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FLASH GENE
Symbol GLI1 contributors: mct - updated : 21-10-2016
HGNC name GLI family zinc finger 1
HGNC id 4317
Location 12q13.3      Physical location : 57.853.917 - 57.866.045
Synonym name
  • glioma-associated oncogene homolog 1 (zinc finger protein)
  • oncogene GLI
  • glioma-associated oncogene family zinc finger 1
  • Synonym symbol(s) GLI
    DNA
    TYPE functioning gene
    STRUCTURE 12.13 kb     12 Exon(s)
    regulatory sequence Promoter
    text structure activated by EWS-FLI1
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 - 3618 117.7 1106 - 1987 3563490
  • isoform 1
  • up-regulated not only by HH signaling but also additional factors play a role in balancing their expression levels
  • 10 - 3414 104.5 978 - 2008 18378682
  • N-terminal truncated protein isoform (skip exons 2 and 3)
  • Gli1 Delta N, isoform 2
  • up-regulated not only by HH signaling but also additional factors play a role in balancing their expression levels
  • 11 - 3483 - 1065 . frequently expressed in human breast cancer cell lines, but is undetectable in normal breast tissues 2012 21666712
  • also called isoform 3 or tGli1
  • in-frame deletion of 41 codons spanning the entire exon 3 and part of exon 4
  • has gained the ability to promote glioblastoma migration and invasion via its gain-of-function transcriptional activity
  • binds to and enhances VEGFA gene promoter, leading to its upregulation . gain-of-function GLI1 transcription factor and a novel mediator of the behavior of clinically more aggressive breast cancer
  • EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouthtongue  highly
    Reproductivefemale systemoviduct   
     female systemuterus   
     male systemtestis   
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  highly
    Muscularsmoothuterusmyometrium 
    Muscularstriatumskeletal highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • zinc finger protein
  • HOMOLOGY
    interspecies homolog to Drosophila segment polarity gene Cubitus interruptus
    homolog to rattus Gli1 (86.2pc)
    homolog to murine Gli1 (86.1pc)
    intraspecies homolog to glioma-associated oncogene homolog
    Homologene
    FAMILY
  • GLI C2H2-type zinc-finger protein family
  • Krüppel family of zinc finger proteins
  • CATEGORY transcription factor , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus
    text
  • could be colocalized in the nucleus with AR in the absence of appropriate ligands
  • nuclear translocation of cytosolic GLI1 protein was inhibited by VHL via protein-protein interaction
  • basic FUNCTION
  • acting as an activator in sonic hedgehog signaling after induction by binding of GLI3 to GLI1 promoter (activator of PTCH1, BMP4 and BMP7)
  • involved in lymphomagenesis (diffuse large B cell lymphoma)and in basal cell carcinoma
  • transcription factor, which acts as a terminal effector of the HH signaling pathway, in addition to being a target gene
  • play an important role in the invasiveness of pancreatic cancer cells through the regulation of MMP9 expression
  • mediates pancreatic ductal adenocarcinoma cell survival and transformation
  • may regulate the transcription of specific genes during normal development
  • may play a role in craniofacial development and digital development, as well as development of the central nervous system and gastrointestinal tract
  • regulating stem cell proliferation
  • play a central role in sonic hedgehog signaling in prostate cancer, can act as a co-repressor to substantially block androgen receptor-mediated transactivation
  • potentially act as a co-repressor that substantially blocked both ligand-dependent and -independent transactivation of AR
  • important positive regulator of epithelial differentiation, and they offer an explanation for how decreased levels of GLI1 are likely to contribute to the highly metastatic phenotype of pancreatic ductal adenocarcinoma
  • GLI1 itself can induce early osteoblast differentiation, at least to some extent, in a RUNX2-independent manner
  • acts in the last known step of the Hedgehog signaling
  • novel role for GLI1 in carcinogenesis acting as a downstream effector of oncogenic KRAS in the tumor microenvironment
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    GLI1 and PTCH1 are both components and transcriptional targets of the SHH pathway
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting in a positive feedback loop with SHH in mouse limb development and with DHH and IHH in carcinogenesis
