GLI1

Source: Wikipedia, the free encyclopedia.
GLI1
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl

ENSG00000111087

ENSMUSG00000025407

UniProt

P08151

P47806

RefSeq (mRNA)

NM_001160045
NM_001167609
NM_005269

NM_010296

RefSeq (protein)

NP_001153517
NP_001161081
NP_005260

NP_034426

Location (UCSC)Chr 12: 57.46 – 57.47 MbChr 10: 127.17 – 127.18 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Zinc finger protein GLI1 also known as glioma-associated oncogene is a protein that in humans is encoded by the GLI1 gene. It was originally isolated from human glioblastoma cells.[5]

Function

The Gli proteins are the effectors of

Sonic hedgehog into different cell fates along the dorsoventral axis.[7]

The Gli transcription factors activate/inhibit transcription by binding to Gli responsive genes and by interacting with the transcription complex. The Gli transcription factors have DNA binding zinc finger domains which bind to consensus sequences on their target genes to initiate or suppress transcription.[8] Yoon[9] showed that mutating the Gli zinc finger domain inhibited the proteins effect proving its role as a transcription factor. Gli proteins have an 18-amino acid region highly similar to the α-helical herpes simplex viral protein 16 activation domain. This domain contains a consensus recognition element for the human TFIID TATA box-binding protein associated factor TAFII31.[9] Other proteins such as Missing in Metastasis (MIM/BEG4) have been shown to potentiate the effects of the Gli transcription factors on target gene transcription. Gli and MIM have been shown to act synergistically to induce epidermal growth and MIM + Gli1 overexpressing grafts show similar growth patterns to Shh grafts.[10]

Gli family

There are three members of the family; Gli1,

transcription factors mediating the Hh pathway. The GLI1, GLI2, and GLI3 genes encode transcription factors which all contain conserved tandem C2-H2 zinc finger domains and a consensus histidine/cysteine linker sequence between zinc fingers. This Gli motif is related to those of Kruppel which is a Drosophila segmentation gene of the gap class.[11] In transgenic mice, mutant Gli1 lacking the zinc fingers does not induce Sonic Hedgehog (Shh) targets.[12] The conserved stretch of 9 amino acids connects the C-terminal histidine of one finger to the N-terminal cysteine of the next. The GLI consensus finger amino acid sequence is [Y/F]JXCX3GCX3[F/Y]X5LX2HX4H[T/S]GEKP.[11] The Gli1 and Gli2 protein zinc finger DNA
binding domain have been shown to bind to the DNA consensus GLI binding site GACCACCCA. [13]

Gli Proteins transcriptional regulation is tissue specific for many targets. For example, Gli1 in primary keratinocytes upregulates FOXM1[14] whereas in mesenchymal C3H10T1/2 cells it has been shown to upregulate platelet-derived growth factor receptor PDGFRa.[15]

Human Gli1 encodes a transcription activator involved in development that is a known

chromosomes.[17] This may negatively regulate transcription indicating Gli1 could act as transcriptional inhibitor as well as an activator.[18] The human GLI1 promoter region is regulated by a 1.4 kb 5’ region including a 5’ flanking sequence, an untranslated exon and 425bp of the first intron. Numerous proteins such as Sp1, USF1, USF2, and Twist are also involved in Gli1 promoter regulation.[19][20][21] During mouse embryo development Gli1 expression can be detected in the gut mesoderm, ventral neural tube, ependymal layer of the spinal cord, forebrain, midbrain, cerebellum, and in sites of endochondral bone formation.[22][23][24] Some of the downstream gene targets of human Gli1 include regulators of the cell cycle and apoptosis such as cyclin D2 and plakoglobin respectively.[25] Gli1 also upregulates FoxM1 in BCC.[14] Gli1 expression can also mimic Shh expression in certain cell types.[26]

Isolation

GLI1 was originally isolated from a glioma

Basal cell carcinoma (BCC).[27]
DNA copy-number alterations that contribute to increased conversion of the oncogenes Gli1–3 into transcriptional activators by the Hedgehog signaling pathway are included in a genome-wide pattern, which was found to be correlated with an astrocytoma patient’s outcome.[28] Shh and the Gli genes are normally expressed in
tumours that express endogenous Gli1. This suggests that overexpressed Gli1 alone is probably sufficient for tumour development[30][31] Mutations leading to the expression of Gli1 in basal cells are thus predicted to induce BCC formation.[26]

Interactions

GLI1 has been shown to

interact
with:

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000111087 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025407 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. PMID 3563490
    .
  6. PMID 10375510
    .
  7. PMID 25398016
    .
  8. PMID 9118802
    .
  9. ^
    PMID 9524201
    .
  10. PMID 15545630
    .
  11. ^
    PMID 2850480
    .
  12. PMID 10725236
    .
  13. PMID 2105456
    .
  14. ^
    PMID 12183437
    .
  15. ^ Xie J, Aszterbaum M, Zhang X, Bonifas JM, Zachary C, Epstein E, McCormick F (July 2001). "A role of PDGFRalpha in basal cell carcinoma proliferation". Proc Natl Acad Sci U S A. 98 (16): 9255–9.
    PMID 11481486
    .
  16. PMID 3563490
    .
  17. PMID 11960000
    .
  18. PMID 12897799
    .
  19. S2CID 12132097
    .
  20. PMID 9299114
    .
  21. PMID 9168805
    .
  22. PMID 8150204
    .
  23. S2CID 8951322
    .
  24. S2CID 12373898
    .
  25. PMID 11719506
    .
  26. ^
    S2CID 4424572
    .
  27. PMID 22114144
    .
  28. PMID 27798635
    .
  29. S2CID 4424572
    . Erratum in: Nature 1997 December 4;390(6659):536.
  30. ^
    PMID 10725363
    .
  31. PMID 25253693
    .
  32. PMID 11960000
    .
  33. S2CID 31424234
    .
  34. PMID 10564661
    .
  35. S2CID 6907964
    .
  36. PMID 12426310
    .
  37. PMID 11238441
    .

External links
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