Transcriptional activity of GLI1 is negatively regulated by protein kinaseA

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. H owever, no evidence for proteolytic processing or for alteration in the sub cellular distribution of GLI1 was obtained. The responsive PKA site (aa333- 336) was localized to the second zinc finger of GLI1. Mutation of Ser336 re vealed that PKA could also stimulate GLI1 transcriptional activity. Thus, o ur data demonstrate both negative and positive regulation of human GLI1 by PKA.