Affinage

GLI1

Zinc finger protein GLI1 · UniProt P08151

Length
1106 aa
Mass
117.9 kDa
Annotated
2026-06-10
100 papers in source corpus 24 papers cited in narrative 24 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

GLI1 is a zinc-finger transcription factor and terminal effector of the Hedgehog pathway that binds DNA through its zinc-finger domain to activate target gene transcription, and disrupting this DNA contact with the small molecule Glabrescione B suppresses Hedgehog-dependent tumor growth and stem cell self-renewal (PMID:25476449). GLI1 autoregulates its own expression through Gli-binding sites in its first intron and engages the histone variant H2A.Z at chromatin, establishing a positive transcriptional feedback loop (PMID:31085420), and directly activates a broad target program including DNMT1/DNMT3a (PMID:22110720), DNMT3A upon autophagy induction (PMID:35226587), NEK2A (PMID:28035348), basonuclin (PMID:15313903), and MMP2/MMP9/procollagen-I (PMID:35595725). GLI1 activity is gated by an extensive kinase network: ERK2 phosphorylation at S102/S116/S130 cooperatively weakens GLI1–SUFU binding to license nuclear transcriptional activity (PMID:35831023), whereas MEKK2/3 phosphorylation reduces GLI1 stability and DNA binding while enhancing SUFU association downstream of FGF2 (PMID:29662197), and Plk1 phosphorylation at S481 drives nuclear export and SUFU binding in a cell-cycle-dependent manner (PMID:30578313). Protein-level stability is set opposingly by the deubiquitinase USP48, which removes ubiquitin from GLI1 in a reciprocal positive feedback loop (PMID:28623188), and the chaperonin subunit CCT2, which folds GLI1 and shields it from β-TrCP-mediated degradation (PMID:31462707). GLI1 is further regulated by physical sequestration by β-catenin (PMID:25645196), ADAR1-mediated A-to-I RNA editing that enhances its activity (PMID:29203771), and non-canonical inputs from STAT3 (PMID:35595725), YAP1/PI3K-AKT (PMID:31957872), ULK3 (PMID:35226587), and Arhgap36 (PMID:25024229). Genetically, Gli1 regulates hematopoietic stem cell quiescence and myeloid progenitor proliferation (PMID:20107231) and maintains peripheral nerve architecture through endoneurial fibroblasts independently of Hedgehog signaling (PMID:34772739).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 2004 Medium

    Establishing that GLI1 acts as a direct sequence-specific transcriptional activator required showing it binds a defined promoter element and drives target expression in a disease context.

    Evidence Gli-luciferase reporter with promoter mutagenesis and EMSA on the basonuclin promoter in basal cell carcinoma

    PMID:15313903

    Open questions at the time
    • Limited to one target gene
    • Did not address GLI1 post-translational regulation
  2. 2006 Medium

    Defining how GLI is switched off in the absence of Hedgehog clarified the kinase cascade converting full-length GLI to a repressor form.

    Evidence Biochemical phosphorylation and ubiquitination assays compiling PKA/GSK3/CKI-primed SCF(Slimb/β-TRCP) processing in Drosophila and mammalian cells (review)

    PMID:17102630

    Open questions at the time
    • Review compiling others' data
    • Focus on repressor processing, not GLI1 activation
  3. 2008 Medium

    Identifying negative regulators downstream of Smoothened placed PKCδ in the pathway as a suppressor of GLI1 output.

    Evidence Gli-luciferase reporter, siRNA knockdown, and cyclopamine epistasis in mammalian cells

    PMID:19015273

    Open questions at the time
    • No direct GLI1 phosphorylation site mapped
    • Mechanism of GLI1 inhibition not defined
  4. 2010 Medium

    Genetic deletion revealed an organismal role for Gli1 in regulating hematopoietic stem cell quiescence and myeloid proliferation.

    Evidence Gli1 homozygous knockout mouse with HSC/progenitor functional, transplantation, and Cyclin D1 assays

    PMID:20107231

    Open questions at the time
    • Direct GLI1 target genes in HSCs not defined
    • Did not separate canonical vs non-canonical contributions
  5. 2011 Medium

    Linking GLI1 to epigenetic machinery showed it directly controls DNA methyltransferase expression and downstream gene methylation.

    Evidence ChIP at the DNMT1 promoter, knockdown/overexpression, and methylation-specific PCR in pancreatic cancer

    PMID:22110720

    Open questions at the time
    • DNMT3a regulation is indirect
    • Genome-wide methylation consequences not mapped
  6. 2014 High

    Demonstrating that the zinc-finger/DNA interface is druggable established GLI1's DNA-binding domain as the functional and therapeutic core.

