Increased proteolytic processing of full-length Gli2 transcription factor reduces the hedgehog pathway activity in vivo
Kruppel-Like Transcription Factors
Protein Processing, Post-Translational
The proteolytic processing of Gli2 and Gli3 full-length transcription factors into repressors is a key step of the regulation in Hedgehog (Hh) signaling. The differential Gli2 and Gli3 processing is controlled by the processing determinant domain or PDD, but its significance is not clear. We generated a Gli2 mutant allele, Gli2(3PDD) , in which the Gli3PDD substitutes for the Gli2PDD. As expected, Gli2(3PDD) is processed more efficiently and at a different position as compared to Gli2, indicating that PDD also determines the extent and site of Gli2 and Gli3 processing in vivo. The increase in levels of the Gli2 repressor in Gli2(3PDD) mutant reduces the Hh pathway activity. Gli2(3PDD) processing is still regulated by Hh signaling. These results indicate that the proper balance between the Gli2 full-length activator and repressor is essential for Hh signaling.