Zinc finger protein GLI3 is aprotein that in humans is encoded by theGLI3gene.[5][6]
This gene encodes aprotein that belongs to the C2H2-typezinc finger proteins subclass of the Gli family. They are characterized as DNA-bindingtranscription factors and are mediators ofSonic hedgehog (Shh)signaling. The protein encoded by this gene localizes in thecytoplasm and activates patched Drosophila homolog (PTCH1) gene expression. It is also thought to play a role duringembryogenesis.[6]
Gli3 is a knowntranscriptionalrepressor but may also have a positive transcriptional function.[7][8] Gli3 repressesdHand andGremlin, which are involved in developingdigits.[9] There is evidence thatShh-controlled processing (e.g., cleavage) regulates transcriptional activity of Gli3 similarly to that ofCi.[8] Gli3 mutant mice have many abnormalities includingCNS andlung defects and limbpolydactyly.[10][11][12][13][14] In the developing mouse limb bud, Gli3 derepression predominantly regulates Shh target genes.[15]
Mutations in this gene have been associated with several diseases, includingGreig cephalopolysyndactyly syndrome,Pallister–Hall syndrome, preaxialpolydactyly type IV, and postaxial polydactyly types A1 and B.[6] 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 anastrocytoma patient's outcome.[16][17]
The independentoverexpressionGli1 andGli2 inmice models to lead to formation ofbasal cell carcinoma (BCC). Gli1 knockout is shown to lead to similarembryonic malformations as Gli1 overexpressions but not the formation of BCCs. Overexpression of Gli3 in transgenic mice and frogs does not lead to the development of BCC-like tumors and is not thought to play a role intumor BCC formation.[19]
Gli1 and Gli2 overexpression leads to BCC formation in mouse models and a one step model for tumour formation has been suggested in both cases. This also indicates that Gli1 and/or Gli2 overexpression is vital in BCC formation. Co-overexpression of Gli1 with Gli2 and Gli2 with Gli3 leads to transgenic mice malformations and death, respectively, but not the formation of BCC. This suggests that overexpression of more than one Gliprotein is not necessary for BCC formation.
^Franz T (1994). "Extra-toes (Xt) homozygous mutant mice demonstrate a role for the Gli-3 gene in the development of the forebrain".Acta Anatomica.150 (1):38–44.doi:10.1159/000147600.PMID7976186.
^Grove EA, Tole S, Limon J, Yip L, Ragsdale CW (June 1998). "The hem of the embryonic cerebral cortex is defined by the expression of multiple Wnt genes and is compromised in Gli3-deficient mice".Development.125 (12):2315–25.doi:10.1242/dev.125.12.2315.PMID9584130.
^Hui CC, Joyner AL (March 1993). "A mouse model of greig cephalopolysyndactyly syndrome: the extra-toesJ mutation contains an intragenic deletion of the Gli3 gene".Nature Genetics.3 (3):241–6.doi:10.1038/ng0393-241.PMID8387379.S2CID345712.
^Schimmang T, Lemaistre M, Vortkamp A, Rüther U (November 1992). "Expression of the zinc finger gene Gli3 is affected in the morphogenetic mouse mutant extra-toes (Xt)".Development.116 (3):799–804.doi:10.1242/dev.116.3.799.PMID1289066.
^Dahmane N, Lee J, Robins P, Heller P, Ruiz i Altaba A (October 1997). "Activation of the transcription factor Gli1 and the Sonic hedgehog signalling pathway in skin tumours".Nature.389 (6653):876–81.Bibcode:1997Natur.389..876D.doi:10.1038/39918.PMID9349822.S2CID4424572.
