Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1998-05

AUTHORS

Eric H. Schroeter, Jeffrey A. Kisslinger, Raphael Kopan

ABSTRACT

Notch proteins are ligand-activated transmembrane receptors involved in cell-fate selection throughout development1,2,3. No known enzymatic activity is contained within Notch and the molecular mechanism by which it transduces signals across the cell membrane is poorly understood. In many instances, Notch activation results in transcriptional changes in the nucleus through an association with members of the CSL family of DNA-binding proteins (where CSL stands for CBF1, Su(H), Lag-1)1,2,3,4. As Notch is located in the plasma membrane and CSL is a nuclear protein, two models have been proposed to explain how they interact (Fig. 1) . The first suggests that the two interact transiently at the membrane1,5,6,7. The second postulates that Notch is cleaved by a protease, enabling the cleaved fragment to enter the nucleus6,8,9,10,11,12,13,14. Here we show that signalling by a constitutively active membrane-bound Notch-1 protein requires the proteolytic release of the Notch intracellular domain (NICD), which interacts preferentially with CSL. Very small amounts of NICD are active, explaining why it is hard to detect in the nucleus in vivo. We also show that it is ligand binding that induces release of NICD.Figure 1Different predictions are made by two models of Notch signalling.a, Models not invoking processing propose that interactions between Notch and CSL at the membrane may be sufficient to transduce a signal. Thus, ligand-regulated NICD release is not expected to be necessary for signalling. b, The processing model suggests that Notch signalling requires the release of NICD, which is capable of direct interaction with CSL in the nucleus, to turn on transcription of target genes. This model predicts that NICD release is regulated by ligand binding and that blocking proteolysis interferes with signalling. Notch-1 domain symbols as in Fig. 2. More... »

PAGES

382-386

References to SciGraph publications

Journal

TITLE

Nature

ISSUE

6683

VOLUME

393

Related Patents

  • Method For Identifying Modulators Of Notch Signaling
  • Gamma Secretase Notch Biomarkers
  • Notch1 Receptor Binding Agents And Methods Of Use Thereof
  • Notch1 Binding Agents And Methods Of Use Thereof
  • Method For Identifying Modulators Of Notch Signaling
  • Extracellular Markers Whereby Notch Signal Transduction Can Be Detected; These Peptides (N Beta ) Are Released From Cells In Proportion To Notch Signal Depending On Presenilin; By Detecting These Peptides, Notch Signal Transduction, Cell Differentiation, Apoptosis, Alzheimer's Disease Can Be Detected
  • Methods And Compositions For Stimulation Of Cell Proliferation And Provision Of Biologically Active Mixtures Of Fgf2 Isoforms
  • Gamma Secretase Notch Biomarkers
  • Chimeric Sensor Protein And Methods Of Use Thereof
  • Cancer Markers
  • Activated Forms Of Notch And Methods Based Thereon
  • Identifying And Isolating A Precursor Cell; Of Increasing Insulin Synthesis From A Pancreatic B-Cell; Contacting A Pancreatic Cell Sample With A Marker That Selectively Binds A Notch Receptor And Detecting The Bound Marker, The Cell That Binds The Marker Being A Pancreatic Precursor Cell
  • Inhibitors Of The Notch Signalling Pathway And Secretion For Use In Medicine
  • Methods And Compositions For Treatment Of Retinal Degeneration
  • Anti-Notch Nrr Antibodies And Methods Using Same
  • Compositions And Methods For Diagnosing And Treating Cancer
  • Inhibitors Of Notch Signaling Pathway And Use Thereof In Treatment Of Cancers
  • Anti-Notch3 Antibodies And Antibody-Drug Conjugates
  • Detecting Notch Signal Transduction By Measurement Of Gene Expression; Screening For Cancer And Cell Proliferation
  • Antibodies To A Non-Ligand Binding Region Of At Least Two Notch Receptors
  • Activated Forms Of Notch And Methods Based Thereon
  • Coumarin-Based Compounds
  • Anti-Notch1 Antibodies
  • Chimeric Sensor Protein And Methods Of Use Thereof
  • Polynucleotides Encoding Anti-Notch1 Nrr Antibody Polypeptides
  • Anti Notch-1 Antibodies
  • Helical Peptidomimetics With Enhanced Activity
  • Activated Amino- And Carboxy-Terminal Forms Of Notch
  • Identifying Gamma -Secretase Inhibitors That Exhibit Reduced Induction Of Goblet Cell Metaplasia; Detecting Mucin-2 Induction Or Mucin-5ac Induction In Notch Expressing Ht29 Cells Contacted With A Compound That Inhibits Gamma -Secretase
  • Fused, Tricyclic Sulfonamide Inhibitors Of Gamma Secretase
  • Cancer Markers
  • Methods For Identifying Modulators Of Notch Activation
  • Manipulation Of Non-Terminally Differentiated Cells Using The Notch Pathway
  • Gamma-Secretase Modulatory Compounds, Methods For Identifying Same, And Uses Therefor
  • N-Substituted Benzene Sulfonamides
  • N-Substituted Benzene Sulfonamides
  • Method Of Generating A Dosing Schedule Using Gamma Secretase Notch Biomarkers
  • Method Of Treating Cancer By Administering A Monoclonal Antibody That Binds Human Notch2 And Notch3
  • Regulation Of Gsk-3Α Activity For The Treatment Or Prevention Of Alzheimer's Disease
  • Methods And Compositions For Stimulation Of Cell Proliferation And Provision Of Biologically Active Mixtures Of Fgf2 Isoforms
  • Anti-Notch1 Nrr Antibodies
  • Inhibitors Of Notch Signalling Pathway And Use Thereof In Treatment Of Cancers
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/30756

