title: Increased proteolytic processing of full-length Gli2 transcription factor reduces the hedgehog pathway activity in vivo.
abstract: 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.
authors.affiliation: Institute of Developmental Immunology, College of Life Science, Shandong University, Jinan, P. R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Chengbing
authors.initials: C
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Pan
authors.forename: Zengliang
authors.initials: Z
authors.lastname: Bai
authors.forename: Baolin
authors.initials: B
authors.lastname: Wang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000378:metabolism / Q000502:physiology*; D051741:Kruppel-Like Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D000075746:Zinc Finger Protein Gli2
chemical_list: C000618551:Gli2 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D020033:Protein Isoforms; D014157:Transcription Factors; D000075746:Zinc Finger Protein Gli2