Affinage

TGIF1

Homeobox protein TGIF1 · UniProt Q15583

Length
401 aa
Mass
43.0 kDa
Annotated
2026-06-10
59 papers in source corpus 24 papers cited in narrative 24 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

TGIF1 is a TALE-class homeodomain transcriptional co-repressor that restrains TGFβ/Nodal signaling and represses defined target genes to control embryonic patterning and adult cell-fate decisions (PMID:20040491, PMID:30060237). It engages DNA through its homeodomain, which recognizes the TGACA motif via the helix-α3 interface (R220/R221) and minor-groove contacts, with disease-associated mutations (P192A, R219C) destabilizing the fold and weakening DNA affinity (PMID:30060237, PMID:30048701, PMID:29355528). Its repressive output operates on two convergent axes against Smad signaling: the homeodomain directly contacts the Smad MH1 domain in a manner that occludes DNA binding (PMID:30060237), while a conserved C-terminal motif binds the SMAD2 MH2 domain at a surface overlapping coactivator-binding sites, displacing coactivators (PMID:40395157). Repression is enforced by a C-terminal SIN3A-interacting domain that folds into an amphipathic helix engaging the SIN3A PAH2 cleft (F379/L382/V383), the same element that mediates TGIF1 homodimerization (PMID:34884456, PMID:29179446). During development, TGIF1 (with TGIF2) limits Nodal-responsive transcription, and its requirement in extra-embryonic tissue is critical for proper epiblast patterning during gastrulation (PMID:20040491, PMID:27187787); it also represses Evi5l to support ciliogenesis and Shh signaling (PMID:27956704). In adult tissues, TGIF1 directly represses target genes to govern HSC quiescence and self-renewal (PMID:24100014), osteoblast differentiation and migration (repressing Pak3, mediating PTH anabolic action) (PMID:30902975, PMID:38661167), osteoclast differentiation via restriction of PP2A/ERK1/2 (PMID:40810487), pluripotency-factor levels in ESCs (binding Oct4/Nanog and HDAC1/2) (PMID:26411691), and EMT and cancer programs by antagonizing Twist1 in KRAS-driven pancreatic cancer (PMID:31268604, PMID:36057632). TGIF1 protein is degraded through phosphorylation-dependent recognition by the Fbxw7 E3 ligase substrate receptor (PMID:20622901).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 2010 High

    Established TGIF1 as a developmental brake on Nodal signaling, placing it upstream of Nodal-responsive transcription during gastrulation rather than merely a generic Smad partner.

    Evidence Conditional knockout mouse genetics with genetic epistasis against Nodal dosage reduction

    PMID:20040491

    Open questions at the time
    • Did not resolve which direct target genes mediate the Nodal-limiting effect
    • Tissue site of requirement not yet defined at this stage
  2. 2010 Medium

    Identified how TGIF1 protein levels are controlled, showing Fbxw7 mediates phosphorylation-dependent proteasomal turnover that tunes TGFβ-dependent transcription.

    Evidence Co-IP, ubiquitination assays, and growth/migration assays in cancer cell lines with Fbxw7 loss

    PMID:20622901

    Open questions at the time
    • Responsible kinase and phosphodegron not mapped
    • Single-lab functional readouts
  3. 2011 Medium

    Showed TGIF1 acts as a signal-frequency-decoding corepressor at a hormone-responsive promoter, expanding its repressive role beyond Smad signaling.

    Evidence ChIP, Fshb reporter assays, and overexpression of binding/phosphorylation-defective mutants under GnRH pulse stimulation

    PMID:21659477

    Open questions at the time
    • Corepressor complex recruited at Fshb not identified here
    • Single-lab study
  4. 2012 Medium

    Linked TGIF1 loss to elevated TGFβ signaling driving premature senescence, connecting its repressive function to cell-proliferation control.

    Evidence Tgif1-null primary MEFs with senescence/DNA-damage markers and TGFβ receptor kinase inhibitor rescue

    PMID:22514746

    Open questions at the time
    • Direct target genes mediating senescence not defined
    • Single-lab study
  5. 2012 Medium

    Defined a proinflammatory role for TGIF1 in endothelium, specifying p38 MAPK (not NF-κB) as the dependent pathway.

