Affinage

SP6

Transcription factor Sp6 · UniProt Q3SY56

Round 2 corrected
Length
376 aa
Mass
39.8 kDa
Annotated
2026-04-28
117 papers in source corpus 15 papers cited in narrative 15 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SP6 (Epiprofin) is a Krüppel-like C2H2 zinc finger transcription factor that functions as a master regulator of ectodermal organ development, governing the formation and differentiation of teeth, hair follicles, limbs, and epidermis (PMID:14551215, PMID:18297738). SP6 binds a CTg/aTAATTA consensus motif at promoters of enamel matrix genes (Amelx, Ambn, Enam), dentin genes (Dspp), and key transcription factors (Dlx2-5, Sp7, Pitx2), and positively autoregulates its own promoter (PMID:34662808). It participates in a positive feedback loop with Wnt/β-catenin signaling to promote cell junction assembly and BMP signaling in developing teeth, while in epidermis it exerts dose-dependent control of the cell cycle through Rb phosphorylation and Notch1 induction to balance proliferation and differentiation (PMID:22868911, PMID:25344255). Loss-of-function mutations in the zinc finger domain cause amelogenesis imperfecta by reducing DNA-binding affinity at enamel gene promoters and/or destabilizing the protein (PMID:32167558, PMID:22676574).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2003 High

    Identification of SP6 as a nuclear Krüppel-like zinc finger factor expressed in proliferating dental epithelium, hair follicle, and limb bud ectoderm established its candidacy as a multi-organ ectodermal regulator.

    Evidence cDNA cloning, in situ hybridization, and transfection/overexpression showing nuclear localization and enhanced cell proliferation in vitro

    PMID:14551215

    Open questions at the time
    • No target genes or DNA-binding site identified
    • Mechanism linking SP6 to proliferation undefined
  2. 2008 High

    Sp6 knockout mice revealed that SP6 is essential for development of teeth, hair, limbs, and lungs, connecting its broad expression pattern to non-redundant developmental requirements and linking its loss to apoptosis dysregulation.

    Evidence Full coding-region knockout mice with histology and apoptosis assays

    PMID:18297738

    Open questions at the time
    • Molecular targets mediating each organ phenotype unknown
    • Whether apoptosis is a direct or indirect consequence unclear
  3. 2011 Medium

    The discovery that SP6 protein is short-lived and degraded via the proteasome established post-translational regulation as a control mechanism, complementing transcriptional regulation of SP6 levels during amelogenesis.

    Evidence Proteasome inhibitor treatment, inducible SP6 expression system, Western blot vs. RT-PCR comparison in ameloblast-lineage cells

    PMID:22046099

    Open questions at the time
    • Ubiquitin ligase responsible for SP6 degradation not identified
    • Whether proteasomal regulation operates in non-dental tissues unknown
  4. 2012 High

    Reciprocal loss- and gain-of-function experiments demonstrated that SP6 promotes cell junction assembly and β-catenin accumulation, linking it to canonical Wnt signaling and BMP4 expression in tooth morphogenesis.

    Evidence Epfn−/− mice and Epfn overexpression in MDPC-23 cells; immunofluorescence and Western blot for junction proteins and β-catenin

    PMID:22868911

    Open questions at the time
    • Whether SP6 directly transcribes junction genes or acts indirectly unknown
    • Relative contribution of Wnt versus BMP arms not dissected
  5. 2012 High

    Identification of a frameshift mutation disrupting the third zinc finger of SP6 as causative for amelogenesis imperfecta, rescued by a wild-type transgene, proved that SP6 zinc finger integrity is required for enamel formation.

    Evidence Genetic linkage in AMI rats, cDNA sequencing, transgenic rescue with CMV-Sp6

    PMID:22676574

    Open questions at the time
    • Specific enamel gene promoters targeted by SP6 not yet defined at this point
    • Whether mutant protein exerts dominant-negative effects not tested
  6. 2014 High

    Compound Sp6;Sp8 ectodermal knockouts showed dose-dependent cooperation for AER formation and dorsal–ventral patterning via Fgf8, En1, and Wnt7a, placing SP6 as an indispensable mediator of Wnt/β-catenin and BMP signaling in limb ectoderm.

