Affinage

KLF6

Krueppel-like factor 6 · UniProt Q99612

Length
283 aa
Mass
31.9 kDa
Annotated
2026-06-10
100 papers in source corpus 38 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KLF6 is a C2H2 Krüppel-type zinc-finger transcription factor that binds GC-box and CACCC promoter motifs to activate or repress target genes, functioning as a tumor suppressor and as a regulator of tissue-specific differentiation, fibrogenesis, and inflammation (PMID:9685731, PMID:11752579, PMID:9837963). Its growth-suppressive program operates through p53-independent transactivation of p21(WAF1/CIP1) and physical disruption of cyclin D1–CDK4 complexes, which redistributes p21 onto CDK2, reduces Rb phosphorylation, and enforces G1 arrest (PMID:11752579, PMID:15172998); this anti-proliferative output is augmented by direct GSK3β phosphorylation at a consensus site, and tumor-derived mutants that abolish either p21 induction or this phosphosite lose suppressor activity (PMID:23085750). KLF6 also drives apoptosis by directly binding and activating the ATF3 promoter (PMID:18755691), and restrains pro-metastatic programs by repressing E2F1-driven EMT (PMID:27780824), the VAV3–RAC1 GTPase axis (PMID:26876204), and basigin-2 (PMID:27057625). A cytoplasmic dominant-negative splice variant, KLF6-SV1, opposes these functions: it promotes proliferation, invasion, and tumor growth in vivo and binds the proapoptotic protein NOXA to trigger HDM2-dependent degradation of both, elevating Mcl-1 and blocking apoptosis (PMID:15994951, PMID:19435908). Beyond cancer, KLF6 binds the TGF-β1 promoter and the TGF-β type I/II receptor and uPA promoters to establish an autocrine fibrogenic loop in activated hepatic stellate and endothelial cells (PMID:9837963, PMID:10666204), cooperates with Sp1 and a bridged Smad3 complex in TGF-β signaling (PMID:19076057), promotes pro-inflammatory macrophage programs by enhancing NF-κB and repressing STAT3 signaling (PMID:26838049), and maintains mature β-cell identity and proliferation (PMID:32244185). KLF6 nuclear retention depends on an NLS within the zinc-finger domain whose disruption destabilizes the protein and abolishes target transactivation (PMID:20844588).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1998 Medium

    Established KLF6 as a GC-rich-binding zinc-finger transcription factor, defining its molecular identity and DNA-binding architecture.

    Evidence Yeast one-hybrid screening, cDNA cloning, and in vitro DNA binding against the HIV-1 core promoter

    PMID:9685731

    Open questions at the time
    • No physiological target genes identified at this stage
    • No structural model of DNA contacts
  2. 1998 High

    Linked KLF6 to fibrogenic signaling by showing it binds and transactivates the TGF-β1 ligand and receptor promoters, suggesting an autocrine loop.

    Evidence EMSA with recombinant Zf9-GST, reporter assays in hepatic stellate cells and multiple cell lines, plus nuclear/perinuclear localization in activated stellate cells

    PMID:9689109 PMID:9837963

    Open questions at the time
    • Cell-context dependence of collagen promoter activation unresolved
    • In vivo fibrosis contribution not tested
  3. 2000 High

    Extended the fibrogenic loop to extracellular proteolysis by demonstrating KLF6 transactivates uPA, which activates latent TGF-β.

    Evidence Recombinant protein EMSA with mutational controls, reporter assays, endogenous mRNA/activity measurement in endothelial cells

    PMID:10666204

    Open questions at the time
    • Direct in vivo evidence for the uPA–TGF-β feedback absent
  4. 2001 High

    Defined KLF6 as a tumor suppressor by showing p53-independent p21 induction is lost in tumor-derived mutants, providing the founding growth-suppressive mechanism.

    Evidence Functional transfection, proliferation assays, loss-of-function with tumor-derived mutants

    PMID:11752579

    Open questions at the time
    • Mechanism of p21 promoter engagement not detailed
    • Did not address cyclin/CDK level effects
  5. 2004 High

    Resolved how KLF6 enforces G1 arrest, showing it disrupts cyclin D1–CDK4 complexes and redistributes p21 onto CDK2 to lower Rb phosphorylation.

    Evidence Reciprocal co-IP, cell cycle analysis, Rb phosphorylation assays in cancer cell lines

    PMID:15172998

    Open questions at the time
    • Structural basis of cyclin D1 binding unknown
    • Whether transcriptional and direct-binding arms are independent unresolved
  6. 2005 High

    Identified KLF6-SV1 as a dominant-negative cytoplasmic isoform that antagonizes wild-type tumor suppression in vitro and in vivo.

    Evidence siRNA knockdown, colony formation, invasion assays, xenograft mouse model

    PMID:15994951

    Open questions at the time
    • Molecular basis of SV1 antagonism not yet defined at this step
  7. 2008 High

    Defined a transcriptional apoptosis pathway, showing KLF6 directly activates ATF3 to drive cell death, and tumor mutants fail to do so.

    Evidence ChIP, promoter reporter, siRNA epistasis, mutant analysis, apoptosis assays in prostate cancer cells

    PMID:18755691

    Open questions at the time
    • Downstream ATF3 effectors not mapped
    • Stress signals upstream of KLF6 induction unclear
  8. 2009 High

    Elucidated the SV1 antiapoptotic mechanism, showing it binds NOXA to promote mutual HDM2-dependent degradation and stabilize Mcl-1.