    Evidence Overexpression/siRNA in HUVECs with pathway-specific activation assays and in vivo radiation enteropathy model

    PMID:22995913

    Open questions at the time
    • Molecular link between TGIF1 and p38 activation not established
    • Whether transcriptional repression underlies this is unclear
  6. 2013 High

    Demonstrated TGIF1 suppresses HSC self-renewal and enforces quiescence, establishing an adult stem-cell function.

    Evidence CFU, competitive serial transplantation, and BrdU quiescence assays with loss- and gain-of-function

    PMID:24100014

    Open questions at the time
    • Direct HSC target genes not identified
    • Dependence on Smad signaling not tested
  7. 2014 Medium

    Showed TGIF1 can compete with an oncogenic homeodomain cofactor (MEIS1) on chromatin, providing a mechanism for tumor-suppressive differentiation in MLL-AML.

    Evidence ChIP of competitive occupancy at MEIS1-bound loci plus in vivo leukemia transplantation

    PMID:25349154

    Open questions at the time
    • Whether competition is for shared DNA sites or cofactors unresolved
    • Single-lab study
  8. 2015 Medium

    Revealed TGIF1 represses core pluripotency factors independently of TGFβ/activin/Nodal, broadening its mechanism to direct association with Oct4/Nanog and HDACs.

    Evidence Reciprocal Co-IP, ESC gain/loss-of-function, reporter assays, and pathway inhibitor controls

    PMID:26411691

    Open questions at the time
    • Direct promoter occupancy at pluripotency genes not fully mapped
    • Single-lab study
  9. 2015 Medium

    Connected TGIF1 to Smad2-dependent chondrogenic control by suppressing Smad2 phosphorylation and Sox9 expression in tendon stem cells.

    Evidence Co-IP, Smad2 phospho-Western, and in vivo rat tendon-bone repair model

    PMID:26599628

    Open questions at the time
    • Mechanism by which TGIF1 reduces Smad2 phosphorylation unclear
    • Single-lab study
  10. 2016 Medium

    Localized the developmental requirement for TGIF function to extra-embryonic tissue, showing it patterns the epiblast cell-non-autonomously.

    Evidence Epiblast-specific versus extra-embryonic conditional Cre-lox deletion in mouse

    PMID:20040491 PMID:27187787

    Open questions at the time
    • Signal relayed from extra-embryonic tissue to epiblast not identified
  11. 2016 Medium

    Implicated TGIF1-SIN3A complex integrity in sustaining Wnt target expression and cancer invasion, demonstrated by SID decoy disruption.

    Evidence SID decoy peptides, TGIF1 knockdown, Wnt reporters, β-catenin imaging, and invasion assays

    PMID:29179446

    Open questions at the time
    • Direct molecular link between TGIF1-SIN3A and Wnt/β-catenin unclear
    • Tier 3 mechanistic chain
  12. 2017 High

    Identified Evi5l as a direct TGIF target and connected TGIF repression to ciliogenesis and Shh signaling via genetic rescue.

    Evidence Transcriptome profiling, ChIP at the Evi5l TGIF site, Evi5l-knockdown rescue, and cilia/Shh readouts

    PMID:27956704

    Open questions at the time
    • How Evi5l levels mechanistically alter cilia number not fully defined
  13. 2018 High

    Determined the structural basis of TGIF1 DNA recognition and dual Smad-occluding function, plus how HPE mutations destabilize the fold.

    Evidence Crystal structure with DNA, NMR, ITC, HDX-MS/CEST NMR, and reporter assays across three structural studies

    PMID:29355528 PMID:30048701 PMID:30060237

    Open questions at the time
    • Structure of the full TGIF1-Smad-DNA assembly not solved
    • Conformational dynamics of release from promoters not directly observed
  14. 2018 Medium

    Placed TGIF1 within an HPE gene-regulatory network by showing ZIC2 directly activates Tgif1 transcription.

    Evidence ChIP, in vitro DNA binding, and ZBS reporter assays

    PMID:29391420

    Open questions at the time
    • In vivo developmental relevance of the ZIC2→TGIF1 link not tested
    • Single-lab study
  15. 2019 High

    Established TGIF1 as an essential mediator of PTH anabolic bone action and an osteoblast differentiation regulator coupling formation and resorption.

