title: The Drosophila melanogaster Suppressor of deltex gene, a regulator of the Notch receptor signaling pathway, is an E3 class ubiquitin ligase.
abstract: During development, the Notch receptor regulates many cell fate decisions by a signaling pathway that has been conserved during evolution. One positive regulator of Notch is Deltex, a cytoplasmic, zinc finger domain protein, which binds to the intracellular domain of Notch. Phenotypes resulting from mutations in deltex resemble loss-of-function Notch phenotypes and are suppressed by the mutation Suppressor of deltex [Su(dx)]. Homozygous Su(dx) mutations result in wing-vein phenotypes and interact genetically with Notch pathway genes. We have previously defined Su(dx) genetically as a negative regulator of Notch signaling. Here we present the molecular identification of the Su(dx) gene product. Su(dx) belongs to a family of E3 ubiquitin ligase proteins containing membrane-targeting C2 domains and WW domains that mediate protein-protein interactions through recognition of proline-rich peptide sequences. We have identified a seven-codon deletion in a Su(dx) mutant allele and we show that expression of Su(dx) cDNA rescues Su(dx) mutant phenotypes. Overexpression of Su(dx) also results in ectopic vein differentiation, wing margin loss, and wing growth phenotypes and enhances the phenotypes of loss-of-function mutations in Notch, evidence that supports the conclusion that Su(dx) has a role in the downregulation of Notch signaling.
authors.affiliation: University of Manchester, School of Biological Sciences, Manchester M13 9PT, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Cornell
authors.forename: D A
authors.initials: DA
authors.lastname: Evans
authors.forename: R
authors.initials: R
authors.lastname: Mann
authors.forename: M
authors.initials: M
authors.lastname: Fostier
authors.forename: M
authors.initials: M
authors.lastname: Flasza
authors.forename: M
authors.initials: M
authors.lastname: Monthatong
authors.forename: S
authors.initials: S
authors.lastname: Artavanis-Tsakonas
authors.forename: M
authors.initials: M
authors.lastname: Baron
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000737:chemistry / Q000201:enzymology / Q000235:genetics*; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect / Q000235:genetics*; D016153:Genes, Suppressor / Q000235:genetics; D005816:Genetic Complementation Test; D019476:Insect Proteins / Q000235:genetics; D008025:Ligases / Q000235:genetics*; D008565:Membrane Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D010802:Phylogeny; D011956:Receptors, Cell Surface / Q000502:physiology*; D051880:Receptors, Notch; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014162:Transfection; D044767:Ubiquitin-Protein Ligases; D014921:Wings, Animal / Q000196:embryology / Q000254:growth & development / Q000378:metabolism
chemical_list: C086679:DX protein, Drosophila; D029721:Drosophila Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; C119838:Su(dx) protein, Drosophila; D044767:Ubiquitin-Protein Ligases; D008025:Ligases