GLI3

Zinc finger protein GLI3 is a is_associated_with::protein that in humans is encoded by the GLI3 is_associated_with::gene.

This gene encodes a is_associated_with::protein that belongs to the C2H2-type is_associated_with::zinc finger proteins subclass of the Gli family. They are characterized as DNA-binding is_associated_with::transcription factors and are mediators of is_associated_with::Sonic hedgehog (Shh) signaling. The protein encoded by this gene localizes in the is_associated_with::cytoplasm and activates patched Drosophila homolog (is_associated_with::PTCH1) gene expression. It is also thought to play a role during is_associated_with::embryogenesis.

Role in development
Gli3 is a known transcriptional is_associated_with::repressor but may also have a positive transcriptional function. Gli3 represses dHand and Gremlin, which are involved in developing digits. There is evidence that Shh-controlled processing (e.g., cleavage) regulates transcriptional activity of Gli3 similarly to that of CI. Gli3 mutant mice have many abnormalities including CNS and is_associated_with::lung defects and limb is_associated_with::polydactyly.

Disease association
Mutations in this gene have been associated with several diseases, including Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, preaxial polydactyly type IV, and postaxial polydactyly types A1 and B.

There is evidence that the autosomal dominant disorder is_associated_with::Greig cephalopolysyndactyly syndrome (GCPS) that affects limb and craniofacial development in is_associated_with::humans is caused by a translocations within the GLI3 gene.

Interactions with Gli1 and Gli2
The independent is_associated_with::overexpression is_associated_with::Gli1 and is_associated_with::Gli2 in is_associated_with::mice models to lead to formation of is_associated_with::basal cell carcinoma (BCC). Gli1 knockout is shown to lead to similar is_associated_with::embryonic 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 in is_associated_with::tumor BCC formation.

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 Gli is_associated_with::protein is not necessary for BCC formation.

Interactions
GLI3 has been shown to interact with CREBBP is_associated_with::SUFU, is_associated_with::ZIC1, and is_associated_with::ZIC2.