    Evidence Co-IP, siRNA knockdown, apoptosis assays, xenograft model

    PMID:19435908

    Open questions at the time
    • Stoichiometry and direct HDM2 contacts not defined
  9. 2009 Medium

    Showed KLF6 cooperates with Sp1 and integrates TGF-β signaling via an Sp1-bridged Smad3 complex.

    Evidence Co-transfection, co-IP, FRET

    PMID:19076057

    Open questions at the time
    • Indirect (Sp1-bridged) Smad3 interaction shown by FRET only
    • Genome-wide cooperative targets not mapped
  10. 2012 High

    Identified GSK3β phosphorylation as a positive regulator that augments KLF6-mediated p21 transactivation and growth suppression.

    Evidence In vitro/in vivo kinase assays, reciprocal co-IP, phosphomutant, reporter and growth assays

    PMID:23085750

    Open questions at the time
    • Upstream signals controlling GSK3β–KLF6 axis unclear
    • Interaction with S6K1 phosphorylation untested
  11. 2010 Medium

    Mapped the trafficking determinants, locating an NLS in the zinc-finger domain whose disruption destabilizes KLF6 and abolishes target transactivation.

    Evidence EGFP-fusion live imaging, site-directed mutagenesis, Crm1 inhibition, reporter assays

    PMID:20844588

    Open questions at the time
    • Export adaptor for Crm1-dependent shuttling not identified
    • Single lab
  12. 2016 High

    Defined the anti-metastatic transcriptional repertoire, showing KLF6 represses E2F1-driven EMT, the VAV3–RAC1 axis, and basigin-2.

    Evidence ChIP-seq, gene expression profiling, RAC1 activity and double-knockdown epistasis, mouse tumor/metastasis models

    PMID:26876204 PMID:27057625 PMID:27780824

    Open questions at the time
    • Whether these axes are co-regulated or context-specific is unresolved
    • Direct repressor cofactors not fully defined
  13. 2020 High

    Extended KLF6 to immune and endocrine biology, showing it drives pro-inflammatory macrophage programs and maintains mature β-cell identity.

    Evidence Conditional knockout mice (myeloid- and β-cell-specific), gain/loss-of-function, DSS colitis and insulin-resistance models, transcriptomics

    PMID:26838049 PMID:32244185

    Open questions at the time
    • Direct transcriptional targets in macrophages and β-cells incompletely mapped
    • Tissue-specific cofactor requirements unclear
  14. 2024 Medium

    Revealed cell-non-autonomous signaling, showing podocyte KLF6 induces ApoJ secretion that activates CaMK1D in adjacent proximal tubule cells.

    Evidence Podocyte-specific transgenic mouse, snRNA-seq, snATAC-seq, mass spectrometry, diabetic kidney disease model

    PMID:39271683

    Open questions at the time
    • Direct KLF6 target driving ApoJ secretion not defined
    • Single model system

Open questions

Synthesis pass · forward-looking unresolved questions
  • How KLF6's bidirectional activity (activator vs repressor) and isoform balance (full-length vs SV1) are switched across tissues and disease contexts remains unresolved.
  • No unified model of cofactor-dependent activator/repressor switching
  • Mechanism controlling KLF6 alternative splicing to SV1 in vivo unclear
  • No structural model of KLF6–DNA or KLF6–partner complexes

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 6 GO:0140110 transcription regulator activity 6
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-168256 Immune System 2
Partners
CCND1KLF4NOXASMAD3SP1SP2SRCTP53
Complex memberships
KLF6-SP2 MMP-9 repressor complexKLF6-Sp1-Smad3 transcriptional complex

