Monoubiquitination and endocytosis direct γ-secretase cleavage of activated Notch receptor
العنوان: | Monoubiquitination and endocytosis direct γ-secretase cleavage of activated Notch receptor |
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المؤلفون: | Christel Brou, Frédérique Logeat, Annie Olry, Odile LeBail, Emmanuelle Six, Neetu Gupta-Rossi, Patricia Chastagner, Alain Israël |
المساهمون: | Biologie Moléculaire de l'Expression Génique, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS) |
المصدر: | The Journal of Cell Biology Journal of Cell Biology Journal of Cell Biology, 2004, 166 (1), pp.73-83. ⟨10.1083/jcb.200310098⟩ Journal of Cell Biology, Rockefeller University Press, 2004, 166 (1), pp.73-83. ⟨10.1083/jcb.200310098⟩ |
بيانات النشر: | The Rockefeller University Press, 2004. |
سنة النشر: | 2004 |
مصطلحات موضوعية: | MESH: Signal Transduction, Time Factors, MESH: Sequence Homology, Amino Acid, MESH: Microscopy, Fluorescence, MESH: Amino Acid Sequence, Ligands, MESH: Protein Structure, Tertiary, 0302 clinical medicine, Ubiquitin, MESH: Ligands, Monoubiquitination, MESH: Microscopy, Confocal, MESH: Precipitin Tests, Aspartic Acid Endopeptidases, MESH: Animals, MESH: Endopeptidases, Research Articles, Notch, presenilins, endocytosis, ubiquitin, γ-secretase, 0303 health sciences, Microscopy, Confocal, biology, MESH: Immunoblotting, Receptors, Notch, MESH: Presenilin-1, Endocytosis, Cell biology, Ectodomain, MESH: Endocytosis, MESH: Membrane Proteins, MESH: Aspartic Acid Endopeptidases, Signal transduction, Protein Binding, Signal Transduction, MESH: Ubiquitin, Immunoblotting, Molecular Sequence Data, Notch signaling pathway, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Transfection, Presenilin, Article, Cell Line, 03 medical and health sciences, Endopeptidases, Presenilin-1, MESH: Protein Binding, Animals, Humans, MESH: Lysine, Amino Acid Sequence, 030304 developmental biology, MESH: Molecular Sequence Data, MESH: Humans, Sequence Homology, Amino Acid, MESH: Transfection, Lysine, MESH: Time Factors, Membrane Proteins, Cell Biology, Precipitin Tests, MESH: Cell Line, Protein Structure, Tertiary, MESH: Hela Cells, MESH: Amyloid Precursor Protein Secretases, Microscopy, Fluorescence, biology.protein, Amyloid Precursor Protein Secretases, MESH: Receptors, Notch, Amyloid precursor protein secretase, 030217 neurology & neurosurgery, HeLa Cells |
الوصف: | International audience; Activation of mammalian Notch receptor by its ligands induces TNFalpha-converting enzyme-dependent ectodomain shedding, followed by intramembrane proteolysis due to presenilin (PS)-dependent gamma-secretase activity. Here, we demonstrate that a new modification, a monoubiquitination, as well as clathrin-dependent endocytosis, is required for gamma-secretase processing of a constitutively active Notch derivative, DeltaE, which mimics the TNFalpha-converting enzyme-processing product. PS interacts with this modified form of DeltaE, DeltaEu. We identified the lysine residue targeted by the monoubiquitination event and confirmed its importance for activation of Notch receptor by its ligand, Delta-like 1. We propose a new model where monoubiquitination and endocytosis of Notch are a prerequisite for its PS-dependent cleavage, and discuss its relevance for other gamma-secretase substrates. |
اللغة: | English |
تدمد: | 1540-8140 0021-9525 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::42bd1832d1eb8b770afd4f43d16a800dTest http://europepmc.org/articles/PMC2172142Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....42bd1832d1eb8b770afd4f43d16a800d |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15408140 00219525 |
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