High impact information on gro

• EGFR signaling attenuates Groucho-dependent repression to antagonize Notch transcriptional output [1].
• Groucho-mediated transcriptional repression establishes progenitor cell pattern and neuronal fate in the ventral neural tube [2].
• We find that the groucho (gro) protein binds specifically to hairy and also to hairy-related bHLH proteins encoded by deadpan and the Enhancer of split complex [3].
• Notch and the m9/10 gene (groucho) of the Enhancer of split (E(spI)) complex are members of the "Notch group" of genes, which is required for a variety of cell fate choices in Drosophila [4].
• Drosophila Tcf and Groucho interact to repress Wingless signalling activity [5].

Biological context of gro

• Reduction of gro or dCtBP function enhances H mutant phenotypes and suppresses N phenotypes in the adult mechanosensory bristle [6].
• Enhancer of split [E(spl)(D)] is a gro-independent, hypermorphic mutation in Drosophila [7].
• We show that torso signalling permits terminal gap gene expression by antagonising Gro-mediated repression [8].
• Here, we identify several missense mutations in Drosophila Gro, which demonstrate peptide binding to the central pore of the WD (WD40) beta propeller domain in vitro and in vivo [9].
• We find that the conserved C-terminal EYA domain negatively regulates EYA transactivation potential, and that GROUCHO-SINE OCULIS (SO) interactions provide another mechanism for negative regulation of EYA-SO target genes [10].

Anatomical context of gro

• Two members of the mammalian Groucho family were expressed in trophoblasts; TLE3 was expressed broadly in the giant cell, spongiotrophoblast, and labyrinthine regions, whereas TLE2 was limited to giant cells and focal regions of the spongiotrophoblast [11].
• We demonstrate that this domain (GscR) mediates efficient repression in Drosophila blastoderm embryos and that repression by GscR requires Gro function [12].
• Previous studies indicated that a conserved domain in Gro, termed the Q domain, was required for repression in cultured cells and mediated homotetramerization [13].
• Using expression of activator and repressor constructs of six1 or co-expression of wild-type six1 with activating or repressing co-factors (eya1 and groucho, respectively), we demonstrate that Six1 inhibits neural crest and epidermal genes via transcriptional repression and enhances PPE genes via transcriptional activation [14].
• R-esp1, a rat homologue of drosophila groucho, is differentially expressed after optic nerve crush and mediates NGF-induced survival of PC12 cells [15].

Associations of gro with chemical compounds

• Comparison between diverse eh1 motifs reveals a bias for the phosphoacceptor amino acids serine and threonine at a fixed position, and a mutational analysis of Odd-skipped indicates that these residues are critical for efficient interactions with Groucho and for repression in vivo [16].
• We determined, via a variety of hydrodynamic measurements as well as protein cross-linking, that native Gro is a tetramer in solution and that tetramerization is mediated by two putative amphipathic alpha-helices (termed leucine zipper-like motifs) found in the N-terminal region [17].

Physical interactions of gro

• The Groucho protein interacts with Hairy-related transcription factors to regulate segmentation, neurogenesis and sex determination [18].
• The Slp1 protein contains a protein motif (EH1) which mediates binding to the transcriptional corepressor Groucho (Gro) [19].
• The latter result correlates with an ability of this En domain to bind to Gro in vitro [20].

Regulatory relationships of gro

• Torso signalling regulates terminal patterning in Drosophila by antagonising Groucho-mediated repression [8].
• Finally, mutations in the Drosophila groucho gene also suppress wingless and armadillo mutant phenotypes as Groucho physically interacts with dTcf and is required for its full repressor activity [5].
• Receptor tyrosine kinase signaling regulates different modes of Groucho-dependent control of Dorsal [21].
• groucho and hedgehog regulate engrailed expression in the anterior compartment of the Drosophila wing [22].

Other interactions of gro

• Hairless-mediated repression of notch target genes requires the combined activity of Groucho and CtBP corepressors [23].
• Here we have investigated the requirement for Gro and CtBP in Hairless-mediated repression [23].
• Huckebein repressor activity in Drosophila terminal patterning is mediated by Groucho [24].
• We have previously implicated Groucho in Drosophila embryonic terminal patterning, showing that it is required to confine tailless and huckebein terminal gap gene expression to the pole regions of the embryo [24].
• While both dCtBP and Groucho are required for proper Hairy function, their properties are very different [25].

Analytical, diagnostic and therapeutic context of gro

• We examined the interplay between DI, Gro and Dri on the hkb enhancer and show that when acting over a distance, Gro abolishes rather than converts DI activator function [21].
• Using immunoprecipitation and in vitro pull-down assays, we show that NK-4 directly interacts with the Groucho corepressor, for which the homeodomain is required [26].
• Immunocytochemistry has been used to investigate whether the co-repressor Groucho (Gro; vertebrate homolog: TLE) and the co-factor Extradenticle (Exd; vertebrate homolog: Pbx) are expressed in the cercal system [27].

References