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Wild-type KLF6 up-regulates p21 (WAF1/CIP1) in a p53-independent manner and significantly reduces cell proliferation; tumor-derived KLF6 mutants lose this activity, establishing KLF6 as a tumor suppressor acting through p21 induction. Functional transfection assays, cell proliferation assays, loss-of-function with tumor-derived mutants Science High 11752579
1998 KLF6 (Zf9/COPEB) binds GC-box motifs in the TGF-β1 promoter and the TGF-β type I and II receptor promoters via recombinant Zf9-GST, and transactivates these promoters in hepatic stellate cells and other mammalian cell lines, suggesting an autocrine fibrogenic loop. EMSA (gel shift), recombinant protein-DNA binding, transient transfection reporter assays in multiple cell lines including Drosophila S2 cells The Journal of biological chemistry High 9837963
1998 KLF6 (Zf9) is localized to the nucleus and perinuclear zone in activated hepatic stellate cells but not quiescent cells; its N-terminal domain (aa 1–201) is transactivating; it binds GC-box DNA sequences and transactivates a collagen α1(I) promoter reporter in a cell-context-dependent manner. Nuclear fractionation/localization, GAL4-hybrid transactivation assay, EMSA, transient transfection reporter assays Proceedings of the National Academy of Sciences of the United States of America High 9689109
2000 KLF6 (Zf9/COPEB) transcriptionally activates the urokinase plasminogen activator (uPA) gene by binding GC-box motifs in the uPA promoter, resulting in increased endogenous uPA mRNA and activity in vascular endothelial cells, which in turn activates latent TGF-β. Recombinant Zf9-GST pulldown/EMSA with mutant and wild-type GC-box promoter elements, transient transfection reporter assays, endogenous mRNA/activity measurement Blood High 10666204
2000 KLF6 (Zf9) physically interacts with GKLF/KLF4 and together they co-activate the human keratin 4 promoter in an additive manner in esophageal cancer cell lines; this is the first reported physical interaction between two Krüppel-like family members. Co-immunoprecipitation (physical interaction), transient co-transfection reporter assays FEBS letters Medium 10802067
2004 KLF6 mediates growth inhibition by physically interacting with cyclin D1, disrupting cyclin D1–CDK4 complexes, forcing redistribution of p21(Cip/Kip) onto CDK2, and reducing Rb phosphorylation at Ser795, leading to G1 arrest. Co-immunoprecipitation, cell cycle analysis, Rb phosphorylation assays, over-expression in cancer cell lines Cancer research High 15172998
2005 KLF6-SV1 (a cytoplasmic splice isoform) functionally antagonizes wild-type KLF6 tumor suppressor activity: SV1 increases cell proliferation, colony formation, and invasion, while siRNA-mediated SV1 knockdown reduces tumor growth (~50%) in nude mice and decreases growth/angiogenesis-related proteins. siRNA knockdown, colony formation assay, invasion assay, xenograft mouse model Cancer research High 15994951
2004 KLF6 transactivates the IGF-I receptor (IGF-IR) promoter through a cluster of four GC boxes (−399 to −331) in a Sp1-dependent manner (no activity in Sp1-null Drosophila cells); KLF6 physically interacts with p53 and shows enhanced activity in p53-containing cells. Transient co-transfection reporter assays, promoter deletion analysis, co-immunoprecipitation (KLF6–p53 interaction) Endocrinology Medium 15131018
2006 KLF6 and SP2 form a repressor complex on the MMP-9 promoter to maintain silenced expression; upon FXR activation, SHP interacts with SP2 and KLF6 to disrupt this repressor complex, de-repressing MMP-9 and promoting endothelial cell motility. siRNA silencing, chromatin immunoprecipitation (ChIP), EMSA gel shift, promoter reporter assays, co-immunoprecipitation The Journal of biological chemistry High 17071613
2008 KLF6 induces apoptosis in prostate cancer cells by directly binding to and activating the ATF3 promoter; ATF3 then mediates apoptosis downstream. Cancer-derived KLF6 mutants fail to activate ATF3 and cannot induce apoptosis. KLF6 knockdown blocks stress-induced ATF3 upregulation and apoptosis. Chromatin immunoprecipitation, promoter reporter assay, siRNA knockdown, ectopic expression, apoptosis assays The Journal of biological chemistry High 18755691
2009 KLF6 co-operates with Sp1 to regulate KLF6-responsive genes, and this co-operation is enhanced by TGF-β1 through: (1) decreased alternative splicing of KLF6 in specific cell types; (2) formation of a tripartite KLF6–Sp1–Smad3 complex, where KLF6 interacts indirectly with Smad3 through Sp1 as a bridging molecule. Co-transfection assays, co-immunoprecipitation, FRET (fluorescence resonance energy transfer) The Biochemical journal Medium 19076057
2009 KLF6-SV1 binds the proapoptotic BH3-only protein NOXA, resulting in their mutual HDM2-dependent proteasomal degradation, which increases intracellular Mcl-1 levels and blocks apoptosis; this mechanism confers a prosurvival/antiapoptotic function to KLF6-SV1. Co-immunoprecipitation (KLF6-SV1–NOXA interaction), siRNA knockdown, apoptosis assays, in vivo xenograft model Cancer research High 19435908
2006 KLF6 phosphorylation by p70 ribosomal S6 kinase 1 (S6K1) at serine residues promotes TGF-β1 gene transactivation; PPARγ–RXR activation via PTEN-mediated S6K1 inhibition leads to Zf9 dephosphorylation and repression of the TGF-β1 gene. 32P phosphorylation assay, constitutively active/dominant negative S6K1 transfection, promoter deletion/reporter assay Molecular pharmacology Medium 16611854