    Evidence Structural analysis, small-molecule (Glabrescione B) binding/interference assay, Gli-luciferase reporter, and in vitro/in vivo tumor assays

    PMID:25476449

    Open questions at the time
    • No high-resolution GLI1–DNA co-structure reported here
    • Effect on non-canonical GLI1 activation not addressed
  7. 2014 Medium

    A non-canonical, Smoothened-independent activator (Arhgap36) was identified that promotes full-length GLI accumulation via the cilium and SUFU interaction.

    Evidence Genome-scale cDNA overexpression screen, co-IP with SUFU, cilia imaging, and KIF3A/IFT88 epistasis

    PMID:25024229

    Open questions at the time
    • Direct vs indirect SUFU modulation unclear
    • Physiological contexts of Arhgap36-GLI1 axis not defined
  8. 2015 Medium

    Cross-talk with Wnt was established by showing β-catenin physically sequesters and destabilizes GLI1 to suppress Hedgehog output.

    Evidence Co-IP, proximity ligation assay, Gli-luciferase reporter, cell-cycle analysis, and in vivo medulloblastoma transplantation

    PMID:25645196

    Open questions at the time
    • Interaction interface not mapped
    • Single lab without reciprocal genetic validation
  9. 2016 Medium

    GLI1 was shown to nucleate a negative feedback loop by directly transactivating NEK2A, which stabilizes the inhibitor SUFU.

    Evidence ChIP at the NEK2A promoter, reporter assay, and SUFU stability measurements

    PMID:28035348

    Open questions at the time
    • Kinetics of feedback not quantified
    • Generalizability across tissues untested
  10. 2017 High

    Opposing the repressor-processing pathway, USP48 was identified as a deubiquitinase that directly stabilizes GLI1, forming a positive feedback loop sustaining Hedgehog signaling.

    Evidence Co-IP, deubiquitinase activity assay, ChIP, reporter, and glioblastoma tumorigenesis assays

    PMID:28623188

    Open questions at the time
    • Ubiquitin chain linkage specificity not defined
    • Site of deubiquitination on GLI1 unmapped
  11. 2017 Medium

    An RNA-level regulatory layer was uncovered: ADAR1-mediated A-to-I editing of GLI1 enhances its transcriptional activity and drives drug resistance.

    Evidence RNA editing analysis, catalytic-mutant ADAR1 comparison, reporter assay, and patient-derived xenografts in multiple myeloma

    PMID:29203771

    Open questions at the time
    • Edited residue effect on GLI1 protein not mechanistically dissected
    • Editing prevalence across tissues unknown
  12. 2018 High

    MEKK2/3 were defined as inhibitory kinases that destabilize GLI1, reduce its DNA binding, and enhance SUFU association downstream of FGF2.

    Evidence In vitro kinase assay, co-IP, DNA-binding assay, reporter, and medulloblastoma proliferation assays

    PMID:29662197

    Open questions at the time
    • Exact phosphosites only partially mapped
    • In vivo relevance of FGF2-MEKK axis not tested
  13. 2019 High

    Plk1 was shown to impose cell-cycle control on GLI1 by phosphorylating S481 to drive nuclear export and SUFU binding.

    Evidence In vitro kinase assay, mutagenesis, subcellular fractionation, co-IP, and reporter assay

    PMID:30578313

    Open questions at the time
    • Nuclear export machinery for GLI1 not identified
    • Consequences for cell-cycle-coupled target gene timing not detailed
  14. 2019 Medium

    GLI1 was shown to autoregulate via intronic Gli-binding sites and engage H2A.Z chromatin, defining a self-amplifying transcriptional loop.

    Evidence EMSA with GBS mutants, reporter assays with deletion constructs, ChIP for histone marks/BRD4, and co-IP with H2A.Z

    PMID:31085420

    Open questions at the time
    • Functional consequence of H2A.Z interaction unresolved
    • Quantitative contribution of autoregulation in vivo unclear
  15. 2019 Medium

    A chaperonin requirement was established: CCT2 folds GLI1 and protects it from β-TrCP-mediated degradation under hypoxia.

    Evidence Mass spectrometry interaction screen, co-IP, ubiquitination assay, knockdown, and xenograft model

    PMID:31462707

    Open questions at the time
    • GLI1 folding intermediates not characterized
    • Hypoxia-specificity mechanism not defined
  16. 2019 Medium

    ULK3 was connected to autophagy-driven GLI1 activation at the DNMT3A promoter, extending GLI1 into autophagy signaling.

