The Drosophila Groucho (Gro) protein was the founding member of the family of 
transcriptional co-repressor proteins that now includes the transducin-like 
enhancer of split (TLE) and Grorelated gene (Grg) proteins in vertebrates. Gro 
family proteins do not bind DNA directly, but are recruited by a diverse profile 
of transcription factors, including members of the Hes, Runx, Nkx, LEF1/Tcf, 
Pax, Six and c-Myc families. The primary structure of Gro proteins includes five 
identifiable regions, of which the most highly conserved are the amino-terminal 
glutamine-rich Q domain and the carboxy-terminal WD-repeat domain. The Q domain 
contains two coiled-coil motifs that facilitate oligomerization into tetramers 
and binding to some transcription factors. The WD domain folds to form a 
beta-propeller, which mediates protein-protein interactions. Many transcription 
factors interact with the WD domain via a short peptide motif that falls into 
either of two classes: WRPW and related tetrapeptides; and the 'eh1' motif 
(FxIxxIL). Gro family proteins are broadly expressed during development and in 
the adult. They have essential functions in many developmental pathways 
(including Notch and Wnt signaling) and are implicated in the pathogenesis of 
some cancers. The molecular mechanisms through which Gro proteins act to repress 
transcription are not yet well understood. It is becoming clear that Gro 
proteins have different modes of action in vivo dependent on biological context 
and these include direct and indirect modification of chromatin structure at 
target genes.