2010 KLF6 nuclear export is Crm1-dependent; a novel nuclear localization signal (NLS) resides within the zinc finger (ZF) domain, while a nuclear export signal (NES) is in the first 16 amino acids of the shared N-terminus. Disruption of the NLS by site-directed mutagenesis impairs KLF6 protein stability and abolishes transactivation of E-cadherin and p21. Addition of the ZF domain to KLF6-SV1 redirects it to the nucleus and decreases its half-life. EGFP fusion constructs and live-cell imaging, site-directed mutagenesis, Crm1 inhibition, RT-PCR and luciferase reporter assays for target genes PloS one Medium 20844588
2012 GSK3β directly phosphorylates KLF6 at a consensus phosphorylation site; this phosphorylation augments KLF6-mediated p21 transactivation and growth suppression. Cancer-derived KLF6 mutants that disrupt this GSK3β site (KLF6-4A phosphomutant) lose GSK3β-augmented tumor suppressor activity. In vitro and in vivo 32P incorporation kinase assays, reciprocal co-immunoprecipitation, site-directed mutagenesis, p21 promoter reporter assays, cell growth assays Oncogene High 23085750
2012 KLF6 is a key transcriptional target of MEF2D in embryonic hippocampal neurons; siRNA knockdown of KLF6 promotes neuronal cell death and antagonizes the prosurvival role of MEF2D. PKA signaling represses MEF2D transactivation and thereby suppresses this KLF6-dependent survival pathway. siRNA knockdown, luciferase reporter gene assays, TUNEL/FACS apoptosis analysis, MEF2D phosphomutant rescue experiments The Journal of neuroscience Medium 22357862
2002 KLF6 (KLF-6/Zf9) binds the BS5-B element (containing a CACCC motif) in the first intron of the HSP47 gene and activates its expression; this was confirmed by chromatin immunoprecipitation showing endogenous KLF6 occupies this element in vivo. Yeast one-hybrid screen, ChIP assay, luciferase reporter transfection The Journal of biological chemistry Medium 12235161
2010 Klf6 is required for hepatic outgrowth in zebrafish (copeb morpholino knockdown blocks liver, pancreas, and intestine expansion but not specification) and for hepatocyte specification from mouse ES cells. Decreased hepatocyte proliferation in copeb morphants is accompanied by upregulation of the cell cycle inhibitor cdkn1a (a KLF6 transcriptional target). Morpholino knockdown in zebrafish, Klf6 KO mouse ES cell differentiation, gene expression analysis Developmental biology Medium 20430021
2006 KLF6 protein is rapidly degraded via ubiquitin-proteasome pathway upon induction of apoptosis through the intrinsic pathway (by cisplatin, adriamycin, or UVB), with a half-life of ~16 min; degradation is caspase- and calpain-independent and p53-independent. Apoptosis via the extrinsic/death-receptor pathway does not affect KLF6 levels. Western blot of KLF6 protein levels under various apoptotic stimuli, proteasome inhibitor rescue, ubiquitination detection, multiple cell lines FEBS letters Medium 17113081
2016 KLF6 transcriptionally represses E2F1 in clear cell renal cell carcinoma; KLF6 silencing promotes E2F1-mediated epithelial-mesenchymal transition and metastasis, while E2F1 silencing reverses the pro-metastatic effects of KLF6 knockdown. Genetic knockdown/overexpression, xenograft mouse model with metastasis readout, epistasis (KLF6 KD + E2F1 KD rescue) Cancer research Medium 27780824
2016 KLF6 transcriptionally activates MMP14 (MT1-MMP) expression in vascular endothelial cells; KLF6 directly interacts with the MMP14 promoter (confirmed by ChIP), and this interaction increases during wound healing. Klf6+/− mice show lower MMP14 levels after wire-induced denudation. Increased MMP14 leads to proteolytic release of soluble endoglin. ChIP assay, promoter reporter assays, ectopic expression/knockdown, Klf6+/- mouse model, in vitro wound healing Angiogenesis High 26850053
2015 Elevated H3K9me3 at KLF6 regulatory regions represses KLF6 expression in dedifferentiated liposarcoma (DDLPS); pharmacologic inhibition of H3K9me3 restores KLF6 expression and induces adipogenic differentiation markers; KLF6 overexpression partially phenocopies this effect, suggesting H3K9me3 mediates DDLPS dedifferentiation through KLF6 repression. ChIP-seq (H3K9me3 profiling), gene expression analysis, pharmacologic inhibition (chaetocin), KLF6 overexpression with phenotypic readout The Journal of clinical investigation Medium 26193637
2016 KLF6 depletion in glioblastoma promotes NF-κB nuclear localization and activates NF-κB target genes; KLF6 reconstitution transactivates multiple negative regulators of the NF-κB pathway, attenuates malignant phenotype, and induces neural-like differentiation and senescence. KLF6 reconstitution in GBM cell lines, NF-κB reporter and target gene analysis, LOH analysis of patient tumors Oncogene Medium 28166199
2016 KLF6 suppresses HCC cell migration by transcriptionally repressing VAV3, a RAC1 GTPase activator; KLF6 knockdown increases RAC1 activity in a VAV3-dependent manner. This KLF6–VAV3–RAC1 axis was identified by combining gene expression profiling and ChIP-seq. ChIP-seq, gene expression profiling, RAC1 activity assays, siRNA epistasis (VAV3/RAC1 knockdown rescues KLF6 KD phenotype), mouse HCC model Oncogene High 26876204
2019 In clear cell renal cell carcinoma, KLF6 supports a transcriptional network that sustains lipid homeostasis genes and promotes PDGFB expression, which activates mTOR signaling and downstream lipid metabolism regulators SREBF1/SREBF2. KLF6 expression is driven by a super enhancer integrating signals from the ccRCC-initiating VHL-HIF2A pathway. Transcriptional network analysis, reporter assays, ChIP/super enhancer mapping, genetic knockdown with lipid metabolism and mTOR pathway readouts Nature communications Medium 30858363