    Evidence Proximity ligation assay, ChIP at DNMT3A promoter, shRNA knockdown, and reporter assay

    PMID:35226587

    Open questions at the time
    • Direct ULK3 phosphorylation of GLI1 not demonstrated
    • Physiological autophagy contexts not broadly tested
  17. 2020 Medium

    ERK2-equivalent and cross-pathway inputs were clarified, with YAP1/PI3K-AKT cross-talk shown to reciprocally amplify GLI1 in esophageal carcinoma.

    Evidence Co-IP, knockdown, and in vitro/in vivo tumor growth assays

    PMID:31957872

    Open questions at the time
    • GLI1-YAP1 interaction interface unmapped
    • Direct vs indirect transcriptional cooperation unresolved
  18. 2020 Low

    PRMT-mediated arginine methylation was reported as a modulator of GLI1 activity and stability with context-dependent direction.

    Evidence In vitro methylation, co-IP, reporter, and stability assays compiled in a review-like paper

    PMID:32859041

    Open questions at the time
    • Findings compiled from multiple sources, not primary data here
    • Methylation sites and direction of effect not directly demonstrated
  19. 2020 Medium

    RAB23 was positioned as an upstream negative regulator acting both canonically and via pERK1/2 to restrain GLI1 in osteoprogenitors.

    Evidence Rab23 knockout mouse, western blot for GLI1/pERK1/2, pharmacological ERK inhibition rescue, and histology

    PMID:32662771

    Open questions at the time
    • Direct RAB23 mechanism on GLI1 not shown
    • Separation of canonical vs ERK contributions incomplete
  20. 2021 Medium

    Lineage tracing and knockout revealed a Hedgehog-independent role for Gli1 in endoneurial fibroblasts maintaining peripheral nerve architecture.

    Evidence Gli1-Cre fate mapping, conditional/constitutive knockout, ultrastructural nerve analysis, and Dhh-null comparison

    PMID:34772739

    Open questions at the time
    • Driver of Hedgehog-independent Gli1 expression unknown
    • Target genes in endoneurial fibroblasts not identified
  21. 2022 High

    ERK2 was defined as a direct activating kinase that phosphorylates S102/S116/S130 to cooperatively release GLI1 from SUFU.

    Evidence In vitro kinase assay, mutagenesis, quantitative binding affinity, and phosphomimetic reporter experiments

    PMID:35831023

    Open questions at the time
    • Upstream ERK-activating signals into GLI1 not fully traced
    • In vivo relevance of the >25-fold affinity shift untested
  22. 2022 Medium

    STAT3 was identified as a direct transcriptional inducer of GLI1, with GLI1 driving fibrotic gene expression in myelofibrosis.

    Evidence ChIP at the GLI1 promoter, luciferase reporter, knockdown, and immunofluorescence in fibrocytes

    PMID:35595725

    Open questions at the time
    • STAT3-GLI1 axis specificity across tissues unclear
    • Whether STAT3 also modulates GLI1 protein activity not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many opposing post-translational, RNA-editing, and cross-pathway inputs are integrated to set net GLI1 transcriptional output in a given cellular context remains unresolved.
  • No unified model reconciling activating (ERK2, USP48, CCT2) and inhibitory (Plk1, MEKK2/3, β-catenin) inputs
  • Lack of high-resolution GLI1-DNA structure
  • Mechanism of Hedgehog-independent GLI1 expression undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 3
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 1 GO:0005929 cilium 1
Pathway
R-HSA-1643685 Disease 6 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 4
Partners
CCT2CTNNB1H2AFZSUFUUSP48YAP1