  • PDGFRA
  • PTCH
  • GLI1-GLI2 feedback loop in hedgehog-mediated epidermal cell proliferation, binded by its GLI-binding consensus sequence in the promoter (GLI2 directly activates GLI1)
  • interacting with STK36
  • direct transcriptional target of EWS-FLI1 and may have a potential role for GLI1 in Ewing sarcoma family of tumors tumorigenesis
  • interacting with SUFU and SPOP (SUFU regulates GLI protein levels by antagonizing the activity of SPOP, a conserved GLI-degrading factor)
  • PIAS1-dependent SUMOylation influences GLI1, GLI2, GLI3 protein activity and thereby identifies SUMOylation as a post-translational mechanism that regulates the hedgehog signaling pathway
  • interacts with SMARCB1 (localizes to GLI1-regulated promoters and loss of SMARCB1 leads to activation of the HH-GLI pathway)
  • GNB2L1 suppresses FEM1B pro-apoptotic activity in cancer cells and promote activation of GLI1 activity in cancer cells
  • play a central role in SHH signaling in prostate cancer, and can act as a co-repressor to substantially block AR-mediated transactivation, at least in part, by directly interacting with AR
  • directly regulated the transcription of CDH1, a key determinant of epithelial tissue organization
  • potentially, upon Hedgehog input, GLI1 functions collectively with GLI2 and GLI3 in osteogenesis
  • enhances the function of GLI1 by increasing its transcriptional activity, nuclear localization and protein stability, but not of GLI2 nor GLI3
  • regulatory loop between FERMT2 and GLI1, an effector of Hedgehog signaling pathway (FERMT2 is transcriptionally downregulated via GLI1 occupancy on the FERMT2 promoter)
  • overexpression of VHL may antagonize Hedgehog-GLI1 activation at the post-translational level in Hedgehog pathway-induced cancers
  • key role for GLI1 in maintaining the levels of activated STAT3 through the modulation of IL6 signaling
  • FEM1B interacts with GLI1 within cells, and directly binds GLI1 (promotes ubiquitylation of GLI1, suppresses transcriptional activation by GLI1, and attenuates an oncogenic GLI1 autoregulatory loop in cancer cells)
  • GLI1 and GLI2 activated the expression of a basic helix-loop-helix type suppressor BHLHE41 through a GLI-binding site in the promoter
  • PKD1L1-PKD2L1 acts as a ciliary calcium channel controlling ciliary calcium concentration and thereby modifying SMO-activated GLI2 translocation and GLI1 expression
  • connection between SHH-GLI1 signaling and S100A4 regulation, which imply that S100A4 might be one of the key factors in EMT mediated by SHH-GLI1 signaling in pancreatic cancer (pMID: 25072505)
  • GLI1, GLI2, GLI3 interacts synergistically with KIFAP3 and KIF3A
  • GLI1 and GLI2 directly bind to the promoter regions of NEK2 gene and induced its transcription
  • cell & other
    REGULATION
    activated by interaction with STK36 and translocated to the nucleus
    SMO
    the sonic hedgehog signal transduction cascade
    inhibited by RAB23 that directly associates with SUFU and inhibits GLI1 function in a SUFU-dependent manner
    repressed by NR0B2, inhibiting its nuclear localization
    Other activity and nuclear localization is negatively regulated by TP53 in an inhibitory loop
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    deregulating the SHH pathway and associated with basal cell carcinoma
    tumoral fusion      
    with ACTB in through the translocation t(7;12)(p22;q13), in pericytoma
    tumoral somatic mutation amplification    
    amplified in glioblastoma
    tumoral     --over  
    overexpression of MAP3K10 resulted in upregulation of GLI1 and GLI2 in pancreatic ductal adenocarcinoma (PDAC) cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    development of GLI inhibitors, novel agents could be used to treat cancers including Ewing sarcoma family of tumors, which have activation of the pathway at the level of GLI
    cancerreproductiveprostate
    manipulating the SHH-GLI pathway, in combination with androgen ablation may prove to be useful for treatment of androgen-independent prostatic tumors
    cancerreproductiveprostate
    targeting the FERMT2-GLI1 feedback loop may facilitate the killing of prostate cancer cells
    ANIMAL & CELL MODELS
  • inhibition of Shh signaling pathway exacerbated rat ischemic damage caused by permanent middle cerebral artery occlusion, which may be correlated with down-regulated expression of Gli1, Ptch1 and Sod1