GLI ACTIVATES TRANSCRIPTION THROUGH A HERPES-SIMPLEX VIRAL PROTEIN 16-LIKE ACTIVATION DOMAIN

Three proteins have been identified in mammals, GLI, GLI2, and GLI3, w hich share a highly conserved zinc finger domain with Drosophila Cubit us interruptus and are believed to function as transcription factors i n the vertebrate Sonic hedgehog-Patched signaling pathway, To understa nd the role GLI plays in the Sonic hedgehog-Patched pathway and mechan isms of GLI-induced transcriptional regulation, we have characterized its transcriptional regulatory properties and contributions of specifi c domains to transcriptional regulation, We have demonstrated that GLI activates expression of reporter constructs in HeLa cells in a concen tration-dependent manner through the GLI consensus binding motif and t hat a GAL4 binding domain-GLI fusion protein activates reporter expres sion through the GAIA DNA binding site, GLI-induced transcriptional ac tivation requires the carboxyl-terminal amino acids 1020-1091, which i ncludes an 18-amino acid region highly similar to the alpha-helical he rpes simplex viral protein 16 activation domain, including the consens us recognition element for the human TFIID TATA box-binding protein-as sociated factor TAF(II)31 and conservation of all three amino acid res idues believed to contact directly chemically complementary residues i n TAF(II)31. The presence of this region in the GLI activation domain provides a mechanism for GLI-induced transcriptional regulation.