    Evidence Osteoblast/osteocyte conditional KO, histomorphometry, PTH treatment, and Sema3E secretion assays

    PMID:30902975

    Open questions at the time
    • Direct TGIF1 targets in the PTH program not fully enumerated here
  16. 2019 High

    Showed TGIF1 restrains KRAS-driven pancreatic cancer by antagonizing Twist1, with phosphorylation switching off this tumor-suppressive function.

    Evidence Co-IP, conditional KO PDAC models, Twist1-ablation genetic epistasis, and phosphorylation experiments

    PMID:31268604

    Open questions at the time
    • Kinase mediating KRAS/MAPK-dependent TGIF1 phosphorylation not pinned down at the residue level
  17. 2021 High

    Defined the structural basis of the TGIF1-SIN3A corepressor interaction and revealed competition between SIN3A binding and homodimerization.

    Evidence NMR structure of TGIF1-SID/SIN3A-PAH2, mutagenesis, and ITC

    PMID:34884456

    Open questions at the time
    • Functional consequence of the dimerization/SIN3A competition in cells not tested
  18. 2022 Medium

    Identified a TFEB→TGIF1 axis that represses TGFβ-driven EMT in epicardial cells.

    Evidence Promoter reporters, qRT-PCR, TGIF1-silencing rescue, and in vivo epicardial TFEB overexpression

    PMID:36057632

    Open questions at the time
    • Direct TGIF1 EMT target genes not mapped
    • Single-lab study
  19. 2024 High

    Mechanistically linked TGIF1 repression of Pak3 to osteoblast adhesion, spreading, and migration required for bone regeneration.

    Evidence Conditional KO osteoblasts, adhesion/migration assays on collagen I, ChIP for Pak3 repression, and in vivo regeneration/PTH models

    PMID:38661167

    Open questions at the time
    • How Pak3 elevation impairs focal adhesions at molecular detail not fully resolved
  20. 2025 High

    Extended TGIF1 function to osteoclasts, showing it promotes differentiation by restricting PP2A and sustaining ERK1/2 phosphorylation.

    Evidence Osteoclast-lineage conditional KO, PP2A-inhibition rescue, ERK1/2 phospho-analysis, and aging bone-loss model

    PMID:40810487

    Open questions at the time
    • Whether TGIF1 transcriptionally represses PP2A subunits not directly shown
  21. 2025 Medium

    Mapped a conserved TGIF1 motif binding the SMAD2 MH2 surface at coactivator-overlapping sites, defining a second molecular axis for Smad repression.

    Evidence NMR titration, HDX-MS, AlphaFold3 modeling, and BiFC validation

    PMID:40395157

    Open questions at the time
    • Coactivator displacement not directly demonstrated competitively
    • Relies partly on AlphaFold3 modeling rather than full experimental structure
  22. 2025 Medium

    Implicated TGIF1 in metabolic regulation through a miR-106b-5p/EGR2 axis in a type 2 diabetes model.

    Evidence ChIP at miR-106b-5p promoter, dual-luciferase reporters, and TGIF1 overexpression with rescue in T2D mice

    PMID:39842865

    Open questions at the time
    • Mechanism reconciling TGIF1 acting as activator of miR-106b-5p versus its canonical repressor role unexplained
    • Single-lab study

