69 10828046
2004 Dual functions of transcription factors, transforming growth factor-beta-inducible early gene (TIEG)2 and Sp3, are mediated by CACCC element and Sp1 sites of human monoamine oxidase (MAO) B gene. The Journal of biological chemistry 61 15024015
2022 Evaluation of Evidence for Pathogenicity Demonstrates That BLK, KLF11, and PAX4 Should Not Be Included in Diagnostic Testing for MODY. Diabetes 58 35108381
2012 Mouse KLF11 regulates hepatic lipid metabolism. Journal of hepatology 55 23183531
2004 KLF11-mediated repression antagonizes Sp1/sterol-responsive element-binding protein-induced transcriptional activation of caveolin-1 in response to cholesterol signaling. The Journal of biological chemistry 53 15531587
2006 The tumor suppressor KLF11 mediates a novel mechanism in transforming growth factor beta-induced growth inhibition that is inactivated in pancreatic cancer. Molecular cancer research : MCR 49 17114344
2002 Signaling disrupts mSin3A binding to the Mad1-like Sin3-interacting domain of TIEG2, an Sp1-like repressor. The EMBO journal 46 12006497
2010 Transcriptional regulation of a brown adipocyte-specific gene, UCP1, by KLF11 and KLF15. Biochemical and biophysical research communications 41 20709022
2013 A novel role of the Sp/KLF transcription factor KLF11 in arresting progression of endometriosis. PloS one 39 23555910
2005 Functional study of transcription factor KLF11 by targeted gene inactivation. Blood cells, molecules & diseases 39 15607700
2023 KLF11 regulates lung adenocarcinoma ferroptosis and chemosensitivity by suppressing GPX4. Communications biology 38 37248295
2021 KLF11 protects against abdominal aortic aneurysm through inhibition of endothelial cell dysfunction. JCI insight 37 33507881
2018 MicroRNA-10b regulates epithelial-mesenchymal transition by modulating KLF4/KLF11/Smads in hepatocellular carcinoma. Cancer cell international 34 29375271
2018 microRNA-30d mediated breast cancer invasion, migration, and EMT by targeting KLF11 and activating STAT3 pathway. Journal of cellular biochemistry 32 29923255
2021 Genome-wide CRISPR-Cas9 screen identified KLF11 as a druggable suppressor for sarcoma cancer stem cells. Science advances 31 33571129
2008 Tieg3/Klf11 induces apoptosis in OLI-neu cells and enhances the TGF-beta signaling pathway by transcriptional repression of Smad7. Journal of cellular biochemistry 31 18189266
2020 The Distinct Roles of Transcriptional Factor KLF11 in Normal Cell Growth Regulation and Cancer as a Mediator of TGF-β Signaling Pathway. International journal of molecular sciences 29 32331236
2014 Evidence revealing deregulation of the KLF11-MAO A pathway in association with chronic stress and depressive disorders. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 29 25502632
2019 KLF11 variant in a family clinically diagnosed with early childhood-onset type 1B diabetes. Pediatric diabetes 26 31124255
2014 Epigenetic regulation of uterine biology by transcription factor KLF11 via posttranslational histone deacetylation of cytochrome p450 metabolic enzymes. Endocrinology 26 25076120
2009 Epigenetic inactivation of tumour suppressor gene KLF11 in myelodysplastic syndromes*. European journal of haematology 25 20002157
2018 KLF11 promotes gastric cancer invasion and migration by increasing Twist1 expression. Neoplasma 24 30509092
2007 Human TIEG2/KLF11 induces oligodendroglial cell death by downregulation of Bcl-XL expression. Journal of neural transmission (Vienna, Austria : 1996) 24 17308981
2019 Radiotherapy in combination with hyperthermia suppresses lung cancer progression via increased NR4A3 and KLF11 expression. International journal of radiation biology 23 31498019
2019 KLF11 (Krüppel-Like Factor 11) Inhibits Arterial Thrombosis via Suppression of Tissue Factor in the Vascular Wall. Arteriosclerosis, thrombosis, and vascular biology 21 30602303
