Xenopus neuralized is a ubiquitin ligase that interacts with XDelta1 and regulates Notch signaling.
Notch signaling in Drosophila requires a RING finger (RF) protein encoded by neuralized. Here we show that the Xenopus homolog of neuralized (Xneur) is expressed where Notch signaling controls cell fate choices in early embryos. Overexpressing XNeur or putative dominant-negative forms in embryos inhibits Notch signaling. As expected for a RF protein, we show that XNeur fulfills the biochemical requirements of ubiquitin ligases. We also show that wild-type XNeur decreases the cell surface level of the Notch ligand, XDelta1, while putative inhibitory forms of XNeur increase it. Finally, we provide evidence that XNeur acts as a ubiquitin ligase for XDelta1 in vitro. We propose that XNeur plays a conserved role in Notch activation by regulating the cell surface levels of the Delta ligands, perhaps directly, via ubiquitination.
Deblandre
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GA
The Salk Institute for Biological Studies, P.O. Box 85800, La Jolla, CA 92186, USA.
Lai
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Kintner
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D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D008025:Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008845:Microinjections; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017956:Photoreceptor Cells, Invertebrate / Q000502:physiology / Q000648:ultrastructure; D046988:Proteasome Endopeptidase Complex; D011956:Receptors, Cell Surface / Q000378:metabolism; D051880:Receptors, Notch; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D014921:Wings, Animal / Q000033:anatomy & histology; D029867:Xenopus Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000235:genetics / Q000502:physiology*
D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009097:Multienzyme Complexes; C497759:N protein, Drosophila; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D015534:Trans-Activators; D025801:Ubiquitin; D029867:Xenopus Proteins; C064045:delta protein; C443481:NEURL1 protein, Xenopus; D044767:Ubiquitin-Protein Ligases; C071006:neur protein, Drosophila; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D008025:Ligases