2020 KLF6 promotes pro-inflammatory gene expression in macrophages by enhancing NF-κB signaling while suppressing anti-inflammatory genes via STAT3 pathway repression; myeloid-specific KLF6 knockout mice are protected against DSS-induced colitis. Conditional knockout mice (Mac-KLF6-KO), gain/loss-of-function studies, DSS colitis model, gene expression analysis Mucosal immunology High 26838049
2018 KLF6 and STAT3 co-occupy regulatory DNA elements genome-wide (confirmed by ATAC-seq footprinting); co-expression of KLF6 and STAT3 yields synergistic elevation of neurite growth in vitro; forced KLF6 expression promotes corticospinal tract axon regeneration in the injured spinal cord. RNA-seq (gene expression after KLF6 OE), ATAC-seq genome-wide footprinting, co-expression/synergy neurite assay, in vivo spinal cord injury model Scientific reports Medium 30135567
2020 Klf6 β-cell-specific knockout blunts β-cell proliferation induced by insulin resistance (pregnancy, HFD, insulin receptor antagonism) and causes dedifferentiation: loss of mature β-cell identity gene expression, induction of disallowed genes impairing insulin secretion, and increased β-to-α cell transdifferentiation. β-cell-specific conditional Klf6 KO mouse model, transcriptomic analysis, multiple physiological insulin resistance models Molecular metabolism High 32244185
2009 KLF6 inhibits ERα-mediated breast cancer cell growth through physical interaction with c-Src, which inactivates Erk and Akt signaling; this effect is specific to ERα-positive cells. Co-immunoprecipitation (KLF6–c-Src interaction), MTT cell proliferation assay, Western blot for Erk/Akt phosphorylation Molecular and cellular biochemistry Medium 19707857
2023 KLF6 inhibits overactivation of autophagy during hepatic ischemia-reperfusion injury by directly binding the Beclin1 promoter (confirmed by ChIP-qPCR and luciferase assay) to suppress its transcription, and by activating the mTOR/ULK1 pathway. ChIP-qPCR, luciferase reporter assay, adenoviral KO/OE in mice, hypoxia-reoxygenation cell model, autophagy markers Cell death & disease Medium 37391422
2022 KLF6 inhibits miR-223-3p by directly binding to the miR-223-3p promoter (confirmed by ChIP), thereby promoting NLRP3 expression and activating the NLRP3/Caspase-1/IL-1β pyroptosis pathway in renal tubular epithelial cells during septic acute kidney injury. ChIP assay, dual-luciferase reporter assay, siRNA knockdown, in vivo sepsis model, rescue experiment Shock Medium 34710881
2020 CBX4 physically binds HDAC1 to maintain HDAC1 localization on the KLF6 promoter, thereby transcriptionally suppressing KLF6 expression in ccRCC; ectopic KLF6 or disruption of CBX4–HDAC1 interaction attenuates CBX4-mediated cell growth and migration. Co-immunoprecipitation (CBX4–HDAC1), ChIP (HDAC1 on KLF6 promoter), promoter reporter assay, functional rescue with KLF6 OE EBioMedicine Medium 32113161
2023 m6A methylation-regulated Klf6 aggravates myocardial ischemia/reperfusion injury through Acsl4-mediated ferroptosis; Klf6 directly binds the Acsl4 promoter (confirmed by ChIP and luciferase assay) and positively regulates its expression; Klf6 mRNA stability is maintained by Igf2bp2 binding. MeRIP (m6A profiling), ChIP, luciferase reporter assay, RNA immunoprecipitation, RNA pull-down, siRNA knockdown, I/R mouse model The Kaohsiung journal of medical sciences Medium 37530646
2008 KLF6 silencing in HCC-derived cells causes G1-phase arrest, inhibits CDK4 and cyclin D1 expression, reduces Rb phosphorylation, upregulates p53, and inhibits Bcl-xL to induce apoptosis, demonstrating that KLF6 is required by HCC cells to evade apoptosis. RNA interference (siRNA), cell cycle analysis, Western blot for CDK4/cyclin D1/Rb phosphorylation/p53/Bcl-xL Cell death and differentiation Medium 17347668
1998 KLF6 (GBF) is a novel zinc-finger transcription factor that binds GC-rich sequences in the HIV-1 core promoter, isolated by yeast one-hybrid screening; primary structure reveals C2H2 Krüppel-type zinc fingers with acidic and proline-rich N-terminal domains. Yeast one-hybrid screening, cDNA cloning, in vitro DNA binding Journal of biochemistry Medium 9685731
2016 KLF6 binds the basigin-2 (BSG2) and Sp1 promoters and represses their expression; KLF6 can suppress HCC invasion/metastasis both directly (binding basigin-2 promoter) and indirectly (repressing Sp1 to block BSG2). ChIP (KLF6 on BSG2 and Sp1 promoters), promoter reporter assay, overexpression/knockdown with in vitro invasion/metastasis readout and in vivo xenograft Oncotarget Medium 27057625
2005 KLF6 promoter transcription is initiated at an Initiator element (no TATA-box); Sp1 ectopic expression increases KLF6 promoter transcriptional activity, and two strong activating sequences (−407/−344 and −307/−207) containing Sp1/CAAT-box sites were identified. Promoter deletion analysis, transfection reporter assays, transcription start site mapping, Sp1 co-transfection Biochimica et biophysica acta Medium 16054710
2024 Podocyte-specific KLF6 induction triggers secretion of ApoJ (clusterin) which activates CaMK1D signaling in neighboring proximal tubule (PT) cells; CaMK1D is enriched in the first PT segment proximal to podocytes and attenuates mitochondrial fission under diabetic conditions. Podocyte-specific transgenic mouse model, snRNA-seq, snATAC-seq, tandem mass spectrometry, in vivo DKD model Nature communications Medium 39271683