Open questions

Synthesis pass · forward-looking unresolved questions
  • The kinase(s) and precise phosphodegron coupling TGIF1 phosphorylation to Fbxw7-mediated turnover and to inactivation of its tumor-suppressive functions remain undefined.
  • Responsible kinase(s) not identified
  • Phosphosite mapping incomplete
  • Link between degradation and target-gene selection unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0003677 DNA binding 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1266738 Developmental Biology 3 R-HSA-74160 Gene expression (Transcription) 3
Complex memberships
SIN3A-HDAC corepressor complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 Tgif1 and Tgif2 act as transcriptional co-repressors that limit the response to Nodal signaling during gastrulation; genetic reduction of Nodal dose partially rescues gastrulation defects in Tgif1/Tgif2 double-null embryos, placing Tgifs upstream of Nodal-responsive transcription in early embryogenesis. Conditional knockout mouse genetics, genetic epistasis with Nodal dosage reduction Development (Cambridge, England) High 20040491
2010 The E3 ubiquitin ligase substrate-recognition factor Fbxw7 targets TGIF1 for proteasomal degradation in a phosphorylation-dependent manner; inactivation of Fbxw7 leads to accumulation of phosphorylated TGIF1 and repression of TGFβ-dependent transcription, thereby attenuating TGFβ-regulated cell growth and migration. Co-immunoprecipitation, ubiquitination assays, cancer cell lines with Fbxw7 loss-of-function mutations, cell growth and migration assays Oncogene Medium 20622901
2018 The TGIF1 homeodomain (HD) binds the TGACA DNA motif through both the HD core/major groove and the N-terminal arm/minor groove; additionally, the TGIF1-HD directly interacts with the MH1 domain of Smad proteins, and this HD-MH1 interaction partially occludes the DNA-binding site of the complex, providing a mechanism by which TGIF1 is released from promoters to actively repress Smad-induced TGFβ signaling. Crystal structure of TGIF1-HD bound to DNA, NMR, in vitro binding assays, functional reporter assays Nucleic acids research High 30060237
2019 Tgif1 is a PTH target gene in osteoblasts; deletion of Tgif1 in osteoblasts/osteocytes impairs osteoblast differentiation and reduces bone formation, and also decreases bone resorption by increasing secretion of the osteoclast-inhibiting factor Semaphorin 3E (Sema3E). PTH failed to increase bone formation in Tgif1-deficient mice, identifying Tgif1 as an essential component of PTH anabolic action. Conditional knockout mice, bone histomorphometry, PTH treatment experiments, Sema3E secretion assays Nature communications High 30902975
2013 Tgif1 regulates hematopoietic stem cell (HSC) quiescence and self-renewal; Tgif1-null bone marrow cells show greater self-renewal, reduced proliferation, and increased quiescence, whereas Tgif1 overexpression increases proliferation but reduces long-term survival in transplant assays, indicating Tgif1 suppresses stem cell self-renewal. CFU assays, competitive repopulation/serial transplantation in mice, BrdU labeling for quiescence Molecular and cellular biology High 24100014
2015 Tgif1 directly represses core pluripotency factors (Oct4, Sox2, Nanog) in mouse embryonic stem cells independently of TGFβ/activin/nodal signaling; Tgif1 physically associates with Oct4, Nanog, and HDAC1/2, counterbalancing the autoregulatory amplification of core pluripotency factors. Co-immunoprecipitation, overexpression and knockdown in ESCs, reporter assays, treatment with activin/nodal pathway inhibitors Cell reports Medium 26411691
2012 Primary MEFs lacking Tgif1 senesce prematurely, accumulate increased DNA damage, and are more sensitive to TGFβ-mediated growth inhibition; treatment with a TGFβ receptor kinase inhibitor rescues proliferation of Tgif1-null MEFs, demonstrating that elevated TGFβ signaling in the absence of Tgif1 contributes to premature senescence. Primary MEF culture, proliferation assays, senescence markers (SA-β-gal), DNA damage markers (γH2AX), TGFβ receptor kinase inhibitor treatment PloS one Medium 22514746
