title: Nipped-A, the Tra1/TRRAP subunit of the Drosophila SAGA and Tip60 complexes, has multiple roles in Notch signaling during wing development.
abstract: The Notch receptor controls development by activating transcription of specific target genes in response to extracellular signals. The factors that control assembly of the Notch activator complex on target genes and its ability to activate transcription are not fully known. Here we show, through genetic and molecular analysis, that the Drosophila Nipped-A protein is required for activity of Notch and its coactivator protein, mastermind, during wing development. Nipped-A and mastermind also colocalize extensively on salivary gland polytene chromosomes, and reducing Nipped-A activity decreases mastermind binding. Nipped-A is the fly homologue of the yeast Tra1 and human TRRAP proteins and is a key component of both the SAGA and Tip60 (NuA4) chromatin-modifying complexes. We find that, like Nipped-A, the Ada2b component of SAGA and the domino subunit of Tip60 are also required for mastermind function during wing development. Based on these results, we propose that Nipped-A, through the action of the SAGA and Tip60 complexes, facilitates assembly of the Notch activator complex and target gene transcription.
authors.affiliation: Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, 1402 South Grand Boulevard, Saint Louis, MO 63104, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Gause
authors.forename: Joel C
authors.initials: JC
authors.lastname: Eissenberg
authors.forename: Amy F
authors.initials: AF
authors.lastname: Macrae
authors.forename: Maia
authors.initials: M
authors.lastname: Dorsett
authors.forename: Ziva
authors.initials: Z
authors.lastname: Misulovin
authors.forename: Dale
authors.initials: D
authors.lastname: Dorsett
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000254:growth & development*; D004625:Embryo, Nonmammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014680:Veins / Q000254:growth & development; D014921:Wings, Animal / Q000254:growth & development*
chemical_list: C470558:Ada2a protein, Drosophila; D048868:Adaptor Proteins, Signal Transducing; D029721:Drosophila Proteins; D046912:Multiprotein Complexes; C497759:N protein, Drosophila; C511055:NIPPED-A protein, Drosophila; D009687:Nuclear Proteins; D021122:Protein Subunits; D051880:Receptors, Notch; D014157:Transcription Factors; C085316:mam protein, Drosophila; C113829:transformation-transcription domain-associated protein; D051548:Histone Acetyltransferases; C511056:Tip60 protein, Drosophila