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 KLF6, a candidate tumor suppressor gene mutated in prostate cancer. Science (New York, N.Y.) 386 11752579
1995 The G-box: a ubiquitous regulatory DNA element in plants bound by the GBF family of bZIP proteins. Trends in biochemical sciences 290 8571452
1998 Transcriptional activation of transforming growth factor beta1 and its receptors by the Kruppel-like factor Zf9/core promoter-binding protein and Sp1. Potential mechanisms for autocrine fibrogenesis in response to injury. The Journal of biological chemistry 227 9837963
1998 Zf9, a Kruppel-like transcription factor up-regulated in vivo during early hepatic fibrosis. Proceedings of the National Academy of Sciences of the United States of America 215 9689109
2005 Targeted inhibition of the KLF6 splice variant, KLF6 SV1, suppresses prostate cancer cell growth and spread. Cancer research 137 15994951
2004 Cyclin-dependent kinase inhibition by the KLF6 tumor suppressor protein through interaction with cyclin D1. Cancer research 131 15172998
2008 The role of KLF6 and its splice variants in cancer therapy. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 120 19097929
2003 Deletion, mutation, and loss of expression of KLF6 in human prostate cancer. The American journal of pathology 118 12651626
2022 Mesenchymal stem cell-derived exosomes protect against liver fibrosis via delivering miR-148a to target KLF6/STAT3 pathway in macrophages. Stem cell research & therapy 117 35858897
2008 KLF6 induces apoptosis in prostate cancer cells through up-regulation of ATF3. The Journal of biological chemistry 114 18755691
2020 lncRNA-Xist/miR-101-3p/KLF6/C/EBPα axis promotes TAM polarization to regulate cancer cell proliferation and migration. Molecular therapy. Nucleic acids 112 33510942
2000 Transcriptional activation of urokinase by the Krüppel-like factor Zf9/COPEB activates latent TGF-beta1 in vascular endothelial cells. Blood 103 10666204
2006 Roles of KLF6 and KLF6-SV1 in ovarian cancer progression and intraperitoneal dissemination. Clinical cancer research : an official journal of the American Association for Cancer Research 100 16778100
2008 KLF6-SV1 overexpression accelerates human and mouse prostate cancer progression and metastasis. The Journal of clinical investigation 95 18596922
2006 Downregulation of KLF6 is an early event in hepatocarcinogenesis, and stimulates proliferation while reducing differentiation. Journal of hepatology 78 17196295
2019 A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma. Nature communications 77 30858363
2020 Two Sides of the Same Coin: The Roles of KLF6 in Physiology and Pathophysiology. Biomolecules 74 32998281
2006 Disruption of an SP2/KLF6 repression complex by SHP is required for farnesoid X receptor-induced endothelial cell migration. The Journal of biological chemistry 68 17071613
2007 Functional inactivation of the KLF6 tumor suppressor gene by loss of heterozygosity and increased alternative splicing in glioblastoma. International journal of cancer 67 17514651
2016 KLF6 Suppresses Metastasis of Clear Cell Renal Cell Carcinoma via Transcriptional Repression of E2F1. Cancer research 66 27780824
1993 Muscle-specific expression of the acetylcholine receptor alpha-subunit gene requires both positive and negative interactions between myogenic factors, Sp1 and GBF factors. The EMBO journal 62 8382608
2021 RNA-Seq reveals the potential molecular mechanisms of bovine KLF6 gene in the regulation of adipogenesis. International journal of biological macromolecules 59 34890637
2016 Transcription factor KLF6 upregulates expression of metalloprotease MMP14 and subsequent release of soluble endoglin during vascular injury. Angiogenesis 57 26850053
2006 Peroxisome proliferator-activated receptor-gamma and retinoic acid X receptor alpha represses the TGFbeta1 gene via PTEN-mediated p70 ribosomal S6 kinase-1 inhibition: role for Zf9 dephosphorylation. Molecular pharmacology 57 16611854
2007 KLF6 transcription factor protects hepatocellular carcinoma-derived cells from apoptosis. Cell death and differentiation 56 17347668
2000 The Krüppel-like transcriptional factors Zf9 and GKLF coactivate the human keratin 4 promoter and physically interact. FEBS letters 56 10802067
2008 Functional role of the KLF6 tumour suppressor gene in gastric cancer. European journal of cancer (Oxford, England : 1990) 53 19101139
2016 KLF6 contributes to myeloid cell plasticity in the pathogenesis of intestinal inflammation. Mucosal immunology 52 26838049
2004 Transcriptional activation of the insulin-like growth factor I receptor gene by the Kruppel-like factor 6 (KLF6) tumor suppressor protein: potential interactions between KLF6 and p53. Endocrinology 49 15131018
2020 CBX4 transcriptionally suppresses KLF6 via interaction with HDAC1 to exert oncogenic activities in clear cell renal cell carcinoma. EBioMedicine 46 32113161
2009 TGF-beta regulates the expression of transcription factor KLF6 and its splice variants and promotes co-operative transactivation of common target genes through a Smad3-Sp1-KLF6 interaction. The Biochemical journal 43 19076057
2019 MicroRNA-191 promotes hepatocellular carcinoma cell proliferation by has_circ_0000204/miR-191/KLF6 axis. Cell proliferation 42 31334580
2012 Suppression of a MEF2-KLF6 survival pathway by PKA signaling promotes apoptosis in embryonic hippocampal neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 42 22357862