    Evidence Conditional compound knockout mice with in situ hybridization for downstream signaling targets

    PMID:25166858

    Open questions at the time
    • Direct transcriptional targets of SP6 vs. SP8 in limb not distinguished
    • Whether SP6 and SP8 bind identical or distinct DNA sites unclear
  7. 2014 High

    Dose-dependent roles of SP6 in epidermal keratinocyte biology were defined: low SP6 levels increase EGF-driven proliferation via Rb superphosphorylation, while high levels drive differentiation through E2F repression and Notch1 induction, explaining the thickened yet poorly differentiated epidermis of knockout mice.

    Evidence Epfn knockout mice, HaCaT overexpression, flow cytometry, Western blot for Rb, E2F, and Notch1

    PMID:25344255

    Open questions at the time
    • Whether SP6 directly binds Notch1 or Rb regulatory elements not shown
    • Mechanism of dose-dependent switch between proliferation and differentiation unclear
  8. 2020 High

    ChIP demonstrated that Msx2 directly binds the Sp6 promoter and activates its transcription, and together they repress follistatin, establishing the Msx2→SP6⊣Fst pathway in amelogenesis.

    Evidence ChIP for Msx2 at Sp6 promoter, siRNA and overexpression in LS8/G5 dental cells, Msx2 mutant mouse analysis

    PMID:33192593

    Open questions at the time
    • Whether SP6 directly binds Fst promoter or acts via intermediary not resolved
    • Relative contribution of Fst repression to overall ameloblast differentiation not quantified
  9. 2020 High

    A human SP6 missense variant (p.Ala273Lys) in the first zinc finger was shown by surface plasmon resonance to reduce binding to the AMBN promoter, providing the first direct DNA-binding mechanism for SP6-associated amelogenesis imperfecta in humans.

    Evidence Family genetic analysis; SPR comparing wild-type and mutant SP6 binding to AMBN promoter motif

    PMID:32167558

    Open questions at the time
    • Whether reduced AMBN transactivation alone explains the phenotype not tested
    • Full spectrum of SP6-regulated enamel genes affected by this mutation unknown
  10. 2021 High

    ChIP-seq defined the genome-wide SP6 binding consensus (CTg/aTAATTA) and identified direct targets including enamel/dentin matrix genes and developmental transcription factors, while reporter assays confirmed SP6 autoregulation, providing the first comprehensive target map.

    Evidence Whole-genome ChIP-seq, motif analysis, luciferase reporter assays, scRNA-seq co-expression

    PMID:34662808

    Open questions at the time
    • Functional validation of most ChIP-seq targets by loss-of-function not performed
    • Tissue-specific differences in SP6 cistrome not explored
  11. 2021 Medium

    A second missense mutation at the same codon (p.Ala273Met) was shown to destabilize the SP6 protein post-translationally, revealing that zinc finger mutations can impair SP6 function through protein instability in addition to reduced DNA binding.

    Evidence Western blot showing decreased mutant protein despite normal mRNA levels in a family with dominant AI

    PMID:33652941

    Open questions at the time
    • Degradation pathway for the destabilized mutant not characterized
    • Whether dominant-negative or haploinsufficiency mechanism operates not distinguished

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the E3 ubiquitin ligase governing SP6 proteasomal turnover, tissue-specific differences in the SP6 cistrome, the molecular basis of SP6's dose-dependent switch between proliferation and differentiation, and whether SP6 and SP8 share or partition direct transcriptional targets in limb and tooth development.
  • E3 ligase for SP6 degradation unidentified
  • No structural model of SP6–DNA complex exists
  • Tissue-specific ChIP-seq comparison between teeth, limb, and skin not performed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 3 GO:0140110 transcription regulator activity 3
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 2
Partners
CTNNB1MSX2SP8

