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The Drosophila STUbL protein Degringolade limits HES functions during embryogenesis.

TitleThe Drosophila STUbL protein Degringolade limits HES functions during embryogenesis.
Publication TypeJournal Article
Year of Publication2011
AuthorsBarry KC, Abed M, Kenyagin D, Werwie TR, Boico O, Orian A, Parkhurst SM
JournalDevelopment (Cambridge, England)
Date Published2011 May
KeywordsAnimals, Animals, Genetically Modified, Basic Helix-Loop-Helix Transcription Factors, Protein Binding, Cells, Cultured, Drosophila melanogaster, Drosophila Proteins, Embryo, Nonmammalian, Neurons, Male, Female, Homeodomain Proteins, Transcription Factors, Repressor Proteins, Ubiquitin-Protein Ligases

<p>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.</p>

Alternate JournalDevelopment