GLI2
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Location (UCSC) | Chr 2: 120.74 – 120.99 Mb | Chr 1: 118.76 – 118.98 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
Zinc finger protein GLI2 also known as GLI family zinc finger 2 is a protein that in humans is encoded by the GLI2 gene.[5] The protein encoded by this gene is a transcription factor.[6]
GLI2 belongs to the C2H2-type zinc finger protein subclass of the Gli family. Members of this subclass are characterized as transcription factors which bind DNA through zinc finger motifs. These motifs contain conserved H-C links. Gli family zinc finger proteins are mediators of Sonic hedgehog (Shh) signaling and they are implicated as potent oncogenes in the embryonal carcinoma cell. The protein encoded by this gene localizes to the cytoplasm and activates patched Drosophila homolog (PTCH) gene expression. It is also thought to play a role during embryogenesis.[7]
Isoforms
There are four isoforms: Gli2 alpha, beta, gamma and delta.[8]
Structure
, suggesting that it may lack repressor function.Function
Gli2 affects
It has been shown in mouse models that Gli1 can compensate for knocked out Gli2 function when expressed from the Gli2
Transgenic double
Transgenic Gli1-/- and Gli2-/- mice have a similar phenotype to transgenic Gli1 gain of function mice. This phenotype includes failure to thrive, early death, and a distended gut although no
Transgenic mice over-expressing the transcription factor Gli2 under the K5 promoter in
Of the four Gli2 isoforms the expression of Gli2beta mRNA was increased the most in BCCs. Gli2beta is an isoform spliced at the first splicing site which contains a repression domain and consists of an intact activation domain. Overexpression of this Gli2 splice variant may lead to the upregulation of the Shh signalling pathway, thereby inducing BCCs.[8]
Clinical significance
Mutations of the GLI2 gene are associated with several phenotypes including Greig cephalopolysyndactyly syndrome, Pallister–Hall syndrome, preaxial polydactyly type IV, postaxial polydactyly types A1 and B.[7]
In human keratinocytes Gli2 activation upregulates a number of genes involved in cell cycle progression including E2F1, CCND1, CDC2 and CDC45L. Gli2 is able to induce G1–S phase progression in contact-inhibited keratinocytes which may drive tumour development.[15]
Although both Gli1 and Gl12 have been implicated it is unclear whether one or both are needed for carcinogenesis. However, due to feed back loops, one may directly or indirectly induce the other.
Cis-regulatory catalog of GLI2
Minhas et al. 2015 have recently elucidated a subset of cis-regulatory elements controlling GLI2 expression. They have shown that conserved non-coding elements (CNEs) from the intron of GLI2 gene act as tissue-specific enhancers and reporter gene expression induced by these elements correlates with previously reported endogenous gli2 expression in zebrafish. The regulatory activities of these elements are observed in several embryonic domains, including neural tube and pectoral fin.[23]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000074047 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000048402 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 9557682.
- PMID 2850480.
- ^ a b "Entrez Gene: GLI family zinc finger 2".
- ^ S2CID 23655947.
- PMID 10433919.
- PMID 11003839.
- ^ PMID 15520176.
- PMID 30086335.
- PMID 22309705.
- ^ S2CID 195211836.
- ^ S2CID 23702873.
- S2CID 10102370.
- PMID 10725236.
- PMID 9006072.
- PMID 9655803.
- PMID 9440116.
- PMID 12235001.
- PMID 12648487.
- S2CID 6566275.
External links
- Gli2+protein at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- GLI2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.