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 GLI1 binds DNA through its zinc finger domain, and Glabrescione B was identified as the first small molecule that binds to the GLI1 zinc finger domain and impairs GLI1 transcriptional activity by interfering with its interaction with DNA, inhibiting Hedgehog-dependent tumor cell growth and stem cell self-renewal in vitro and in vivo. Structural analysis of GLI1 zinc finger/DNA interaction, small molecule binding assay, Gli-luciferase reporter assay, in vitro and in vivo tumor growth assays The EMBO journal High 25476449
2017 The deubiquitinase USP48 directly interacts with GLI1 and cleaves ubiquitin from GLI1, thereby stabilizing GLI1 protein and activating Gli-dependent transcription. In turn, GLI1 transcriptionally activates USP48, forming a positive feedback loop to sustain Hedgehog signaling. Co-immunoprecipitation, deubiquitinase activity assay, Gli-luciferase reporter, siRNA knockdown, glioblastoma cell proliferation and tumorigenesis assays, chromatin immunoprecipitation EMBO reports High 28623188
2022 ERK2 MAP kinase phosphorylates GLI1 on three evolutionarily conserved sites (S102, S116, S130) near the SUFU binding region, and multisite phosphorylation cooperatively weakens GLI1-SUFU binding affinity by over 25-fold, facilitating GLI1 nuclear transcriptional activity. In vitro kinase assay, site-directed mutagenesis, binding affinity measurements, Gli-luciferase reporter in mammalian cells, phosphomimetic substitution experiments Life science alliance High 35831023
2018 MEKK2 (MAP3K2) and MEKK3 (MAP3K3) phosphorylate GLI1 on multiple Ser/Thr sites, reducing GLI1 protein stability, DNA-binding ability, and increasing GLI1 association with SUFU, thereby inhibiting GLI1 transcriptional activity. MEKK2/3 mediate FGF2-induced inhibition of Hedgehog signaling. Co-immunoprecipitation, in vitro kinase assay, Gli-luciferase reporter, site-directed mutagenesis, medulloblastoma cell proliferation assays Oncogene High 29662197
2019 Polo-like kinase 1 (Plk1) phosphorylates GLI1 at S481, promoting nuclear export of GLI1 and increasing its association with the negative regulator SUFU, thereby reducing Hedgehog signaling activity. GLI1 expression peaks during G1/S phases and is suppressed by Plk1 during other cell cycle phases. In vitro kinase assay, site-directed mutagenesis, co-immunoprecipitation, subcellular fractionation/nuclear export assay, Gli-luciferase reporter Journal of cell science High 30578313
2008 Protein kinase Cδ (PKCδ) negatively regulates GLI1 transcriptional activity downstream of Smoothened; activated PKCδ decreases Gli-luciferase reporter activity and endogenous GLI1 and PTCH1 expression, while PKCδ siRNA increases these targets. Gli-luciferase reporter assay, siRNA knockdown, western blot, epistasis experiment (cyclopamine rescue with PKCδ siRNA) The Journal of biological chemistry Medium 19015273
2006 In the absence of Hedgehog, sequential phosphorylation of Gli by PKA, GSK3, and CKI creates docking sites for the SCF(Slimb/β-TRCP) E3 ubiquitin ligase, promoting Gli ubiquitination and proteasome-mediated proteolytic processing to a truncated transcriptional repressor form. Biochemical phosphorylation assays, ubiquitination assays, proteasome inhibition experiments in Drosophila and mammalian cells Cell cycle (Georgetown, Tex.) Medium 17102630
2015 Stabilized β-catenin physically interacts with GLI1 protein, leading to GLI1 sequestration, reduced GLI1 transcriptional activity, and GLI1 degradation, resulting in suppression of Hedgehog signaling, reduced medulloblastoma cell proliferation, G2/M arrest, and promotion of a senescent-like state. Co-immunoprecipitation, proximity ligation assay, Gli-luciferase reporter, cell cycle analysis, medulloblastoma sphere assays, in vivo tumor transplantation Molecular cancer Medium 25645196
2017 ADAR1-mediated Alu-dependent adenosine-to-inosine RNA editing of GLI1 enhances GLI1 transcriptional activity and promotes Hedgehog pathway activation; wild-type but not catalytically mutant ADAR1 drives this editing and increases GLI1-mediated transcription, promoting immunomodulatory drug resistance in multiple myeloma. RNA editing analysis, ADAR1 wild-type vs. mutant expression, GLI1 transcriptional reporter assay, siRNA knockdown, patient-derived xenograft transplantation Nature communications Medium 29203771
2014 Arhgap36 activates GLI transcription factors in a Smoothened-independent manner by inhibiting Gli repressor formation, promoting accumulation of full-length Gli proteins in the primary cilium, and functionally interacting with Suppressor of Fused (SUFU). Arhgap36-induced Gli activation requires KIF3A and IFT88, indicating ciliogenesis is required. Genome-scale cDNA overexpression screen, Gli-luciferase reporter, co-immunoprecipitation with SUFU, cilia accumulation imaging, genetic epistasis with KIF3A/IFT88 knockdown, transcriptional profiling Proceedings of the National Academy of Sciences of the United States of America Medium 25024229
2011 GLI1 directly regulates DNMT1 gene expression in pancreatic cancer; ChIP assay showed GLI1 protein binds to the DNMT1 promoter. GLI1 also regulates DNMT3a expression, though not through direct promoter binding. GLI1-mediated regulation of DNMT1 affects APC gene methylation. ChIP assay, siRNA knockdown, lentiviral overexpression, qRT-PCR, western blot, methylation-specific PCR PloS one Medium 22110720
2019 ULK3 (unc-51 like kinase 3) activates GLI1, and ULK3-dependent GLI1 activation contributes to transcriptional upregulation of DNMT3A gene expression upon autophagy induction; proximity ligation assay and ChIP confirmed GLI1 activity at the DNMT3A promoter. Proximity ligation assay, ChIP, shRNA knockdown, qRT-PCR, Gli-luciferase reporter Autophagy Medium 35226587
