Transcriptional activity of GLI1 is negatively regulated by protein kinase A

The transcription factor GLI1 is one of three vertebrate members of the GLI family, which is characterized by a highly conserved DNA-binding domain of five zinc fingers. We have analyzed whether human GLI1 is a target of PKA regulation. It was found that PKA inhibits GLI1 transcriptional activity. However, no evidence for proteolytic processing or for alteration in the subcellular distribution of GLI1 was obtained. The responsive PKA site (aa333-336) was localized to the second zinc finger of GLI1. Mutation of Ser336 revealed that PKA could also stimulate GLI1 transcriptional activity. Thus, our data demonstrate both negative and positive regulation of human GLI1 by PKA.