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Concept
GLI2
Résumé
Zinc finger protein GLI2 also known as GLI family zinc finger 2 is a protein that in humans is encoded by the GLI2 gene. The protein encoded by this gene is a transcription factor.
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.
There are four isoforms: Gli2 alpha, beta, gamma and delta.
C-terminal activator and N-terminal repressor regions have been identified in both Gli2 and Gli3. However, the N-terminal part of human Gli2 is much smaller than its mouse or frog homologs, suggesting that it may lack repressor function.
Gli2 affects ventroposterior mesodermal development by regulating at least three different genes; Wnt genes involved in morphogenesis, Brachyury genes involved in tissue specification and Xhox3 genes involved in positional information. The anti-apoptotic protein BCL-2 is up regulated by Gli2 and, to a lesser extent, Gli1 – but not Gli3, which may lead to carcinogenesis. Additionally, in the amphibian model organism Xenopus laevis, it has been shown that Gli2 plays a key role in the induction, specification, migration and differentiation of the neural crest. In this context, Gli2 is responding to the Indian Hedgehog signaling pathway.
It has been shown in mouse models that Gli1 can compensate for knocked out Gli2 function when expressed from the Gli2 locus. This suggests that in mouse embryogenesis, Gli1 and Gli2 regulate a similar set of target genes. Mutations do develop later in development suggesting Gli1/Gli2 transcriptional regulation is context dependent.
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