The Notch receptor, which is involved in numerous cell fate decisions invertebrates and vertebrates, synthesized as a 300-kDa precursor molecule (p300). We show here that proteolytic processing of p300 an essential step the formation biologically active receptor because only cleaved fragments are present at surface. Our results confirm extend recent reports indicating exists plasma membrane heterodimeric molecule, but disagree to nature protease responsible for cleavage takes place...

The Notch signaling pathway is essential in many cell fate decisions invertebrates as well vertebrates. After ligand binding, a two-step proteolytic cleavage releases the intracellular part of receptor which translocates to nucleus and acts transcriptional activator. Although Notch-induced transcription genes has been reported extensively, its endogenous nuclear form seldom visualized. We report that domain Notch1 stabilized by proteasome inhibitors substrate for polyubiquitination vitro....

The Notch receptor is involved in many cell fate determination events vertebrates and invertebrates. It has been shown Drosophila melanogaster that Delta-dependent signaling activates the transcription factor Suppressor of Hairless, leading to an increased expression Enhancer Split genes. Genetic evidence also implicated kuzbanian gene, which encodes a disintegrin metalloprotease, pathway. By using two-cell coculture assay, we show here vertebrate Dl-1 Notch-1 cascade. Consistent with...

Notch signaling is involved in numerous cell fate decisions invertebrates and vertebrates. The receptor a type I transmembrane (TM) protein that undergoes two proteolytic steps after ligand binding, first by an ADAM (a distintegrin metalloprotease) the extracellular region, followed γ-secretase-mediated cleavage inside TM domain. We demonstrate here murine Delta1 (Dll1) same sequence of cleavages, apparently signal-independent manner. Identification ADAM-mediated shedding site localized 10...

Activation of mammalian Notch receptor by its ligands induces TNFα-converting enzyme–dependent ectodomain shedding, followed intramembrane proteolysis due to presenilin (PS)-dependent γ-secretase activity. Here, we demonstrate that a new modification, monoubiquitination, as well clathrin-dependent endocytosis, is required for processing constitutively active derivative, ΔE, which mimics the enzyme–processing product. PS interacts with this modified form ΔEu. We identified lysine residue...

The metalloprotease ADAM10 mediates the shedding of ectodomain various cell membrane proteins, including APP, precursor amyloid peptide Aβ, and Notch receptors following ligand binding. associates with members an evolutionary conserved subgroup tetraspanins, referred to as TspanC8, which regulate its exit from endoplasmic reticulum. Here we show that 4 these TspanC8 (Tspan5, Tspan14, Tspan15 Tspan33) positively surface expression levels differentially impact ADAM10-dependent activation...

Glioblastoma (GBM) is the most aggressive brain cancer and its relapse after surgery, chemo radiotherapy appears to be led by GBM stem cells (GSCs). Also, tumor networking intercellular communication play a major role in driving therapy-resistance. Tunneling Nanotubes (TNTs), thin membranous open-ended channels connecting distant cells, have been observed several types of cancer, where they emerge drive more malignant phenotype. Here, we investigated whether are capable intercommunicate...

We have purified the sequence-specific DNA-binding protein KBF2 and cloned corresponding cDNA, which is derived from previously described RBP-J kappa gene, human homolog of Drosophila Suppressor Hairless [Su(H)] gene. Deletion studies Su(H) proteins allowed us to define a domain conserved during evolution. Because mutant alleles exhibit dose-sensitive interactions with (H) loss-of-function mutations, we investigated whether or directly interact H in vitro. show here that can inhibit DNA...

The regulation of Notch signaling heavily relies on ubiquitination events. Drosophila Su(dx), a member the HECT family ubiquitin-ligases, has been described as negative regulator signaling, acting post-endocytic sorting Notch. mammalian ortholog Itch/AIP4, shown to have multiple substrates, including Notch, but precise events regulated by Itch/AIP4 in pathway not identified yet.Using Itch-/- fibroblasts expressing Notch1 receptor, we show that Itch is necessary for activation, rather...

Article12 November 2020Open Access Transparent process Fate and propagation of endogenously formed Tau aggregates in neuronal cells Patricia Chastagner Unité de Trafic Membranaire et Pathogenèse, Institut Pasteur, Paris, FranceThese authors contributed equally to this work Search for more papers by author Frida Loria Jessica Y Vargas France Josh Tois Marc I Diamond Center Alzheimer's Neurodegenerative Diseases, Peter O'Donnell Jr. Brain Institute, University Texas Southwestern Medical...

Activation of the mammalian Notch receptor after ligand binding relies on a succession events including metalloprotease-cleavage, endocytosis, monoubiquitination, and eventually processing by gamma-secretase, giving rise to soluble, transcriptionally active molecule. The Notch1 was proposed be monoubiquitinated before its gamma-secretase cleavage; targeted lysine has been localized submembrane domain. Investigating how this step might regulated deubiquitinase (DUB) activity will provide new...

The very conserved Notch pathway is used iteratively during development and adulthood to regulate cell fates. activation relies on interactions between neighboring cells, through the binding of receptors their ligands, both transmembrane molecules. This inter-cellular contact initiates a cascade events eventually transforming surface receptor into nuclear factor acting transcription specific target genes. review highlights how various processes undergone by ligands that are linked...

ABSTRACT For many years, β-arrestins have been known to be involved in G-protein-coupled receptor (GPCR) desensitization. However, belong a family of proteins that act as multifunctional scaffolding proteins, particular during trafficking transmembrane receptors. The arrestin comprises visual arrestins, and α-arrestins. In mammals, the functions α-arrestins are beginning elucidated, they described versatile adaptors link GPCRs or Notch E3 ubiquitin ligases endocytic factors. These can...

Notch signaling is critical for development and adult tissue physiology, controlling cell fate in a context-dependent manner. Upon ligand binding, the transmembrane receptor undergoes two ordered proteolytic cleavages releasing intracellular domain, which regulates transcription of target genes. The strength crucial importance depends notably on quantity at surface. Using an shRNA library screen monitoring trafficking degradation absence ligand, we identified mammalian USP12 its Drosophila...

Summary Notch signaling is a conserved pathway implicated in embryogenesis and adult tissue maintenance. strength strictly regulated, notably by maintaining controlled pool of functional receptor at the cell surface. Mammalian non-activated internalized, ubiquitylated Itch E3 ubiquitin ligase degraded lysosomes. Here, we show that β-arrestins are necessary for Itch–Notch interaction Itch-driven ubiquitylation degradation Notch. Interestingly, do not directly bind but heterodimerize with...

Journal Article Different TBP-associated factors are required for mediating the stimulation of transcription in vitro by acidic transactivator GAL-VP16 and two nonacidic activation functions estrogen receptor Get access Christel Brou, Brou Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Unité 184 Biologie et Genie I'INSERM, Institut Chimie Biologique, Faculté Médecine11 rue Humann, 67085 Strasbourg Cedex, France Search other works this author on: Oxford Academic PubMed Google...