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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Genetically Modified
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Basic Helix-Loop-Helix Transcription Factors / physiology
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Cells, Cultured
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism
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Drosophila Proteins / physiology*
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Drosophila melanogaster / embryology*
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Drosophila melanogaster / genetics
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Drosophila melanogaster / metabolism
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Embryo, Nonmammalian
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Embryonic Development / genetics*
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Female
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Homeodomain Proteins / genetics
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Homeodomain Proteins / physiology*
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Male
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Protein Binding / physiology
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Repressor Proteins / genetics
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Repressor Proteins / physiology
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Transcription Factors / metabolism
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Ubiquitin-Protein Ligases / genetics
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Ubiquitin-Protein Ligases / physiology*
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Drosophila Proteins
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E(spl)m7-HLH protein, Drosophila
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Hey protein, Drosophila
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Homeodomain Proteins
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Repressor Proteins
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Transcription Factors
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her protein, Drosophila
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Ubiquitin-Protein Ligases
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dgrn protein, Drosophila