2020 PRMT1 methylates GLI1 to upregulate its transcriptional activity and target gene expression; cytoplasmic PRMT5 methylates GLI1 and promotes GLI1 protein stabilization. Nuclear PRMT5 indirectly downregulates GLI1 activity via MENIN-mediated suppression of GAS1 expression. In vitro methylation assay, co-immunoprecipitation, Gli-luciferase reporter, protein stability assays (reviewed from multiple studies) Cells Low 32859041
2016 GLI1 and Gli2 directly bind to promoter regions of the NEK2A gene and induce its transcription, as demonstrated by chromatin immunoprecipitation; Nek2A in turn stabilizes SUFU and negatively regulates Hedgehog target genes, forming a negative feedback loop. Chromatin immunoprecipitation, Gli-luciferase reporter, protein stability assay, mRNA/protein expression analysis International journal of oncology Medium 28035348
2019 GLI1 and GLI2 bind Gli binding sites (GBS) within the first intron of the human GLI1 gene in vitro, and elimination of key GBS attenuates transcriptional activation, demonstrating that GLI1 auto-regulates its own expression through a positive feedback loop. GLI1 also binds the histone variant H2A.Z. Electrophoretic mobility shift assay (in vitro DNA binding), transcriptional reporter assays with GBS mutants, ChIP for histone marks and BRD4, co-immunoprecipitation of GLI1 with H2A.Z DNA repair Medium 31085420
2019 In hypoxic colorectal cancer cells, CCT2 (T-complex protein 1 subunit beta) interacts with GLI1 and promotes proper folding of GLI1, protecting it from ubiquitination-mediated degradation by β-TrCP; CCT2 knockdown inhibits GLI1-driven tumor growth. Mass spectrometry interaction screen, co-immunoprecipitation, ubiquitination assay, siRNA knockdown, in vivo xenograft model Oncogene Medium 31462707
2020 GLI1 physically interacts with YAP1 in esophageal squamous cell carcinoma cells, as demonstrated by co-immunoprecipitation; GLI1 upregulates YAP1 in a LATS1-independent manner, while YAP1 induces GLI1 expression via PI3K/AKT signaling, and their interaction promotes tumor growth in vitro and in vivo. Co-immunoprecipitation, siRNA knockdown, western blot, in vitro and in vivo tumor growth assays Journal of cellular physiology Medium 31957872
2022 STAT3 directly induces GLI1 gene expression in myelofibrosis fibrocytes; chromatin immunoprecipitation and luciferase assay showed STAT3 binds the GLI1 promoter and activates transcription. GLI1 in turn activates MMP2, MMP9, and procollagen-I expression, contributing to bone marrow fibrosis. Chromatin immunoprecipitation, luciferase reporter assay, siRNA knockdown, western blot, immunofluorescence Cell death & disease Medium 35595725
2004 Gli proteins bind to a Gli-binding site in the promoter of the basonuclin gene and transcriptionally activate basonuclin expression, linking Hedgehog-Gli pathway activation to enhanced rRNA transcription in basal cell carcinoma. Gli-luciferase reporter with promoter deletion/mutation, electrophoretic mobility shift assay, in vivo BCC tissue analysis Cancer research Medium 15313903
2018 Trichostatin A (a histone deacetylase inhibitor) promotes proteasome-dependent GLI1 protein degradation in multiple myeloma cells and inhibits nuclear accumulation of GLI1; p21 induction also contributes to GLI1 downregulation at the transcriptional level. Immunofluorescence for GLI1 nuclear localization, immunoprecipitation for ubiquitination, western blot, qPCR, proteasome inhibitor rescue experiment Cancer management and research Low 30214285
2016 In the MALAT1-GLI1 fusion identified in plexiform fibromyxoma, the truncated GLI1 protein retains its capacity to transcriptionally activate target genes, demonstrated by PCR/sequencing validation of fusion transcript and GLI1 protein overexpression with retained transcriptional activity. PCR on genomic DNA, Sanger sequencing, FISH, immunohistochemistry, transcriptional activation assay The Journal of pathology Low 27101025
2010 Genetic deletion of Gli1 in mice reveals that Gli1 regulates hematopoietic stem cell quiescence and myeloid progenitor proliferation; Gli1-null mice show increased quiescent long-term HSCs with enhanced engraftment, decreased myeloid colony formation, impaired G-CSF response, and reduced Cyclin D1 levels in progenitor cells. Gli1 homozygous knockout mouse, HSC/progenitor functional assays, transplantation/engraftment, colony formation assay, western blot for Cyclin D1 Blood Medium 20107231
2021 Gli1 marks peripheral nerve perineurial glia, endoneurial fibroblasts, and pericytes by genetic fate mapping; Gli1 null mice show normal perineurium but form endoneurial minifascicles, demonstrating that Gli1 functions specifically in endoneurial fibroblasts to maintain normal peripheral nerve architecture. Gli1 expression in endoneurial fibroblasts is independent of Hedgehog/Dhh signaling (noncanonical). Genetic fate mapping (Gli1-Cre lineage tracing), Gli1 conditional and constitutive knockout, histological and ultrastructural analysis of peripheral nerves, Dhh null comparison The Journal of neuroscience : the official journal of the Society for Neuroscience Medium 34772739
2020 RAB23 acts as an upstream negative regulator of canonical Hh-GLI1 signaling and also non-canonically regulates GLI1 through pERK1/2; in Rab23-deficient mice, both canonical HH signaling and FGF10-driven pERK1/2 are elevated, leading to elevated GLI1 expression and aberrant osteoprogenitor proliferation causing craniosynostosis. Rab23 knockout mouse, western blot for GLI1/pERK1/2, pharmacological ERK inhibition with normalization of GLI1, histological analysis, genetic epistasis eLife Medium 32662771