2011 TGIF1 functions as a GnRH pulse-frequency-sensitive corepressor of FSHβ gene transcription; overexpression of binding- or phosphorylation-defective TGIF1 mutants fails to repress Fshb promoter activity, and TGIF1 occupies the FSHβ promoter in a cyclical manner after GnRH stimulation as shown by ChIP. Chromatin immunoprecipitation (ChIP), Fshb promoter reporter assays, siRNA knockdown, overexpression of TGIF1 mutants, GnRH pulse experiments Molecular endocrinology (Baltimore, Md.) Medium 21659477
2017 TGIF1 binds to a conserved consensus TGIF site 5' of the Evi5l gene and represses its expression; loss of both Tgif1 and Tgif2 increases Evi5l expression, reduces primary cilia numbers in MEFs, and impairs the Shh transcriptional response; reducing Evi5l in double-null MEFs partially restores cilia numbers and Shh signaling. Transcriptome profiling, ChIP, Evi5l knockdown rescue experiments, cilia quantification by microscopy, Shh pathway reporter assays Molecular and cellular biology High 27956704
2018 NMR structure of TGIF1-HD (TALE-type homeodomain) determined; holoprosencephaly-associated mutations P192A and R219C disrupt packing of helices α1 and α2 against α3, destabilize the HD structure, and reduce DNA-binding affinity by 23-fold and 10-fold respectively, as measured by isothermal titration calorimetry. NMR structure determination, circular dichroism, isothermal titration calorimetry, 1H-15N HSQC of P192A mutant Biochemical and biophysical research communications High 29355528
2018 ZIC2 (an HPE-causative transcription factor) directly binds to Zic2-binding sites (ZBS) on the 5' flanking region of the Tgif1 gene and activates Tgif1 transcription, as demonstrated by ChIP and in vitro DNA binding assays; ZBS are required for Zic2-dependent transcriptional activation in reporter assays, linking two HPE-causative genes in a direct regulatory relationship. Chromatin immunoprecipitation (ChIP), in vitro DNA binding assays, reporter gene assays Scientific reports Medium 29391420
2019 TGIF1 associates with Twist1 and inhibits Twist1 expression and activity; KrasG12D/MAPK-mediated TGIF1 phosphorylation suppresses this function in human PDACs; ablating Twist1 in KrasG12D;Tgif1KO mice completely blunts PDAC formation, establishing that TGIF1 restrains KrasG12D-driven PDAC through antagonism of Twist1. Co-immunoprecipitation, conditional knockout mouse PDAC models, genetic epistasis (Twist1 ablation rescue), mechanistic phosphorylation experiments The EMBO journal High 31268604
2014 TGIF1 interferes with MEIS1-dependent transcriptional programs in MLL-rearranged AML by associating with MEIS1-bound chromatin regions in a competitive manner; forced TGIF1 expression promotes differentiation and cell cycle exit in MLL-AF9-transformed cells and delays leukemic onset in vivo. ChIP, in vitro differentiation and cell cycle assays, in vivo leukemia transplantation model, gene expression analysis Leukemia Medium 25349154
2012 TGIF1 plays a role in TNF-α- and radiation-induced proinflammatory phenotype of endothelial cells; TGIF1 knockdown inhibits both TNF-α- and radiation-induced p38 MAPK pathway activation (but not NF-κB activation), and TGIF1 deficiency reduces radiation-induced proinflammatory cytokine expression in vivo, identifying p38 MAPK as the signaling pathway through which TGIF1 promotes inflammation. TGIF1 overexpression and siRNA knockdown in HUVECs, p38 MAPK and NF-κB pathway activation assays, in vivo radiation enteropathy model with Tgif1-/- mice The Journal of biological chemistry Medium 22995913
2021 TGIF1 utilizes a C-terminal SIN3A-interacting domain (SID) that adopts an amphipathic helix to bind the hydrophobic cleft of SIN3A PAH2; residues F379, L382, and V383 are critical for binding; the same SID also mediates TGIF1 homodimerization, suggesting a competitive relationship between dimerization and SIN3A-PAH2 binding. NMR structure determination of TGIF1-SID bound to SIN3A PAH2, mutagenesis of critical residues, ITC binding assays International journal of molecular sciences High 34884456
2018 The helix α3 of TGIF1-HD constitutes the primary DNA-binding interface as determined by hydrogen-deuterium exchange mass spectrometry (HDX-MS) and confirmed by CEST NMR spectroscopy; residues R220 and R221 in α3 are crucial for DNA binding, and DNA binding induces conformational changes in α1 and α2 as well. HDX-MS, CEST NMR spectroscopy, NMR titration Biochimica et biophysica acta. Proteins and proteomics High 30048701