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Epiprofin (SP6) was identified as a Krüppel-like factor family member containing three C2H2-type zinc finger motifs, expressed in proliferating dental epithelium, odontoblasts, hair follicle matrix epithelium, apical ectodermal ridge of limb buds, and posterior neuropore. Transfection of an epiprofin expression vector showed the protein localizes to the nucleus and promotes cell proliferation. cDNA cloning, in situ hybridization, whole-mount in situ hybridization, transfection/overexpression with nuclear localization and cell proliferation assays The Journal of biological chemistry High 14551215
2008 SP6 is required for normal development of skin (hair follicles), teeth, limbs, and lungs. Sp6 null mice are nude, lack functional teeth, and show limb and lung malformations. The Sp6 gene produces two transcripts (Sp6 and epiprofin) differing in the first exon but encoding the same protein. Developmental abnormalities in Sp6-null mice are associated with misregulation of apoptosis. Gene knockout (full coding region deletion) in mice, histology, apoptosis assays Developmental dynamics : an official publication of the American Association of Anatomists High 18297738
2011 In planarians, sp6-9 (the ortholog of vertebrate Sp6-9 group) is expressed specifically in the optic cup (not photoreceptor neurons) and is required for optic cup regeneration. RNAi knockdown of sp6-9 prevents formation of visible optic cups during regeneration by blocking generation of early optic cup progenitor cells from the neoblast stem cell population. Sp6-9 and Dlx function together as a module for optic cup development. RNAi knockdown in planarian regeneration model, in situ hybridization, cell lineage/progenitor analysis PLoS genetics High 21852957
2012 In Epfn (Sp6)-null mice, expression of tight junction and adherens junction proteins and β-catenin (a major effector of canonical Wnt signaling) is dramatically reduced in the developing tooth. Overexpression of Epfn in MDPC-23 dental pulp cells increases cellular accumulation of β-catenin, indicating upregulation of canonical Wnt/β-catenin signaling. Loss of cell junctions correlates with decreased BMP-4 expression, altered cell proliferation, and failure of ameloblast differentiation. Loss-of-function (Epfn−/− mice) and gain-of-function (Epfn overexpression in MDPC-23 cells), immunofluorescence/immunostaining, Western blot for junction proteins and β-catenin Cell and tissue research High 22868911
2012 A 2-bp insertional frameshift mutation in Sp6 (disrupting the third zinc finger domain) causes autosomal recessive amelogenesis imperfecta (AI) in AMI rats. Introduction of a wild-type Sp6 transgene into AMI rats rescued ameloblast function, confirming that SP6 loss is causative. The mutant SP6 protein is translated and localizes to the nucleus similarly to wild-type but lacks functional zinc finger activity. Tight spatiotemporal regulation of SP6 expression is critical for completing amelogenesis. Genetic linkage analysis, cDNA sequencing, transgenic rescue (CMV-Sp6 transgene in AMI rats), transfection/nuclear localization studies, histological analysis Orphanet journal of rare diseases High 22676574
2011 SP6 protein is short-lived and specifically degraded through the proteasome pathway in ameloblast-related cells. Regulation of SP6 protein stability (not mRNA level) is a crucial step in amelogenesis. Using an inducible SP6 expression system with siRNA knockdown, SP6 was linked to regulation of amelotin and Rock1 gene expression by microarray analysis. Inducible SP6 expression system, siRNA knockdown, proteasome inhibitor treatment, microarray gene expression analysis, Western blot vs. RT-PCR comparison Journal of biomedicine & biotechnology Medium 22046099
2014 Sp6 and Sp8 act together in the limb ectoderm in a dose-dependent manner to control AER (apical ectodermal ridge) formation and dorsal-ventral patterning. Combined elimination of Sp6 and Sp8 activity causes tetra-amelia: limb budding initiates but Fgf8 and En1 are not activated. Single Sp8 allele in Sp6-null background causes split-hand/foot malformation with double-dorsal digit tips and abnormal Wnt7a expansion to ventral ectoderm. Sp6 and Sp8 function as indispensable mediators of Wnt/β-catenin and BMP signaling in limb ectoderm. Conditional knockout mice (ectodermal-specific Sp6;Sp8 compound mutants), in situ hybridization for Fgf8, En1, Wnt7a, histology, genetic epistasis PLoS genetics High 25166858