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Gli and hedgehog in cancer: tumours, embryos and stem cells. Nature reviews. Cancer 592 12044012
2011 Gli proteins in development and disease. Annual review of cell and developmental biology 578 21801010
2016 Targeting the Sonic Hedgehog Signaling Pathway: Review of Smoothened and GLI Inhibitors. Cancers 462 26891329
2006 Signaling from Smo to Ci/Gli: conservation and divergence of Hedgehog pathways from Drosophila to vertebrates. Development (Cambridge, England) 387 16339192
2007 The Gli code: an information nexus regulating cell fate, stemness and cancer. Trends in cell biology 305 17845852
2002 Hedgehog-Gli signalling and the growth of the brain. Nature reviews. Neuroscience 288 11823802
2017 Gli1 identifies osteogenic progenitors for bone formation and fracture repair. Nature communications 286 29230039
1998 Combinatorial Gli gene function in floor plate and neuronal inductions by Sonic hedgehog. Development (Cambridge, England) 205 9584120
1999 Gli proteins and Hedgehog signaling: development and cancer. Trends in genetics : TIG 204 10498938
2021 Hedgehog/GLI Signaling Pathway: Transduction, Regulation, and Implications for Disease. Cancers 184 34298625
2012 Hedgehog-Gli pathway activation during kidney fibrosis. The American journal of pathology 180 22342522
2003 Gli proteins and the control of spinal-cord patterning. EMBO reports 174 12897799
2020 Hedgehog Signaling and Truncated GLI1 in Cancer. Cells 155 32957513
2014 Gli1/DNA interaction is a druggable target for Hedgehog-dependent tumors. The EMBO journal 155 25476449
2017 Yap/Taz Deletion in Gli+ Cell-Derived Myofibroblasts Attenuates Fibrosis. Journal of the American Society of Nephrology : JASN 149 28768710
1999 Gli genes in development and cancer. Oncogene 147 10630638
2019 Gli Proteins: Regulation in Development and Cancer. Cells 145 30754706
2015 Ptch1 and Gli regulate Shh signalling dynamics via multiple mechanisms. Nature communications 120 25833741
2016 Recurrent MALAT1-GLI1 oncogenic fusion and GLI1 up-regulation define a subset of plexiform fibromyxoma. The Journal of pathology 112 27101025
2017 Gastroblastoma harbors a recurrent somatic MALAT1-GLI1 fusion gene. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 109 28731043
2017 Alu-dependent RNA editing of GLI1 promotes malignant regeneration in multiple myeloma. Nature communications 106 29203771
2015 Targeting GLI factors to inhibit the Hedgehog pathway. Trends in pharmacological sciences 102 26072120
2006 Regulation of Hh/Gli signaling by dual ubiquitin pathways. Cell cycle (Georgetown, Tex.) 102 17102630
2012 Hedgehog pathway and GLI1 isoforms in human cancer. Discovery medicine 101 22369969
2019 GLI1-amplifications expand the spectrum of soft tissue neoplasms defined by GLI1 gene fusions. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 100 31189998
2010 Gli1 regulates the proliferation and differentiation of HSCs and myeloid progenitors. Blood 99 20107231
2021 GLI1: A Therapeutic Target for Cancer. Frontiers in oncology 93 34113570
1997 Expression of indian hedgehog, bone morphogenetic protein 6 and gli during skeletal morphogenesis. Mechanisms of development 93 9486541
1999 Expression of ptc and gli genes in talpid3 suggests bifurcation in Shh pathway. Development (Cambridge, England) 76 10225999
2011 Expression of DNMT1 and DNMT3a are regulated by GLI1 in human pancreatic cancer. PloS one 73 22110720
2017 Gli1-induced deubiquitinase USP48 aids glioblastoma tumorigenesis by stabilizing Gli1. EMBO reports 72 28623188
2019 Next-Generation Hedgehog/GLI Pathway Inhibitors for Cancer Therapy. Cancers 70 30991683
2007 Sonic hedgehog-Gli1 pathway in colorectal adenocarcinomas. World journal of gastroenterology 68 17461467
2014 Sonic hedgehog and Gli1 expression predict outcome in resected pancreatic adenocarcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 64 25552484
2023 The Critical Role of The Piezo1/β-catenin/ATF4 Axis on The Stemness of Gli1+ BMSCs During Simulated Microgravity-Induced Bone Loss. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 63 37759400
