Transcription Regulation We have a long-standing interest in of how the product of the pair-rule gene hairy functions during development. Hairy is a transcriptional repressor that belongs to an evolutionary conserved family that includes the E(spl), Her and Hes proteins that are direct targets of the Notch signalling pathway. All members of this family contain a C-terminal WRPW motif. Previous work in this lab demonstrated that Hairy interacts with the Groucho (Gro) corepressor protein via the WRPW motif (Paroush et al., 1994). Subsequently Gro was shown to act as corepressor for other transcriptional regulators including Engrailed and Goosecoid that contain an unrelated motif “FxIxxIL”, known as the eh1 motif (Jimenez et al., 1997, Jimenez et al., 1999). To gain further insight into how the Hairy and related proteins function, we screened for mutations that suppress effects of ectopic Hairy expression in the Drosophila eye. Mutations recovered from this screen include 50 new alleles of gro. Analysis of missense mutations in gro recovered from the screen in combination with structural studies performed by Laura Pickles and Laurence Pearl (Institute of Cancer Research, London), has allowed us to define the molecular basis of how Gro recognises transcription factors containing the WRPW and eh1 peptide motifs in vivo (Jennings et al., 2006).
Binding of the WRPW and eh1 Peptide Motifs to the TLE-WD Domain
|
|