2014 Epiprofin (Sp6) plays dual roles in epidermal keratinocyte development as a cell cycle regulator and transcription factor. Low Epfn expression increases HaCaT cell proliferation by increasing EGF responsiveness and superphosphorylation of Rb. High Epfn expression promotes cell cycle exit and differentiation by reducing E2F transactivation and inducing Notch1 expression. Epfn knockout mice have thickened epidermis with accumulation of p63-expressing premature transit amplifying cells with reduced proliferation and fewer differentiating Notch1-expressing keratinocytes. Epfn knockout mice, overexpression in HaCaT cells, flow cytometry cell cycle analysis, Western blot (Rb phosphorylation, E2F, Notch1), EGF responsiveness assays Journal of cell science High 25344255
2016 Wnt/β-catenin pathway activation at tooth initiation upregulates and ectopically expresses Epiprofin/Sp6 along with Shh and Fgf8 in the oral ectoderm, extending odontogenic potential. BMP4 downregulates Epfn expression during dental morphogenesis. A positive feedback loop exists where Epfn and β-catenin activate each other, and their balance is essential for proper tooth development and cusp patterning. In vitro tooth organ culture with GSK-3 inhibitor (BIO) to activate Wnt/β-catenin, RT-PCR and in situ hybridization for Epfn/Shh/Fgf/Bmp/Wnt markers, alkaline phosphatase activity assay Frontiers in cell and developmental biology Medium 27066482
2017 In the spider Parasteatoda tepidariorum, the Sp6-9 ortholog is expressed in developing appendages and its RNAi knockdown causes strong limb defects, loss of body segments, and head defects, revealing a conserved role in limb formation and an additional early role in head/body segment formation not previously described in arthropods. RNAi knockdown in spider embryos, in situ hybridization for expression analysis Development genes and evolution Medium 29116381
2018 An epistatic interaction between KRT25 and SP6 controls coat phenotype in horses. A missense variant in SP6 alone causes curly coat without hypotrichosis, whereas KRT25 variant masks the SP6 allele effect (epistasis), producing curly coat with hypotrichosis. This places SP6 downstream of KRT25 in the pathway controlling hair development. Genome-wide association analysis, whole-genome sequencing, variant filtering, allele combination analysis across horses with different coat phenotypes Scientific reports Low 29686323
2020 Msx2 directly binds to the Sp6 promoter (ChIP confirmed binding at putative Msx2 sites ~3.5 kb upstream) and activates Sp6 transcription. Sp6 and Msx2 work in concert to inhibit follistatin (Fst) expression during amelogenesis. Loss of Msx2 reduces Sp6 expression in secretory ameloblasts; silencing either Msx2 or Sp6 in dental epithelial cells upregulates Fst. Overexpression of Msx2 upregulates Sp6 and downregulates Fst, establishing an Msx2→Sp6→Follistatin pathway in late tooth development. ChIP assay (Msx2 binding to Sp6 promoter), siRNA knockdown, overexpression in dental epithelial cell lines (LS8, G5), Msx2 mutant mouse embryos, semi-qPCR and qRT-PCR, in situ hybridization Frontiers in physiology High 33192593
2020 A missense variant in SP6 (p.Ala273Lys, in the first zinc finger DNA-binding domain) causes autosomal dominant hypoplastic amelogenesis imperfecta. Surface plasmon resonance binding studies showed that wild-type SP6 binds more strongly to a potential SP6 binding motif in the AMBN (ameloblastin) proximal promoter than the mutant protein, indicating that reduced DNA-binding affinity of the zinc finger domain underlies the disease mechanism. Family-based genetic analysis, surface plasmon resonance (protein-DNA binding), bioinformatic identification of SP6 binding motif in AMBN promoter Human molecular genetics High 32167558
2021 Whole-genome ChIP-seq identified the consensus SP6 binding DNA motif as CTg/aTAATTA (nine nucleotides). SP6 target peaks were found in promoters of enamel and dentin matrix genes (Amelx, Ambn, Enam, Dspp), transcription factors (Dlx2, Dlx3, Dlx4, Dlx5, Sp6 itself, Sp7, Pitx2, Msx2), and extracellular matrix genes (Col1a2, Col11a2, Hapln1). Transcriptional reporter assays confirmed that SP6 co-expression enhanced Hapln1 and Sp6 own promoter activity, indicating SP6 autoregulates its own expression. ChIP-seq (whole-genome), bioinformatic motif analysis, single-cell RNA-seq UMAP clustering, luciferase transcriptional reporter assays Biochemical and biophysical research communications High 34662808
2021 A novel de novo missense mutation in SP6 (c.817_818delinsAT, p.Ala273Met) at the same nucleotide positions as a previously reported AI mutation causes severe hypoplastic amelogenesis imperfecta with an autosomal dominant inheritance. Western blot showed extremely decreased mutant protein levels compared to wild-type despite similar mRNA levels, indicating that the mutation destabilizes the SP6 protein post-translationally. Clinical genetic analysis, Western blot comparing mutant vs. wild-type SP6 protein and mRNA levels Genes Medium 33652941