2015 Aberrant GLI1 Activation in DNA Damage Response, Carcinogenesis and Chemoresistance. Cancers 62 26633513
2018 Targeting GLI Transcription Factors in Cancer. Molecules (Basel, Switzerland) 61 29695137
2011 Timing of Sonic hedgehog and Gli1 expression segregates midbrain dopamine neurons. The Journal of comparative neurology 52 21713771
2020 The SHH/GLI signaling pathway: a therapeutic target for medulloblastoma. Expert opinion on therapeutic targets 51 32990091
2012 Gli-similar proteins: their mechanisms of action, physiological functions, and roles in disease. Vitamins and hormones 50 22391303
2015 β-Catenin-Gli1 interaction regulates proliferation and tumor growth in medulloblastoma. Molecular cancer 49 25645196
2012 Canonical and noncanonical Hedgehog/GLI signaling in hematological malignancies. Vitamins and hormones 49 22391298
2005 Interference with HH-GLI signaling inhibits prostate cancer. Trends in molecular medicine 46 15882606
1999 Developmental pathways: Sonic hedgehog-Patched-GLI. Environmental health perspectives 46 10064544
2018 Role and inhibition of GLI1 protein in cancer. Lung Cancer (Auckland, N.Z.) 44 29628779
2016 Hedgehog Gli signalling in kidney fibrosis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 43 27229466
2014 Down-regulation of Gli-1 inhibits hepatocellular carcinoma cell migration and invasion. Molecular and cellular biochemistry 43 24792036
2019 A Smo/Gli Multitarget Hedgehog Pathway Inhibitor Impairs Tumor Growth. Cancers 42 31601026
2022 A mineralizing pool of Gli1-expressing progenitors builds the tendon enthesis and demonstrates therapeutic potential. Cell stem cell 41 36459968
2014 Arhgap36-dependent activation of Gli transcription factors. Proceedings of the National Academy of Sciences of the United States of America 40 25024229
2019 Activating CCT2 triggers Gli-1 activation during hypoxic condition in colorectal cancer. Oncogene 39 31462707
2021 Alveolar Bone Marrow Gli1+ Stem Cells Support Implant Osseointegration. Journal of dental research 38 34009063
2013 Nonclassical hedgehog-GLI signaling and its clinical implications. International journal of cancer 38 23929208
2012 Hedgehog/Gli control by ubiquitination/acetylation interplay. Vitamins and hormones 38 22391305
2023 GLI1 Immunohistochemistry Distinguishes Mesenchymal Neoplasms With GLI1 Alterations From Morphologic Mimics. The American journal of surgical pathology 37 36693363
2001 Are keloids really "gli-loids"?: High-level expression of gli-1 oncogene in keloids. Journal of the American Academy of Dermatology 37 11606920
2012 Targeting hedgehog-GLI-2 pathway in osteosarcoma. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 36 22968906
2008 Protein kinase Cdelta negatively regulates hedgehog signaling by inhibition of Gli1 activity. The Journal of biological chemistry 36 19015273
2022 GLI1 Gene Alterations in Neoplasms of the Genitourinary and Gynecologic Tract. The American journal of surgical pathology 33 34907995
2008 Primers on molecular pathways GLI: more than just Hedgehog? Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 33 18497536
2018 MEKK2 and MEKK3 suppress Hedgehog pathway-dependent medulloblastoma by inhibiting GLI1 function. Oncogene 31 29662197
2022 GLI1 -Rearranged Enteric Tumor : Expanding the Spectrum of Gastrointestinal Neoplasms With GLI1 Gene Fusions. The American journal of surgical pathology 29 35968961
2004 Gli proteins up-regulate the expression of basonuclin in Basal cell carcinoma. Cancer research 29 15313903
2022 Gli1+-PDL Cells Contribute to Alveolar Bone Homeostasis and Regeneration. Journal of dental research 28 35786034
1999 Gli genes and limb development. Cell and tissue research 28 10199967
2023 Targeting GLI1 and GLI2 with small molecule inhibitors to suppress GLI-dependent transcription and tumor growth. Pharmacological research 27 37473878
2013 Hedgehog and Gli signaling in embryonic mammary gland development. Journal of mammary gland biology and neoplasia 27 23677624