2025 A vertebrate-conserved short motif (I302-L310) of TGIF1 binds to a groove on the SMAD2 MH2 domain surface that overlaps with coactivator binding sites; BiFC assays confirmed that the α2-β8 loop of SMAD2-MH2 is key for TGIF1 binding, suggesting TGIF1 represses TGFβ signaling by competing with coactivators for SMAD2-MH2 binding. NMR titration, HDX-MS, AlphaFold3 modeling, bimolecular fluorescence complementation (BiFC) assays FEBS letters Medium 40395157
2024 Tgif1 acts as a transcriptional repressor of p21-activated kinase 3 (Pak3) in osteoblasts; absence of Tgif1 leads to increased Pak3 expression, which impairs focal adhesion formation, osteoblast spreading, and migration on collagen type I matrices; Tgif1 is also required for osteoblast recruitment to bone surfaces during regeneration and PTH 1-34 treatment in vivo. Conditional KO osteoblasts, cell morphology and adhesion assays, migration assays on collagen I, ChIP/transcriptional repression assays for Pak3, in vivo bone regeneration and PTH treatment models eLife High 38661167
2025 Tgif1 is expressed in osteoclast precursors with increasing expression during RANKL/M-CSF-induced differentiation; cell-autonomous deletion of Tgif1 in the osteoclast lineage impairs differentiation and resorption capacity; mechanistically, Tgif1 restricts ERK1/2 dephosphorylation by suppressing protein phosphatase 2A (PP2A), and PP2A inhibition restores differentiation of Tgif1-deficient osteoclasts. Conditional KO in osteoclast lineage, in vitro differentiation assays, PP2A inhibition rescue, ERK1/2 phosphorylation analysis, in vivo aging bone loss model Journal of bone and mineral research High 40810487
2022 TFEB transcriptionally activates TGIF1 expression by binding the Tgif1 promoter; in epicardial cells, TFEB overexpression prevents TGFβ-induced EMT, and this effect is abolished by Tgif1 silencing, establishing a TFEB→TGIF1 axis that represses TGFβ-driven EMT. Reporter assays, qRT-PCR, TGIF1 silencing rescue experiments, in vitro EMT assays, in vivo epicardial TFEB overexpression mouse model Nature communications Medium 36057632
2016 TGIF1 interacts with the PAH2 domain of SIN3A; SID decoy peptides that disrupt this interaction dissociate TGIF1 from the SIN3A complex, inhibit Wnt target gene expression, reduce nuclear β-catenin, and suppress cancer cell invasion; TGIF1 knockdown phenocopies SID decoy effects on Wnt targets and invasion. SID decoy peptide treatment, TGIF1 knockdown, Wnt reporter assays, β-catenin localization by immunofluorescence, Transwell invasion assays Oncotarget Medium 29179446
2015 TGIF1 represses Sox9 expression by interacting with TGFβ-activated Smad2, suppressing Smad2 phosphorylation, and thereby inhibiting chondrogenic differentiation of tendon-derived stem cells; TGIF1 silencing upregulates chondrogenic markers and increases fibrocartilage formation at the tendon-bone interface in a rat model. siRNA knockdown, TGIF1 overexpression in TDSCs, Co-IP for Smad2 interaction, Western blot for Smad2 phosphorylation, in vivo rat tendon repair model Cellular physiology and biochemistry Medium 26599628
2016 Tgif1 deficiency in extra-embryonic tissue (but not epiblast) is the critical cause of gastrulation failure in Tgif1/Tgif2 double-null embryos; a single wild-type allele of Tgif1 in extra-embryonic tissue rescues gastrulation, demonstrating that extra-embryonic Tgif function is required for patterning the epiblast. Epiblast-specific conditional deletion of Tgif1 using Cre-lox genetics PloS one (Tgif1 and Tgif2 Regulate Axial Patterning in Mouse) Medium 20040491 27187787
2025 TGIF1 is enriched on the miR-106b-5p promoter and promotes miR-106b-5p expression; miR-106b-5p in turn suppresses EGR2; in a T2D mouse model, TGIF1 overexpression reduces hyperglycemia and lipid accumulation through the miR-106b-5p/EGR2 axis, and miR-106b-5p inhibition or EGR2 overexpression partially reverses the TGIF1 effect. ChIP for TGIF1 at miR-106b-5p promoter, dual-luciferase reporter assays, TGIF1 overexpression in T2D mice, rescue experiments BMJ open diabetes research & care Medium 39842865