Source papers

Stage 0 corpus · 117 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1984 Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic acids research 6483 6091052
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1984 Functional messenger RNAs are produced by SP6 in vitro transcription of cloned cDNAs. Nucleic acids research 1466 6207484
2009 A census of human transcription factors: function, expression and evolution. Nature reviews. Genetics 1191 19274049
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1986 Cloning of cDNA encoding the murine IgG1 induction factor by a novel strategy using SP6 promoter. Nature 561 3005865
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2011 Identification of an imprinted master trans regulator at the KLF14 locus related to multiple metabolic phenotypes. Nature genetics 250 21572415
1985 A novel transcription property of SP6 and T7 RNA polymerases: dependence on template structure. Nucleic acids research 205 2995921
2020 Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions. Nature cell biology 194 32203420
1982 Bacteriophage SP6-specific RNA polymerase. I. Isolation and characterization of the enzyme. The Journal of biological chemistry 190 7040372
1991 Preparative in vitro mRNA synthesis using SP6 and T7 RNA polymerases. Analytical biochemistry 144 1750668
2022 A comprehensive SARS-CoV-2-human protein-protein interactome reveals COVID-19 pathobiology and potential host therapeutic targets. Nature biotechnology 140 36217030
2013 Genome-wide association study of the rate of cognitive decline in Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association 140 23535033
2018 DNA methylation of the ELOVL2, FHL2, KLF14, C1orf132/MIR29B2C, and TRIM59 genes for age prediction from blood, saliva, and buccal swab samples. Forensic science international. Genetics 139 30300865
1985 Single stranded DNA SP6 promoter plasmids for engineering mutant RNAs and proteins: synthesis of a 'stretched' preproparathyroid hormone. Nucleic acids research 132 3858795
2018 Regulatory variants at KLF14 influence type 2 diabetes risk via a female-specific effect on adipocyte size and body composition. Nature genetics 124 29632379
2011 dlx and sp6-9 Control optic cup regeneration in a prototypic eye. PLoS genetics 118 21852957
2016 SPATA2-Mediated Binding of CYLD to HOIP Enables CYLD Recruitment to Signaling Complexes. Cell reports 115 27545878
2022 The transcription factor KLF14 regulates macrophage glycolysis and immune function by inhibiting HK2 in sepsis. Cellular & molecular immunology 93 34983946
1986 [pGlu6,Pro9]SP6-11, a selective agonist for the substance P P-receptor subtype. Journal of medicinal chemistry 88 2433445
2018 LncRNA HAND2-AS1 sponging miR-1275 suppresses colorectal cancer progression by upregulating KLF14. Biochemical and biophysical research communications 84 30078677
2015 Loss of KLF14 triggers centrosome amplification and tumorigenesis. Nature communications 84 26439168
1991 Specific contacts between the bacteriophage T3, T7, and SP6 RNA polymerases and their promoters. The Journal of biological chemistry 83 1985921
2004 Genomic analysis of bacteriophages SP6 and K1-5, an estranged subgroup of the T7 supergroup. Journal of molecular biology 80 14729334
2020 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. Cell reports 79 32814053
2003 The Krüppel-like factor epiprofin is expressed by epithelium of developing teeth, hair follicles, and limb buds and promotes cell proliferation. The Journal of biological chemistry 72 14551215
2007 Identification of the imprinted KLF14 transcription factor undergoing human-specific accelerated evolution. PLoS genetics 71 17480121
2015 Perhexiline activates KLF14 and reduces atherosclerosis by modulating ApoA-I production. The Journal of clinical investigation 67 26368306
2004 Complete genomic sequence of the virulent Salmonella bacteriophage SP6. Journal of bacteriology 66 15028677
2000 Identification of KLF13 and KLF14 (SP6), novel members of the SP/XKLF transcription factor family. Genomics 66 11087666