    DOI

    http://dx.doi.org/10.1038/30756

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1041325757

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/9620803


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biological Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biochemistry and Cell Biology", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "3T3 Cells", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Amino Acid Sequence", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Animals", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Basic Helix-Loop-Helix Transcription Factors", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Brefeldin A", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Line", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Nucleus", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cyclopentanes", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "DNA-Binding Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Gene Expression Regulation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Genes, Reporter", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Golgi Apparatus", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Homeodomain Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Ligands", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Membrane Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mice", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Molecular Sequence Data", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Monensin", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mutagenesis", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Peptide Fragments", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Promoter Regions, Genetic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Protein Processing, Post-Translational", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Receptor, Notch1", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Receptors, Cell Surface", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Signal Transduction", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Transcription Factor HES-1", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Transcription Factors", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Transfection", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Division of Dermatology and the Department of Molecular Biology and Pharmacology, Washington University, Box 8123, 4940 Parkview Place, 63110, St Louis, Missouri, USA", 
              "id": "http://www.grid.ac/institutes/grid.4367.6", 
              "name": [
                "Division of Dermatology and the Department of Molecular Biology and Pharmacology, Washington University, Box 8123, 4940 Parkview Place, 63110, St Louis, Missouri, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Schroeter", 
            "givenName": "Eric H.", 
            "id": "sg:person.0742772124.34", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0742772124.34"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Division of Dermatology and the Department of Molecular Biology and Pharmacology, Washington University, Box 8123, 4940 Parkview Place, 63110, St Louis, Missouri, USA", 
              "id": "http://www.grid.ac/institutes/grid.4367.6", 
              "name": [
                "Division of Dermatology and the Department of Molecular Biology and Pharmacology, Washington University, Box 8123, 4940 Parkview Place, 63110, St Louis, Missouri, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kisslinger", 
            "givenName": "Jeffrey A.", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Division of Dermatology and the Department of Molecular Biology and Pharmacology, Washington University, Box 8123, 4940 Parkview Place, 63110, St Louis, Missouri, USA", 
              "id": "http://www.grid.ac/institutes/grid.4367.6", 
              "name": [
                "Division of Dermatology and the Department of Molecular Biology and Pharmacology, Washington University, Box 8123, 4940 Parkview Place, 63110, St Louis, Missouri, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kopan", 
            "givenName": "Raphael", 
            "id": "sg:person.0660157721.51", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0660157721.51"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/ng0797-212", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044650583", 
              "https://doi.org/10.1038/ng0797-212"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/377355a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1019765251", 
              "https://doi.org/10.1038/377355a0"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "1998-05", 
        "datePublishedReg": "1998-05-01", 
        "description": "Notch proteins are ligand-activated transmembrane receptors involved in cell-fate selection throughout development1,2,3. No known enzymatic activity is contained within Notch and the molecular mechanism by which it transduces signals across the cell membrane is poorly understood. In many instances, Notch activation results in transcriptional changes in the nucleus through an association with members of the CSL family of DNA-binding proteins (where CSL stands for CBF1, Su(H), Lag-1)1,2,3,4. As Notch is located in the plasma membrane and CSL is a nuclear protein, two models have been proposed to explain how they interact (Fig. 1) . The first suggests that the two interact transiently at the membrane1,5,6,7. The second postulates that Notch is cleaved by a protease, enabling the cleaved fragment to enter the nucleus6,8,9,10,11,12,13,14. Here we show that signalling by a constitutively active membrane-bound Notch-1 protein requires the proteolytic release of the Notch intracellular domain (NICD), which interacts preferentially with CSL. Very small amounts of NICD are active, explaining why it is hard to detect in the nucleus in vivo. We also show that it is ligand binding that induces release of NICD.Figure 1Different predictions are made by two models of Notch signalling.a, Models not invoking processing propose that interactions between Notch and CSL at the membrane may be sufficient to transduce a signal. Thus, ligand-regulated NICD release is not expected to be necessary for signalling. b, The processing model suggests that Notch signalling requires the release of NICD, which is capable of direct interaction with CSL in the nucleus, to turn on transcription of target genes. This model predicts that NICD release is regulated by ligand binding and that blocking proteolysis interferes with signalling. Notch-1 domain symbols as in Fig. 2.", 
        "genre": "article", 
        "id": "sg:pub.10.1038/30756", 
        "isAccessibleForFree": false, 
        "isPartOf": [
          {
            "id": "sg:journal.1018957", 
            "issn": [
              "0028-0836", 
              "1476-4687"
            ], 
            "name": "Nature", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "6683", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "393"
          }
        ], 
        "keywords": [
          "Notch intracellular domain", 
          "intracellular domain", 
          "proteolytic release", 
          "known enzymatic activity", 
          "DNA-binding proteins", 
          "cell fate selection", 
          "CSL family", 
          "Notch proteins", 
          "transcriptional changes", 
          "nuclear proteins", 
          "transmembrane receptors", 
          "target genes", 
          "plasma membrane", 
          "Notch activation", 
          "Notch signaling", 
          "Notch-1 protein", 
          "molecular mechanisms", 
          "ligand binding", 
          "cell membrane", 
          "direct interaction", 
          "enzymatic activity", 
          "protein", 
          "Notch-1", 
          "membrane", 
          "Notch", 
          "CBF1", 
          "induces release", 
          "nucleus", 
          "transcription", 
          "CSL", 
          "genes", 
          "signaling", 
          "domain", 
          "protease", 
          "interacts", 
          "binding", 
          "release", 
          "interaction", 
          "fragments", 
          "activation", 
          "vivo", 
          "family", 
          "receptors", 
          "interferes", 
          "members", 
          "signals", 
          "mechanism", 
          "selection", 
          "ligands", 
          "activity", 
          "small amount", 
          "changes", 
          "association", 
          "amount", 
          "model", 
          "prediction", 
          "propose", 
          "lag", 
          "instances", 
          "Fig. 2", 
          "symbols", 
          "processing model"
        ], 
        "name": "Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain", 
        "pagination": "382-386", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1041325757"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/30756"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "9620803"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/30756", 
          "https://app.dimensions.ai/details/publication/pub.1041325757"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-11-24T20:48", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20221124/entities/gbq_results/article/article_293.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1038/30756"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/30756'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/30756'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/30756'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/30756'