2017 Knockdown of KLF11 attenuates hypoxia/reoxygenation injury via JAK2/STAT3 signaling in H9c2. Apoptosis : an international journal on programmed cell death 21 27848055
2016 TGF-β Induces Endometriotic Progression via a Noncanonical, KLF11-Mediated Mechanism. Endocrinology 21 27384304
2004 Gene structure and evolution of Tieg3, a new member of the Tieg family of proteins. Gene 21 14697507
2014 Involvement of KLF11 in hepatic glucose metabolism in mice via suppressing of PEPCK-C expression. PloS one 20 24586865
2008 The Neuroprotective Effect of Antidepressant Drug via Inhibition of TIEG2-MAO B Mediated Cell Death. Drug discoveries & therapeutics 20 19946577
2013 Krüppel-like transcription factor 11 (KLF11) overexpression inhibits cardiac hypertrophy and fibrosis in mice. Biochemical and biophysical research communications 18 24333413
2007 Functional domains of the TGF-beta-inducible transcription factor Tieg3 and detection of two putative nuclear localization signals within the zinc finger DNA-binding domain. Journal of cellular biochemistry 18 17252542
2010 Ethanol increases TIEG2-MAO B cell death cascade in the prefrontal cortex of ethanol-preferring rats. Neurotoxicity research 17 20204567
2021 KLF11 Protects against Venous Thrombosis via Suppressing Tissue Factor Expression. Thrombosis and haemostasis 16 34428834
2020 KLF11 protects chondrocytes via inhibiting p38 MAPK signaling pathway. European review for medical and pharmacological sciences 16 32633337
2013 The expression of KLF11 (TIEG2), a monoamine oxidase B transcriptional activator in the prefrontal cortex of human alcohol dependence. Alcoholism, clinical and experimental research 16 23915421
2015 Promoter DNA methylation is associated with KLF11 expression in epithelial ovarian cancer. Genes, chromosomes & cancer 15 25931269
2025 Wogonin Attenuates Atherosclerosis via KLF11-Mediated Suppression of PPARα-YAP1-Driven Glycolysis and Enhancement of ABCA1/G1-Mediated Cholesterol Efflux. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 14 40397286
2024 CGRP causes anxiety via HP1γ-KLF11-MAOB pathway and dopamine in the dorsal hippocampus. Communications biology 13 38503899
2006 The Krüppel-like factor 11 (KLF11) Q62R polymorphism is not associated with type 2 diabetes in 8,676 people. Diabetes 13 17130512
2022 KLF11 deficiency enhances chemokine generation and fibrosis in murine unilateral ureteral obstruction. PloS one 12 35413089
2019 Induction of airway progenitor cells via p63 and KLF11 by Rho-kinase inhibitor Y27632 in hTERT-human nasal epithelial cells. American journal of translational research 12 30899365
2015 Phenotypic Characterization of Mice Carrying Homozygous Deletion of KLF11, a Gene in Which Mutations Cause Human Neonatal and MODY VII Diabetes. Endocrinology 12 26248217
2024 Ferroptosis inhibitor alleviates sorafenib-induced cardiotoxicity by attenuating KLF11-mediated FSP1-dependent ferroptosis. International journal of biological sciences 11 38725840
2021 Clinical and Functional Characteristics of a Novel KLF11 Cys354Phe Variant Involved in Maturity-Onset Diabetes of the Young. Journal of diabetes research 11 33604390
2017 Progressive Fibrosis: A Progesterone- and KLF11-Mediated Sexually Dimorphic Female Response. Endocrinology 10 28938437
2015 Chronic Social Stress and Ethanol Increase Expression of KLF11, a Cell Death Mediator, in Rat Brain. Neurotoxicity research 10 25739536
2013 KLF11 epigenetically regulates glycodelin-A, a marker of endometrial biology via histone-modifying chromatin mechanisms. Reproductive sciences (Thousand Oaks, Calif.) 10 24060634
2023 The induction of ferroptosis by KLF11/NCOA4 axis: the inhibitory role in clear cell renal cell carcinoma. Human cell 9 37642832
2024 SKP2-mediated ubiquitination and degradation of KLF11 promotes osteoarthritis via modulation of JMJD3/NOTCH1 pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 8 38690715