1987 Nucleotide sequence and expression of the cloned gene of bacteriophage SP6 RNA polymerase. Nucleic acids research 66 3031606
1985 Infectivity studies on different potato spindle tuber viroid (PSTV) RNAs synthesized in vitro with the SP6 transcription system. The EMBO journal 64 15938052
1986 Synthesis of the small subunit of ribulose-bisphosphate carboxylase from genes cloned into plasmids containing the SP6 promoter. The Biochemical journal 63 3827863
1986 Sequences of three promoters for the bacteriophage SP6 RNA polymerase. Nucleic acids research 57 3010240
1985 Transcription from bacteriophage T7 and SP6 RNA polymerase promoters in the presence of 3'-deoxyribonucleoside 5'-triphosphate chain terminators. Biochemistry 57 3002422
2010 Comparative validation of the SP6 antibody to Ki67 in breast cancer. Journal of clinical pathology 56 20671052
1993 Ultrastructure and chemical composition of the sheath of Leptothrix discophora SP-6. Journal of bacteriology 52 7504663
1991 Characterization of elongating T7 and SP6 RNA polymerases and their response to a roadblock generated by a site-specific DNA binding protein. Nucleic acids research 51 1891355
2020 CircTADA2A suppresses the progression of colorectal cancer via miR-374a-3p/KLF14 axis. Journal of experimental & clinical cancer research : CR 50 32799891
2018 LncRNA DGCR5 represses the development of hepatocellular carcinoma by targeting the miR-346/KLF14 axis. Journal of cellular physiology 50 30216442
1982 Bacteriophage SP6-specific RNA polymerase. II. Mapping of SP6 DNA and selective in vitro transcription. The Journal of biological chemistry 49 6279614
2016 Wnt/β-Catenin Regulates the Activity of Epiprofin/Sp6, SHH, FGF, and BMP to Coordinate the Stages of Odontogenesis. Frontiers in cell and developmental biology 46 27066482
1993 SP6 RNA polymerase efficiently synthesizes RNA from short double-stranded DNA templates. Nucleic acids research 46 7505427
2011 Involvement of Interleukin-10 in the Anti-Inflammatory Effect of Sanyinjiao (SP6) Acupuncture in a Mouse Model of Peritonitis. Evidence-based complementary and alternative medicine : eCAM 43 21799673
2014 Sp6 and Sp8 transcription factors control AER formation and dorsal-ventral patterning in limb development. PLoS genetics 39 25166858
2019 The KLF14 Transcription Factor Regulates Glycolysis by Downregulating LDHB in Colorectal Cancer. International journal of biological sciences 38 30745849
2005 Efficient RNA interference in zebrafish embryos using siRNA synthesized with SP6 RNA polymerase. Development, growth & differentiation 38 16026540
1989 Actions of tachykinins on the rabbit mesenteric artery: substance P and [Glp6,L-Pro9]SP6-11 are potent agonists for endothelial neurokinin-1 receptors. British journal of pharmacology 34 2477103
2022 KLF14 alleviated breast cancer invasion and M2 macrophages polarization through modulating SOCS3/RhoA/Rock/STAT3 signaling. Cellular signalling 33 34998931
2017 Dual host specificity of phage SP6 is facilitated by tailspike rotation. Virology 33 28456019
1990 The gene for Klebsiella bacteriophage K11 RNA polymerase: sequence and comparison with the homologous genes of phages T7, T3, and SP6. Molecular & general genetics : MGG 33 2370850
2022 Baihui (DU20), Shenmen (HT7) and Sanyinjiao (SP6) target the cAMP/CREB/BDNF and PI3K/Akt pathways to reduce central nervous system apoptosis in rats with insomnia. Heliyon 32 36636219
2017 Detection and evaluation of DNA methylation markers found at SCGN and KLF14 loci to estimate human age. Forensic science international. Genetics 32 28854399
2017 The KLF14 transcription factor regulates hepatic gluconeogenesis in mice. The Journal of biological chemistry 32 29123026
2002 Bacteriophage SP6 is closely related to phages K1-5, K5, and K1E but encodes a tail protein very similar to that of the distantly related P22. Journal of bacteriology 32 11976314
1998 Purification and characterization of a protein binding to the SP6 kappa promoter. A potential role for CArG-box binding factor-A in kappa transcription. The Journal of biological chemistry 32 9668064