2018 KLF6 and STAT3 co-occupy regulatory DNA and functionally synergize to promote axon growth in CNS neurons. Scientific reports 41 30135567
2008 KLF6 and TP53 mutations are a rare event in prostate cancer: distinguishing between Taq polymerase artifacts and true mutations. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 41 19020536
2014 Identification of miRNAs that specifically target tumor suppressive KLF6-FL rather than oncogenic KLF6-SV1 isoform. RNA biology 40 24921656
2003 Genetic susceptibility to dupuytren disease: association of Zf9 transcription factor gene. Plastic and reconstructive surgery 40 12794452
2019 miR-148a-3p regulates proliferation and apoptosis of bovine muscle cells by targeting KLF6. Journal of cellular physiology 39 30793769
2020 KLF6 Induces Apoptosis in Human Lens Epithelial Cells Through the ATF4-ATF3-CHOP Axis. Drug design, development and therapy 38 32210535
2009 KLF6-SV1 is a novel antiapoptotic protein that targets the BH3-only protein NOXA for degradation and whose inhibition extends survival in an ovarian cancer model. Cancer research 38 19435908
2017 MiR-630 promotes epithelial ovarian cancer proliferation and invasion via targeting KLF6. European review for medical and pharmacological sciences 37 29131262
2012 GSK3β phosphorylation of the KLF6 tumor suppressor promotes its transactivation of p21. Oncogene 37 23085750
1998 Isolation and initial characterization of GBF, a novel DNA-binding zinc finger protein that binds to the GC-rich binding sites of the HIV-1 promoter. Journal of biochemistry 36 9685731
2005 Absence of mutation in the putative tumor-suppressor gene KLF6 in colorectal cancers. Oncogene 35 16044160
2002 [Mutation analysis of KLF6 gene in human nasopharyngeal carcinomas]. Ai zheng = Aizheng = Chinese journal of cancer 35 12508640
2017 KLF6 inhibited oral cancer migration and invasion via downregulation of mesenchymal markers and inhibition of MMP-9 activities. International journal of medical sciences 34 28638268
2015 Increased H3K9me3 drives dedifferentiated phenotype via KLF6 repression in liposarcoma. The Journal of clinical investigation 34 26193637
2010 The SV2 variant of KLF6 is down-regulated in hepatocellular carcinoma and displays anti-proliferative and pro-apoptotic functions. Journal of hepatology 34 20801538
2006 Transcriptional regulation of post-aggregation genes in Dictyostelium by a feed-forward loop involving GBF and LagC. Developmental biology 34 16386729
2023 KLF6 alleviates hepatic ischemia-reperfusion injury by inhibiting autophagy. Cell death & disease 33 37391422
2019 Expression of the bovine KLF6 gene polymorphisms and their association with carcass and body measures in Qinchuan cattle (Bos Taurus). Genomics 32 30880114
2017 KLF6 depletion promotes NF-κB signaling in glioblastoma. Oncogene 32 28166199
2006 Genetic and epigenetic alterations of the KLF6 gene in hepatocellular carcinoma. Journal of gastroenterology and hepatology 32 16872311
2023 MicroRNA-22-3p in human umbilical cord mesenchymal stem cell-secreted exosomes inhibits granulosa cell apoptosis by targeting KLF6 and ATF4-ATF3-CHOP pathway in POF mice. Apoptosis : an international journal on programmed cell death 31 37000316
1998 lagC-null and gbf-null cells define key steps in the morphogenesis of Dictyostelium mounds. Developmental biology 31 9698452
1994 A GBF-binding site and a novel AT element define the minimal sequences sufficient to direct prespore-specific expression in Dictyostelium discoideum. Molecular and cellular biology 31 8065317
2007 KLF6 allelic loss is associated with tumor recurrence and markedly decreased survival in head and neck squamous cell carcinoma. International journal of cancer 30 17621627
1999 The promoter of the strictosidine synthase gene from periwinkle confers elicitor-inducible expression in transgenic tobacco and binds nuclear factors GT-1 and GBF. Plant molecular biology 30 10380815
1998 STF1 is a novel TGACG-binding factor with a zinc-finger motif and a bZIP domain which heterodimerizes with GBF proteins. The Plant journal : for cell and molecular biology 30 9721678
2020 mir-22-3p/KLF6/MMP14 axis in fibro-adipogenic progenitors regulates fatty infiltration in muscle degeneration. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 29 33000497
2020 lncRNA MIR4435-2HG promoted clear cell renal cell carcinoma malignant progression via miR-513a-5p/KLF6 axis. Journal of cellular and molecular medicine 29 33460239
2010 Klf6/copeb is required for hepatic outgrowth in zebrafish and for hepatocyte specification in mouse ES cells. Developmental biology 29 20430021
2002 The Kruppel-like factor Zf9 and proteins in the Sp1 family regulate the expression of HSP47, a collagen-specific molecular chaperone. The Journal of biological chemistry 29 12235161
2019 Metformin Counteracts HCC Progression and Metastasis Enhancing KLF6/p21 Expression and Downregulating the IGF Axis. International journal of endocrinology 27 30774659
2022 Bone marrow mesenchymal stem cell-derived extracellular vesicles containing miR-181d protect rats against renal fibrosis by inhibiting KLF6 and the NF-κB signaling pathway. Cell death & disease 26 35672285
2020 Hotspot mutant p53-R273H inhibits KLF6 expression to promote cell migration and tumor metastasis. Cell death & disease 26 32733026