Source papers

Stage 0 corpus · 59 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Tgif1 and Tgif2 regulate Nodal signaling and are required for gastrulation. Development (Cambridge, England) 56 20040491
2010 Tumor suppressor Fbxw7 regulates TGFβ signaling by targeting TGIF1 for degradation. Oncogene 42 20622901
2018 TGIF1 homeodomain interacts with Smad MH1 domain and represses TGF-β signaling. Nucleic acids research 39 30060237
2019 TG-interacting factor 1 (Tgif1)-deficiency attenuates bone remodeling and blunts the anabolic response to parathyroid hormone. Nature communications 37 30902975
2018 Inhibition of microRNA-23b prevents polymicrobial sepsis-induced cardiac dysfunction by modulating TGIF1 and PTEN. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 35 29710503
2011 Gonadotropin-releasing hormone pulse sensitivity of follicle-stimulating hormone-beta gene is mediated by differential expression of positive regulatory activator protein 1 factors and corepressors SKIL and TGIF1. Molecular endocrinology (Baltimore, Md.) 32 21659477
2020 HDAC3 deteriorates colorectal cancer progression via microRNA-296-3p/TGIF1/TGFβ axis. Journal of experimental & clinical cancer research : CR 30 33203425
2019 Loss of the transcriptional repressor TGIF1 results in enhanced Kras-driven development of pancreatic cancer. Molecular cancer 30 31109321
2015 TGIF1 promoted the growth and migration of cancer cells in nonsmall cell lung cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 27 26104768
2013 Tgif1 regulates quiescence and self-renewal of hematopoietic stem cells. Molecular and cellular biology 26 24100014
2017 MicroRNA-23b-3p regulates human keratinocyte differentiation through repression of TGIF1 and activation of the TGF-ß-SMAD2 signalling pathway. Experimental dermatology 25 27306475
2015 Tgif1 Counterbalances the Activity of Core Pluripotency Factors in Mouse Embryonic Stem Cells. Cell reports 25 26411691
2013 Homeobox gene transforming growth factor β-induced factor-1 (TGIF-1) is a regulator of villous trophoblast differentiation and its expression is increased in human idiopathic fetal growth restriction. Molecular human reproduction 25 23761267
2019 TGIF1 functions as a tumor suppressor in pancreatic ductal adenocarcinoma. The EMBO journal 24 31268604
2012 Premature senescence and increased TGFβ signaling in the absence of Tgif1. PloS one 24 22514746
2012 The TGF-β/Smad repressor TG-interacting factor 1 (TGIF1) plays a role in radiation-induced intestinal injury independently of a Smad signaling pathway. PloS one 20 22567107
2022 The TFEB-TGIF1 axis regulates EMT in mouse epicardial cells. Nature communications 18 36057632
2020 Breast cancer bone metastases are attenuated in a Tgif1-deficient bone microenvironment. Breast cancer research : BCR 18 32272947
2012 The TG-interacting factor TGIF1 regulates stress-induced proinflammatory phenotype of endothelial cells. The Journal of biological chemistry 17 22995913
2014 TGIF1 is a negative regulator of MLL-rearranged acute myeloid leukemia. Leukemia 16 25349154
2017 A mouse-to-man candidate gene study identifies association of chronic otitis media with the loci TGIF1 and FBXO11. Scientific reports 15 28970529
2016 Targeted interference of SIN3A-TGIF1 function by SID decoy treatment inhibits Wnt signaling and invasion in triple negative breast cancer cells. Oncotarget 15 29179446
2020 TGIF1 and SF1 polymorphisms are associated with litter size in Small Tail Han sheep. Reproduction in domestic animals = Zuchthygiene 14 32594576
2015 TGIF1 Gene Silencing in Tendon-Derived Stem Cells Improves the Tendon-to-Bone Insertion Site Regeneration. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 14 26599628
2013 TGIF1 splicing variant 8 is overexpressed in oral squamous cell carcinoma and is related to pathologic and clinical behavior. Oral surgery, oral medicine, oral pathology and oral radiology 14 24119525
2022 Silencing of histone deacetylase 3 suppresses the development of esophageal squamous cell carcinoma through regulation of miR-494-mediated TGIF1. Cancer cell international 13 35578338
2017 Tgif1 and Tgif2 Repress Expression of the RabGAP Evi5l. Molecular and cellular biology 13 27956704
2020 TGIF1-Twist1 axis in pancreatic ductal adenocarcinoma. Computational and structural biotechnology journal 12 33005315
2020 RETRACTED: KDM5B-mediated microRNA-448 up-regulation restrains papillary thyroid cancer cell progression and slows down tumor growth via TGIF1 repression. Life sciences 11 32147429
2013 TGIF1 is a potential candidate gene for high myopia in ethnic Kashmiri population. Current eye research 11 24215395