2017 KLF11 is an Epigenetic Mediator of DRD2/Dopaminergic Signaling in Endometriosis. Reproductive sciences (Thousand Oaks, Calif.) 8 28372535
2005 Transcriptional regulation of FKLF-2 (KLF13) gene in erythroid cells. Biochimica et biophysica acta 8 15716005
2024 Maturity-onset Diabetes of the Young Type 7 (MODY7) and the Krüppellike Factor 11 Mutation (KLF11). A Review. Current diabetes reviews 7 36944622
2022 Genetic and Functional Analyses of the Novel KLF11 Pro193Thr Variant in a Three-Generation Family with MODY7. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 7 36241199
2015 All trans retinoic acid (ATRA) mediated modulation of N-methyl D-aspartate receptor (NMDAR) and Kruppel like factor 11 (KLF11) expressions in the mitigation of ethanol induced alterations in the brain. Neurochemistry international 7 25754253
2024 Endothelial KLF11 is a novel protector against diabetic atherosclerosis. Cardiovascular diabetology 6 39462409
2022 MiR-128-1-5p regulates differentiation of ovine stromal vascular fraction by targeting the KLF11 5'-UTR. Domestic animal endocrinology 6 35338828
2022 A novel KLF11 variant in a family with maturity-onset diabetes of the young. Pediatric diabetes 6 35689450
2024 Aberrant cell adhesiveness due to DNA hypermethylation of KLF11 in papillary urothelial carcinomas. Experimental and molecular pathology 5 38824688
2022 KLF11 promotes the progression of glioma via regulating Holliday junction recognition protein. Cell biology international 4 35293659
2020 DNA hypomethylation of the Krüppel-like factor 11 (KLF11) gene promoter: a putative biomarker of depression comorbidity in panic disorder and of non-anxious depression? Journal of neural transmission (Vienna, Austria : 1996) 4 32524199
2024 KLF11 promotes the proliferation of breast cancer cells by inhibiting p53-MDM2 signaling. Cellular signalling 3 38810862
2024 miR-10a-5p Regulates the Proliferation and Differentiation of Porcine Preadipocytes Targeting the KLF11 Gene. Animals : an open access journal from MDPI 2 38275797
2024 Effects of KLF11 on Vascular Smooth Muscle Cells and its Underlying Mechanisms in Intracranial Aneurysm. Biochemical genetics 2 38368567
2024 [Upregulating KLF11 ameliorates intestinal inflammation in mice with 2, 4, 6-trinitrobenesulfonic acid-induced colitis by inhibiting the JAK2/STAT3 signaling pathway]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 2 38708511
2024 A Novel KLF11 c.793G>A (p.Glu265Lys) Variant Identified in a Chinese Family with Controversial Association with MODY7. Clinical laboratory 2 39193968
2023 KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11. Open medicine (Warsaw, Poland) 2 38025523
2026 KLF11 interacts with MDM2 to stabilize E2F1 and promotes DNA damage repair to induce radioresistance in esophageal cancer cells. Pathology, research and practice 1 41655531
2025 KLF11/TMEM87B promoted the occurrence of glioma and decreased TMZ sensitivity. Cellular signalling 1 39929351
2025 KLF11 alleviates rheumatoid arthritis by regulating M1 macrophage polarization via downregulation of YAP1 expression. Arthritis research & therapy 1 40859359
2010 Dynamic transcriptional changes of TIEG1 and TIEG2 during mouse tissue development. Anatomical record (Hoboken, N.J. : 2007) 1 20201061
2026 FXR-mediated transcriptional regulation of KLF11 mitigates contrast-induced acute kidney injury via suppressing JAK2/STAT3 pathway. International immunopharmacology 0 41855776
2026 Clinical and functional characteristics of the KLF11 (p.R29Q) variant associated with MODY7. Frontiers in endocrinology 0 41890190
2025 Rare BLK, CEL, KLF11, PDX1, and PAX4 Gene Variants in Russian Patients with Monogenic Diabetes: Clinical and Molecular Characterization. Biomedicines 0 41153735
2025 piR-hsa-022095 Drives Hypertrophic Scar Formation via KLF11-Dependent Fibroblast Proliferation. Biomedicines 0 41462975

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