2022 GLI transcriptional repression is inert prior to Hedgehog pathway activation. Nature communications 26 35145123
2022 Gli Phosphorylation Code in Hedgehog Signal Transduction. Frontiers in cell and developmental biology 25 35186941
2022 Response of Gli1+ Suture Stem Cells to Mechanical Force Upon Suture Expansion. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 25 35443291
2020 Up-regulation of GLI1 in vincristine-resistant rhabdomyosarcoma and Ewing sarcoma. BMC cancer 24 32493277
2021 The vital role of Gli1+ mesenchymal stem cells in tissue development and homeostasis. Journal of cellular physiology 23 33533019
2012 Gli protein nuclear localization signal. Vitamins and hormones 23 22391300
2018 A conditionally immortalized Gli1-positive kidney mesenchymal cell line models myofibroblast transition. American journal of physiology. Renal physiology 22 30303712
2020 Gene of the month: GLI-1. Journal of clinical pathology 21 31980562
2019 Unique and overlapping GLI1 and GLI2 transcriptional targets in neoplastic chondrocytes. PloS one 21 30695055
2022 ULK3-dependent activation of GLI1 promotes DNMT3A expression upon autophagy induction. Autophagy 20 35226587
2020 Fine-Tuning of GLI Activity through Arginine Methylation: Its Mechanisms and Function. Cells 20 32859041
2016 GLI1, a master regulator of the hallmark of pancreatic cancer. Pathology international 20 27862693
2020 RAB23 coordinates early osteogenesis by repressing FGF10-pERK1/2 and GLI1. eLife 19 32662771
2019 Regulation of GLI1 by cis DNA elements and epigenetic marks. DNA repair 19 31085420
2022 GLI1 activates pro-fibrotic pathways in myelofibrosis fibrocytes. Cell death & disease 18 35595725
2016 Nek2A/SuFu feedback loop regulates Gli-mediated Hedgehog signaling pathway. International journal of oncology 18 28035348
2023 Gli1 marks a sentinel muscle stem cell population for muscle regeneration. Nature communications 17 37914731
2022 ERK2 MAP kinase regulates SUFU binding by multisite phosphorylation of GLI1. Life science alliance 17 35831023
2020 Hedgehog pathway activation in oral squamous cell carcinoma: cancer-associated fibroblasts exhibit nuclear GLI-1 localization. Journal of molecular histology 17 33000351
2018 Clinical Significance of Gli-1 And Caveolin-1 Expression in the Human Small Cell Lung Cancer. Asian Pacific journal of cancer prevention : APJCP 17 29479989
2022 Identification of a rare Gli1+ progenitor cell population contributing to liver regeneration during chronic injury. Cell discovery 16 36316325
2023 GLI1-Altered Mesenchymal Tumors. Surgical pathology clinics 15 38278602
2022 Gli1+ Osteogenic Progenitors Contribute to Condylar Development and Fracture Repair. Frontiers in cell and developmental biology 15 35330911
2021 Hedgehog/GLI1 signaling pathway regulates the resistance to cisplatin in human osteosarcoma. Journal of Cancer 15 34659557
2020 Gli1 interacts with YAP1 to promote tumorigenesis in esophageal squamous cell carcinoma. Journal of cellular physiology 14 31957872
2019 Regulation of Survivin Isoform Expression by GLI Proteins in Ovarian Cancer. Cells 14 30736319
2021 Gli1 Regulates the Postnatal Acquisition of Peripheral Nerve Architecture. The Journal of neuroscience : the official journal of the Society for Neuroscience 13 34772739
2021 Advances in glioma-associated oncogene (GLI) inhibitors for cancer therapy. Investigational new drugs 13 34837604
2019 The Plk1 kinase negatively regulates the Hedgehog signaling pathway by phosphorylating Gli1. Journal of cell science 13 30578313
2024 Gli1+ Periodontal Mesenchymal Stem Cells in Periodontitis. Journal of dental research 12 38284236
2024 β-catenin Orchestrates Gli1+ Cell Fate in Condylar Development and TMJOA. Journal of dental research 12 39400124
2020 Gli1 regulates stemness characteristics in gastric adenocarcinoma. Diagnostic pathology 12 32430068
2018 Trichostatin A promotes GLI1 degradation and P21 expression in multiple myeloma cells. Cancer management and research 12 30214285

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