     

    This table displays all metadata directly associated to this object as RDF triples.

    256 TRIPLES      21 PREDICATES      118 URIs      108 LITERALS      35 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/30756 schema:about N00cb800a818d442383137c53a6682d49
    2 N1a79be1f0d2543afb7799cb1e653692a
    3 N2444e90e0703443c820bedd29332c078
    4 N32781423ec4849638a9e7b124b473bed
    5 N38b4fd98458643cd9edb891caf0b48c2
    6 N3bbc9985c06b4aceb1333e815dc2f48e
    7 N42eb83074a1b43b19994276499fdb92f
    8 N500e5715526e4522b27f87ba3d12481f
    9 N545a143519414cc5bf750021533a782f
    10 N5c5bafd80b39423da333296b57241dcb
    11 N5f5583a6b4da4865acfa21d6e06bb576
    12 N740ce2082a864331a2bc3d173b92aa24
    13 N745a55cc90094800a9c322287d4064af
    14 N76657cf488594473b4d793a496d6344b
    15 N7697ab7190844af2a62369dda4e39af0
    16 N85e8a9ece7d94f2797a7b175283bec84
    17 N95221ca66ff145e2b4eb2cbec16232c3
    18 N96ec738c1bca4b1b9db3c15d58422d14
    19 N9b52ed9365324c43a132f2e971a1517e
    20 Naa06a90b318e4e15b94757fb5c4541b1
    21 Naa8f905c08d9439c916f6af8b9923315
    22 Nac33910c96ce482db48ad0753ee77e29
    23 Naf9ec3ee13d949d3a6f25efbec0a34c2
    24 Nc8b36465c98b4681977233bc49e914e2
    25 Nd25b88ead06f4066ba3a9c33ed235628
    26 Ne0218dd1df834365be901ae1e8427f78
    27 Ne0e919b34ef645d49b8ec2e9e6cc67a8
    28 Nf42a56d19ccf4c2ca7704485b8e66d7d
    29 anzsrc-for:06
    30 anzsrc-for:0601
    31 schema:author N9bc130cad9784d6dae8b4470d80c64e2
    32 schema:citation sg:pub.10.1038/377355a0
    33 sg:pub.10.1038/ng0797-212
    34 schema:datePublished 1998-05
    35 schema:datePublishedReg 1998-05-01
    36 schema:description Notch proteins are ligand-activated transmembrane receptors involved in cell-fate selection throughout development1,2,3. No known enzymatic activity is contained within Notch and the molecular mechanism by which it transduces signals across the cell membrane is poorly understood. In many instances, Notch activation results in transcriptional changes in the nucleus through an association with members of the CSL family of DNA-binding proteins (where CSL stands for CBF1, Su(H), Lag-1)1,2,3,4. As Notch is located in the plasma membrane and CSL is a nuclear protein, two models have been proposed to explain how they interact (Fig. 1) . The first suggests that the two interact transiently at the membrane1,5,6,7. The second postulates that Notch is cleaved by a protease, enabling the cleaved fragment to enter the nucleus6,8,9,10,11,12,13,14. Here we show that signalling by a constitutively active membrane-bound Notch-1 protein requires the proteolytic release of the Notch intracellular domain (NICD), which interacts preferentially with CSL. Very small amounts of NICD are active, explaining why it is hard to detect in the nucleus in vivo. We also show that it is ligand binding that induces release of NICD.Figure 1Different predictions are made by two models of Notch