2021 EZH2-mediated inhibition of KLF14 expression promotes HSCs activation and liver fibrosis by downregulating PPARγ. Cell proliferation 31 34031939
2020 Transcription Factor KLF14 and Metabolic Syndrome. Frontiers in cardiovascular medicine 31 32548128
2015 A novel role for KLF14 in T regulatory cell differentiation. Cellular and molecular gastroenterology and hepatology 31 25750932
1988 In vitro transcription and translational efficiency of chimeric SP6 messenger RNAs devoid of 5' vector nucleotides. Nucleic acids research 31 3260027
1987 Studies on SP6 promoter using a new plasmid vector that allows gene insertion at the transcription initiation site. Nucleic acids research 31 3031593
2018 Hypermethylation of TRIM59 and KLF14 Influences Cell Death Signaling in Familial Alzheimer's Disease. Oxidative medicine and cellular longevity 30 29849909
1993 Role of disulfide bonds in maintaining the structural integrity of the sheath of Leptothrix discophora SP-6. Journal of bacteriology 30 8253670
1986 Synthetic oligonucleotide tails inhibit in vitro and in vivo translation of SP6 transcripts of maize zein cDNA clones. Nucleic acids research 30 3456558
2020 The role of KLF14 in multiple disease processes. BioFactors (Oxford, England) 29 31925990
2008 The development of several organs and appendages is impaired in mice lacking Sp6. Developmental dynamics : an official publication of the American Association of Anatomists 29 18297738
1986 Structure of viroid replicative intermediates: physico-chemical studies on SP6 transcripts of cloned oligomeric potato spindle tuber viroid. Nucleic acids research 28 3808953
2017 Bacteriophage SP6 encodes a second tailspike protein that recognizes Salmonella enterica serogroups C2 and C3. Virology 27 28285722
2005 Role of the extracellular matrix proteins in the resistance of SP6.5 uveal melanoma cells toward cisplatin. International journal of oncology 25 15645125
1991 Functional modularity in the SP6 kappa promoter. Nucleic acids research 25 1909431
1988 Efficient in vitro expression of interferon alpha analogs using SP6 polymerase and rabbit reticulocyte lysate. Gene analysis techniques 25 3056802
2012 Epiprofin/Sp6 regulates Wnt-BMP signaling and the establishment of cellular junctions during the bell stage of tooth development. Cell and tissue research 24 22868911
1988 Transcription initiation site selection and abortive initiation cycling of phage SP6 RNA polymerase. The Journal of biological chemistry 24 3192528
2023 Efficacy of electroacupuncture stimulating Shenmen (HT7), Baihui (GV20), Sanyinjiao (SP6) on spatial learning and memory deficits in rats with insomnia induced by para-chlorophenylalanine: a single acupoint combined acupoints. Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan 23 37454255
2018 An epistatic effect of KRT25 on SP6 is involved in curly coat in horses. Scientific reports 23 29686323
2002 NYD-SP6, a novel gene potentially involved in regulating testicular development/spermatogenesis. Biochemical and biophysical research communications 23 11829468
1993 SP6 RNA polymerase containing vaccinia virus for rapid expression of cloned genes in tissue culture. BioTechniques 23 8431286
2014 Epiprofin orchestrates epidermal keratinocyte proliferation and differentiation. Journal of cell science 22 25344255
1991 SP6 RNA polymerase stutters when initiating from an AAA... sequence. Nucleic acids research 22 1891358
2018 DNA methylation of the Klf14 gene region in whole blood cells provides prediction for the chronic inflammation in the adipose tissue. Biochemical and biophysical research communications 21 29425818
2020 A missense variant in specificity protein 6 (SP6) is associated with amelogenesis imperfecta. Human molecular genetics 20 32167558
1986 In vitro translation of cucumoviral satellites. II. CARNA 5 from cucumber mosaic virus strain S and SP6 transcripts of cloned (S)CARNA 5 cDNA produce electrophoretically comigrating protein products. Virology 20 3487880