2021 The homeobox gene TGIF1 is required for chicken ovarian cortical development and generation of the juxtacortical medulla. Development (Cambridge, England) 10 34387307
2024 MircoRNA-25-3p in skin precursor cell-induced Schwann cell-derived extracellular vesicles promotes axon regeneration by targeting Tgif1. Experimental neurology 8 38492636
2021 TGIF1 plays a carcinogenic role in esophageal squamous cell carcinoma through the Wnt/β‑catenin and Akt/mTOR signaling pathways. International journal of molecular medicine 8 33693954
2021 Single-nucleotide polymorphisms in FLT3, NLRP5, and TGIF1 are associated with litter size in Small-tailed Han sheep. Archives animal breeding 8 35024433
2016 Tgif1 and Tgif2 Regulate Axial Patterning in Mouse. PloS one 8 27187787
2020 The Chinese Medicine, Shezhi Huangling Decoction, Inhibits the Growth and Metastasis of Glioma Cells via the Regulation of miR-1298-5p/TGIF1 Axis. Cancer management and research 7 32765071
2023 Circular RNA CDR1as Mediated by Human Antigen R (HuR) Promotes Gastric Cancer Growth via miR-299-3p/TGIF1 Axis. Cancers 6 38067260
2011 Detection of TGIF1 homeobox gene in oral squamous cell carcinoma according to histologic grading. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics 6 21237437
2020 XTP8 stimulates migration and invasion of gastric carcinoma through interacting with TGIF1. European review for medical and pharmacological sciences 5 32196592
2018 Structural insights into the impact of two holoprosencephaly-related mutations on human TGIF1 homeodomain. Biochemical and biophysical research communications 5 29355528
2018 Link between the causative genes of holoprosencephaly: Zic2 directly regulates Tgif1 expression. Scientific reports 5 29391420
2016 Homeobox gene TGIF-1 is increased in placental endothelial cells of human fetal growth restriction. Reproduction (Cambridge, England) 5 27539603
2013 Tgif1 and SnoN modified chondrocytes or stem cells for tendon-bone insertion regeneration. Medical hypotheses 5 23747175
2025 Mechanism of TGIF1 on glycolipid metabolism disorders in mice with type 2 diabetes. BMJ open diabetes research & care 4 39842865
2025 Novel IgG and IgA autoantibodies validated in two independent cohorts are associated with disease activity and determine organ manifestations in systemic lupus erythematosus: implications for anti-LIN28A, anti-HMGN5, anti-IRF5, and anti-TGIF1. Annals of the rheumatic diseases 4 40348637
2021 Structural Insight into the Binding of TGIF1 to SIN3A PAH2 Domain through a C-Terminal Amphipathic Helix. International journal of molecular sciences 4 34884456
2023 Molecular characterization and effects of the TGIF1 gene on proliferation and steroidogenesis in yak (Bos grunniens) granulosa cells. Theriogenology 3 37660474
2021 TGIF1 Knockdown Inhibits the Proliferation and Invasion of Gastric Cancer via AKT Signaling Pathway. Cancer management and research 3 33776478
2017 Genetic Variants Contributing to Colistin Cytotoxicity: Identification of TGIF1 and HOXD10 Using a Population Genomics Approach. International journal of molecular sciences 3 28335481
2019 Backbone and side chain resonance assignments of the C-terminal domain of human TGIF1. Biomolecular NMR assignments 2 31388821
2025 Improved Litter Size in Thin-Tailed Indonesian Sheep Through Analysis of TGIF1 Gene Polymorphisms. Veterinary medicine international 1 40297328
2025 Structural insights into the binding of human TGIF1 with SMAD2 MH2 domain. FEBS letters 1 40395157
2024 Tgif1-deficiency impairs cytoskeletal architecture in osteoblasts by activating PAK3 signaling. eLife 1 38661167
2018 Characterization of the interaction interface and conformational dynamics of human TGIF1 homeodomain upon the binding of consensus DNA. Biochimica et biophysica acta. Proteins and proteomics 1 30048701
2026 STC2 promotes anoikis resistance by modulating TGIF1 mRNA stability in colorectal cancer. Frontiers in cell and developmental biology 0 41696444
2025 Tgif1-deficiency impairs osteoclast differentiation through PP2A-mediated ERK1/2 dephosphorylation and attenuates bone loss in mice. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 0 40810487
2024 [Effect of CircCCND1 on the Malignant Biological Behaviors of H446 Lung Cancer Cells by Regulating the MiR-340-5p/TGIF1 Axis]. Zhongguo fei ai za zhi = Chinese journal of lung cancer 0 38590190
2020 A Fateful Decision: Tgif1 and Cardiac Neural Crest Identity. Developmental cell 0 32369738
2019 A novel G26A variation in 5' half of TGIF1 gene associates with high myopia in ethnic Kashmiri population from India. Taiwan journal of ophthalmology 0 33437604

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