GLI1 (glioma-associated oncogene homolog 1)

2005-03-01   Anna Dahlén , Fredrik Mertens , Nils Mandahl , Ioannis Panagopoulos 

Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden

Identity

HGNC
LOCATION
12q13.3
LOCUSID
ALIAS
GLI,PAPA8,PPD1
FUSION GENES

DNA/RNA

Atlas Image
Genomic organization of the GLI1 gene.

Description

12 exons, spans approximately 12 kb of genomic DNA in the centromere-to-telomere orientation. The translation initiation codon is located to exon 2, and the stop codon to exon 12.

Transcription

mRNA of 3.6 kb

Proteins

Description

The open reading frame encodes a 1106 amino acid protein, with an estimated molecular weight of approximately 118 kDa. The protein contains five DNA-binding zinc fingers between amino acids 235 and 393 (encoded by exons 7-10), and a transactivating domain constituted by amino acids 1020-1091 (encoded by exon 12).

Expression

GLI proteins function as direct effectors of sonic hedgehog-signaling during embryogenesis. GLI1 (also GLI2 and GLI3) are therefore likely to be involved in the tissue-specific proliferation of the central nervous system, the zones of polarizing activity in the developing limb, and of the gut. In the adult human, GLI1 expression has been demonstrated in the testes, myometrium and Fallopian tubes.

Localisation

Nuclear. Might be fluctuating between the cytoplasm and the nucleus.

Function

DNA-binding transcription factor

Mutations

Germinal

An abnormal activity of GLI, caused by mutations affecting upstream components of the sonic hedgehog-signaling pathway (sonic hedgehog, patched or smoothened) are associated with developmental disorders.

Somatic

Various tumors of mesenchymal and lymphocytic origin.

Implicated in

Note
Rearrangement and fusion of the GLI1 gene.
Prognosis
Benign or low-malignant
Cytogenetics
t(7;12)(p22;q13)
Hybrid gene
ACTB-GLI1 fusion gene. The breakpoints reported so far have been located to introns 1, 2 or 3 within the ACTB gene, and to introns 5 or 6 or to exon 7 within the GLI1 gene. Reciprocal GLI1-ACTB gene fusions have also been detected. The breakpoints have been located to introns 5 or 7 within the GLI1 gene, and to intron 3 of the ACTB gene.
Atlas Image
Representative G-banded partial karyotype of the t(7;12)(p22;q13).
Fusion protein
The ACTB-GLI1 fusion protein contains the N-terminal of ACTB and the C-terminal of GLI1, including the DNA-binding zinc finger motifs (encoded by exons 7-10) and transactivating motifs (exon 12).
Oncogenesis
It is suggested that the strong ACTB promoter causes an overexpression of GLI1 sequences important for transcriptional activation of downstream target genes, akin to the oncogenic mechanisms of the COL1A1-PDGFB fusion gene detected in dermatofibrosarcoma protuberans.
Note
Amplification of the GLI1 gene
Disease
Glioma, B-cell lymphoma, sarcoma
Prognosis
Depends on tumor type
Oncogenesis
Overexpression of GLI1 sequences. Might be of prognostic importance.

Bibliography

Pubmed IDLast YearTitleAuthors
24970591989In situ hybridization localizes the human putative oncogene GLI to chromosome subbands 12q13.3-14.1.Arheden K et al
155555712004Molecular genetic characterization of the genomic ACTB-GLI fusion in pericytoma with t(7;12).Dahlén A et al
86411331996Assignment of the gene encoding human Krüppel-related zinc finger protein 4 (GLI4) to 8q24.3 by fluorescent in situ hybridization.Kas K et al
21054561990The GLI gene encodes a nuclear protein which binds specific sequences in the human genome.Kinzler KW et al
95242011998Characterization of the promoter region and genomic organization of GLI, a member of the Sonic hedgehog-Patched signaling pathway.Liu CZ et al
88124451996Assignment of the human GLI2 gene to 2q14 by fluorescence in situ hybridization.Matsumoto N et al
104413311999Expression of the Sonic hedgehog (SHH ) gene during early human development and phenotypic expression of new mutations causing holoprosencephaly.Odent S et al
27663051989Amplification of the gli gene in childhood sarcomas.Roberts WM et al
21189971990GLI3 encodes a 190-kilodalton protein with multiple regions of GLI similarity.Ruppert JM et al
89881771997Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell fibroblastoma.Simon MP et al
110015842000The sonic hedgehog-patched-gli pathway in human development and disease.Villavicencio EH et al
92501471997High-level DNA amplifications are common genetic aberrations in B-cell neoplasms.Werner CA et al

Other Information

Locus ID:

NCBI: 2735
MIM: 165220
HGNC: 4317
Ensembl: ENSG00000111087

Variants:

dbSNP: 2735
ClinVar: 2735
TCGA: ENSG00000111087
COSMIC: GLI1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000111087ENST00000228682P08151
ENSG00000111087ENST00000528432E9PQQ1
ENSG00000111087ENST00000528467P08151
ENSG00000111087ENST00000532291E9PIB9
ENSG00000111087ENST00000543426P08151
ENSG00000111087ENST00000546141P08151

Expression (GTEx)

0
5
10
15
20
25
30
35
40
45
50

Pathways

PathwaySourceExternal ID
Hedgehog signaling pathwayKEGGko04340
Basal cell carcinomaKEGGko05217
Hedgehog signaling pathwayKEGGhsa04340
Pathways in cancerKEGGhsa05200
Basal cell carcinomaKEGGhsa05217
cAMP signaling pathwayKEGGhsa04024
cAMP signaling pathwayKEGGko04024
Hedgehog signalingKEGGhsa_M00678
Hedgehog signalingKEGGM00678
Signal TransductionREACTOMER-HSA-162582
Signaling by HedgehogREACTOMER-HSA-5358351
Hedgehog 'off' stateREACTOMER-HSA-5610787
Degradation of GLI1 by the proteasomeREACTOMER-HSA-5610780
Hedgehog 'on' stateREACTOMER-HSA-5632684
GLI proteins bind promoters of Hh responsive genes to promote transcriptionREACTOMER-HSA-5635851

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
171963912007HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity.375
176280162007Cyclopamine-mediated hedgehog pathway inhibition depletes stem-like cancer cells in glioblastoma.222
173924272007Melanomas require HEDGEHOG-GLI signaling regulated by interactions between GLI1 and the RAS-MEK/AKT pathways.213
200497372009Human colon cancer epithelial cells harbour active HEDGEHOG-GLI signalling that is essential for tumour growth, recurrence, metastasis and stem cell survival and expansion.182
153142192004Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling.172
176389102007Induction of sonic hedgehog mediators by transforming growth factor-beta: Smad3-dependent activation of Gli2 and Gli1 expression in vitro and in vivo.158
205818022010NANOG regulates glioma stem cells and is essential in vivo acting in a cross-functional network with GLI1 and p53.123
171150282006Numb is a suppressor of Hedgehog signalling and targets Gli1 for Itch-dependent ubiquitination.116
200834812010Context-dependent regulation of the GLI code in cancer by HEDGEHOG and non-HEDGEHOG signals.110
192141862009A GLI1-p53 inhibitory loop controls neural stem cell and tumour cell numbers.96

Citation

Anna Dahlén ; Fredrik Mertens ; Nils Mandahl ; Ioannis Panagopoulos

GLI1 (glioma-associated oncogene homolog 1)

Atlas Genet Cytogenet Oncol Haematol. 2005-03-01

Online version: http://atlasgeneticsoncology.org/gene/310/gli1