title: The Drosophila STUbL protein Degringolade limits HES functions during embryogenesis.
abstract: Degringolade (Dgrn) encodes a Drosophila SUMO-targeted ubiquitin ligase (STUbL) protein similar to that of mammalian RNF4. Dgrn facilitates the ubiquitylation of the HES protein Hairy, which disrupts the repressive activity of Hairy by inhibiting the recruitment of its cofactor Groucho. We show that Hey and all HES family members, except Her, interact with Dgrn and are substrates for its E3 ubiquitin ligase activity. Dgrn displays dynamic subcellular localization, accumulates in the nucleus at times when HES family members are active and limits Hey and HES family activity during sex determination, segmentation and neurogenesis. We show that Dgrn interacts with the Notch signaling pathway by it antagonizing the activity of E(spl)-C proteins. dgrn null mutants are female sterile, producing embryos that arrest development after two or three nuclear divisions. These mutant embryos exhibit fragmented or decondensed nuclei and accumulate higher levels of SUMO-conjugated proteins, suggesting a role for Dgrn in genome stability.
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Barry
authors.forename: Mona
authors.initials: M
authors.lastname: Abed
authors.forename: Dorit
authors.initials: D
authors.lastname: Kenyagin
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Werwie
authors.forename: Olga
authors.initials: O
authors.lastname: Boico
authors.forename: Amir
authors.initials: A
authors.lastname: Orian
authors.forename: Susan M
authors.initials: SM
authors.lastname: Parkhurst
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D008297:Male; D011485:Protein Binding / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; C121960:E(spl)m7-HLH protein, Drosophila; C120390:Hey protein, Drosophila; C507971:her protein, Drosophila; C558536:dgrn protein, Drosophila