Research Of GRIP1Modulates Hedgehog/Gli1Signaling Pathway

The Hedgehog (HH) pathway is a relatively conserved signaling pathway necessary for embryonic development. There are three members of the Gli protein family. Glil is the most important transcription factor in the HH signaling pathway.GR3P1(Glucocorticoid receptor interacting protein1) is one of the members of Steroid receptor co-activator (SRC) protein family, which serve as transcriptional co-activators for nuclear receptors and certain other transcription factors.The focal point of our research is GRIP1of SRC family could enhance the transcriptional activity of Glil through luciferase reporter gene assays, and its mechanism.First, we found that only GRIP1of SRC family could enhance the transcriptional activity of Gli1through luciferase reporter gene assays in different cell lines. We also found residues1011-1464of GRIP1residues1011-1464of GRIP1enhance the transcriptional activity of Gli1.Furthermore we proposed that this interaction may enhance the transcriptional activity of Gli1via direct interaction between GRIP1and Gli1. Through mammalian two-hybrid analysis and immunofluorescence assays we next demonstrated that GRIP1and Gli1physically interacted with each other.Last investigation showed that the interaction involved residues1011-1464of GRIP1and407-1020amino acids of Glil through mammalian two-hybrid analysis and Immunoprecipitation assays. Residues1011-1464of GRIP1are known to contain the two transcriptional activation domains of GRIP1.