2019 KLF14 potentiates oxidative adaptation via modulating HO-1 signaling in castrate-resistant prostate cancer. Endocrine-related cancer 19 30400002
2018 Stimulation of KLF14/PLK1 pathway by thrombin signaling potentiates endothelial dysfunction in Type 2 diabetes mellitus. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 19 29710485
2023 KLF14 regulates the growth of hepatocellular carcinoma cells via its modulation of iron homeostasis through the repression of iron-responsive element-binding protein 2. Journal of experimental & clinical cancer research : CR 18 36600258
1986 Synthesis of epidermal growth factor (EGF) receptor in vitro using SP6 RNA polymerase-transcribed template mRNA. Biochimica et biophysica acta 18 3017432
2022 Differential Genetic and Epigenetic Effects of the KLF14 Gene on Body Shape Indices and Metabolic Traits. International journal of molecular sciences 16 35456983
2022 Upregulation of KLF14 expression attenuates kidney fibrosis by inducing PPARα-mediated fatty acid oxidation. Free radical biology & medicine 15 36584797
2021 Sp6/Epiprofin is a master regulator in the developing tooth. Biochemical and biophysical research communications 15 34662808
2013 Association of the KLF14 rs4731702 SNP and serum lipid levels in the Guangxi Mulao and Han populations. BioMed research international 15 24195066
2011 Possible linkage of SP6 transcriptional activity with amelogenesis by protein stabilization. Journal of biomedicine & biotechnology 15 22046099
2022 Adipocyte-Specific Modulation of KLF14 Expression in Mice Leads to Sex-Dependent Impacts on Adiposity and Lipid Metabolism. Diabetes 14 35081256
2019 Klf14 is an imprinted transcription factor that regulates placental growth. Placenta 14 31675530
2012 Inhibitory RNA aptamer against SP6 RNA polymerase. Biochemical and biophysical research communications 14 22426482
2012 Novel genetic linkage of rat Sp6 mutation to Amelogenesis imperfecta. Orphanet journal of rare diseases 14 22676574
2010 Epiprofin/Sp6: a new player in the regulation of tooth development. Histology and histopathology 14 20886441
1990 Nuclear transport of proteins translated in vitro from SP6 plasmid-generated mRNAs. Molecular and cellular biology 14 2137554
2024 KLF14 directly downregulates the expression of GPX4 to exert antitumor effects by promoting ferroptosis in cervical cancer. Journal of translational medicine 13 39390559
2023 Biochemical Activation and Regulatory Functions of Trans-Regulatory KLF14 and Its Association with Genetic Polymorphisms. Metabolites 13 36837818
2013 Involvement of KLF14 and egr-1 in the TGF-beta1 action on Leydig cell proliferation. Cytokine 13 23317878
2009 Molecular identification of (bla)SHV, (bla)LEN and (bla)OKP beta-lactamase genes in Klebsiella pneumoniae by bi-directional sequencing of universal SP6- and T7-sequence-tagged (bla)SHV-PCR amplicons. Molecular and cellular probes 13 19496249
2000 Characterization of a novel DNA primase from the Salmonella typhimurium bacteriophage SP6. Biochemistry 13 10677213
1994 Positive transcriptional control elements within the SP6 kappa promoter decamer 3' flanking sequence. Molecular immunology 13 8084335
1993 Two base pairs at -9 and -8 distinguish between the bacteriophage T7 and SP6 promoters. The Journal of biological chemistry 13 8366080
2022 KLF14 targets ITGB1 to inhibit the progression of cervical cancer via the PI3K/AKT signalling pathway. Discover oncology 12 35570248
2020 KLF14 inhibits osteogenic differentiation of human bone marrow mesenchymal stem cells by downregulating WNT3A. American journal of translational research 12 32913518
2020 An Msx2-Sp6-Follistatin Pathway Operates During Late Stages of Tooth Development to Control Amelogenesis. Frontiers in physiology 12 33192593
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2017 Expression and function of the zinc finger transcription factor Sp6-9 in the spider Parasteatoda tepidariorum. Development genes and evolution 11 29116381
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