2017 Up-regulation of miR-181a in clear cell renal cell carcinoma is associated with lower KLF6 expression, enhanced cell proliferation, accelerated cell cycle transition, and diminished apoptosis. Urologic oncology 26 29066014
2010 Nucleo-cytoplasmic localization domains regulate Krüppel-like factor 6 (KLF6) protein stability and tumor suppressor function. PloS one 26 20844588
2006 KLF6 degradation after apoptotic DNA damage. FEBS letters 26 17113081
2005 Induction of Zf9 in the kidney following early ischemia/reperfusion. Kidney international 26 16164628
2001 Klf6 is a zinc finger protein expressed in a cell-specific manner during kidney development. Journal of the American Society of Nephrology : JASN 26 11274234
2020 Paeonol Inhibits Cell Proliferation, Migration and Invasion and Induces Apoptosis in Hepatocellular Carcinoma by Regulating miR-21-5p/KLF6 Axis. Cancer management and research 24 32765094
2009 KLF6 inhibits estrogen receptor-mediated cell growth in breast cancer via a c-Src-mediated pathway. Molecular and cellular biochemistry 24 19707857
2020 Klf6 protects β-cells against insulin resistance-induced dedifferentiation. Molecular metabolism 23 32244185
2018 Expression of KLF6-SV2 in colorectal cancer and its impact on proliferation and apoptosis. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 23 29084019
2011 A small interfering RNA targeting the KLF6 splice variant, KLF6-SV1, as gene therapy for gastric cancer. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 23 21538018
2022 miR-106a-5p carried by tumor-derived extracellular vesicles promotes the invasion and metastasis of ovarian cancer by targeting KLF6. Clinical & experimental metastasis 22 35449340
2020 LncRNA LUCAT1/miR-181a-5p axis promotes proliferation and invasion of breast cancer via targeting KLF6 and KLF15. BMC molecular and cell biology 22 32998707
2004 Developmentally regulated expression of KLF6 in the mouse cornea and lens. Investigative ophthalmology & visual science 22 15557439
2022 KLF6 Promotes Pyroptosis of Renal Tubular Epithelial Cells in Septic Acute Kidney Injury. Shock (Augusta, Ga.) 21 34710881
2016 Interaction of KLF6 and Sp1 regulates basigin-2 expression mediated proliferation, invasion and metastasis in hepatocellular carcinoma. Oncotarget 21 27057625
1999 cDNA cloning and expression analysis of mouse zf9, a Krüppel-like transcription factor gene that is induced by adipogenic hormonal stimulation in 3T3-L1 cells. Biochimica et biophysica acta 21 10542316
2009 Targeted reduction of KLF6-SV1 restores chemotherapy sensitivity in resistant lung adenocarcinoma. Lung cancer (Amsterdam, Netherlands) 20 19328586
2023 Klf6 aggravates myocardial ischemia/reperfusion injury by activating Acsl4-mediated ferroptosis. The Kaohsiung journal of medical sciences 19 37530646
2023 Exosomal miR-181d-5p Derived from Rapamycin-Conditioned MDSC Alleviated Allograft Rejection by Targeting KLF6. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 19 37870185
2022 Long non-coding RNA ZFAS1 regulates cell proliferation and invasion in cervical cancer via the miR-190a-3p/KLF6 axis. Bioengineered 19 35112985
2020 Apremilast ameliorates ox-LDL-induced endothelial dysfunction mediated by KLF6. Aging 19 33052879
2019 Circular RNA circ-SMAD7 promoted ovarian cancer cell proliferation and metastasis by suppressing KLF6. European review for medical and pharmacological sciences 19 31298312
2016 A novel KLF6-Rho GTPase axis regulates hepatocellular carcinoma cell migration and dissemination. Oncogene 19 26876204
2016 Targeted knockdown of DJ-1 induces multiple myeloma cell death via KLF6 upregulation. Apoptosis : an international journal on programmed cell death 19 27734217
2023 TNF-α stimulated exosome derived from fibroblast-like synoviocytes isolated from rheumatoid arthritis patients promotes HUVEC migration, invasion and angiogenesis by targeting the miR-200a-3p/KLF6/VEGFA axis. Autoimmunity 18 37975481
2021 Circular RNA CircMTO1 suppressed proliferation and metastasis of osteosarcoma through miR-630/KLF6 axis. European review for medical and pharmacological sciences 18 33506896
2023 Nicotine induces macrophage pyroptosis via LINC01272/miR-515/KLF6 axis. Ecotoxicology and environmental safety 17 37478567
2014 GBF/Gea mutant with a single substitution sustains fungal growth in the absence of BIG/Sec7. FEBS letters 17 25451223
2013 The ArfGEF GBF-1 Is Required for ER Structure, Secretion and Endocytic Transport in C. elegans. PloS one 17 23840591
2009 Decreased expression of KLF6 and its significance in gastric carcinoma. Medical oncology (Northwood, London, England) 17 19967571
2008 Expression of the transcription factor Klf6 in cirrhosis, macronodules, and hepatocellular carcinoma. Journal of gastroenterology and hepatology 17 18171345
2024 Podocyte-specific KLF6 primes proximal tubule CaMK1D signaling to attenuate diabetic kidney disease. Nature communications 15 39271683
2005 Genomic organization and functional analysis of the gene encoding the Krüppel-like transcription factor KLF6. Biochimica et biophysica acta 15 16054710
2007 KLF6: mutational analysis and effect on cancer cell proliferation. International journal of oncology 14 17143513

Missed literature

Know a paper Affinage missed for KLF6? Flag it for the maintainers and the community.

No submissions yet.