signalling.a, Models not invoking processing propose that interactions between Notch and CSL at the membrane may be sufficient to transduce a signal. Thus, ligand-regulated NICD release is not expected to be necessary for signalling. b, The processing model suggests that Notch signalling requires the release of NICD, which is capable of direct interaction with CSL in the nucleus, to turn on transcription of target genes. This model predicts that NICD release is regulated by ligand binding and that blocking proteolysis interferes with signalling. Notch-1 domain symbols as in Fig. 2.
    37 schema:genre article
    38 schema:isAccessibleForFree false
    39 schema:isPartOf N16bba9dd394a4b38813ec90a90ad7d63
    40 N4023dc2669d84c4cbb51611a73f743cb
    41 sg:journal.1018957
    42 schema:keywords CBF1
    43 CSL
    44 CSL family
    45 DNA-binding proteins
    46 Fig. 2
    47 Notch
    48 Notch activation
    49 Notch intracellular domain
    50 Notch proteins
    51 Notch signaling
    52 Notch-1
    53 Notch-1 protein
    54 activation
    55 activity
    56 amount
    57 association
    58 binding
    59 cell fate selection
    60 cell membrane
    61 changes
    62 direct interaction
    63 domain
    64 enzymatic activity
    65 family
    66 fragments
    67 genes
    68 induces release
    69 instances
    70 interaction
    71 interacts
    72 interferes
    73 intracellular domain
    74 known enzymatic activity
    75 lag
    76 ligand binding
    77 ligands
    78 mechanism
    79 members
    80 membrane
    81 model
    82 molecular mechanisms
    83 nuclear proteins
    84 nucleus
    85 plasma membrane
    86 prediction
    87 processing model
    88 propose
    89 protease
    90 protein
    91 proteolytic release
    92 receptors
    93 release
    94 selection
    95 signaling
    96 signals
    97 small amount
    98 symbols
    99 target genes
    100 transcription
    101 transcriptional changes
    102 transmembrane receptors
    103 vivo
    104 schema:name Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain
    105 schema:pagination 382-386
    106 schema:productId N60f4aa401cf748b6a77a3ca940a16ebc
    107 N7c42919fe22b4399926d3cd85de4ac67
    108 N83f5e5f238da48d8ab5b15d843d5fd7a
    109 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041325757
    110 https://doi.org/10.1038/30756
    111 schema:sdDatePublished 2022-11-24T20:48
    112 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    113 schema:sdPublisher N3ee21b5db796442a8487119ed38c0908
    114 schema:url https://doi.org/10.1038/30756
    115 sgo:license sg:explorer/license/
    116 sgo:sdDataset articles
    117 rdf:type schema:ScholarlyArticle
    118 N00cb800a818d442383137c53a6682d49 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    119 schema:name Transcription Factor HES-1
    120 rdf:type schema:DefinedTerm
    121 N157721ce68774108a6c62581177eda6f rdf:first N8d3cc4e918ae4961b473d3ef6b35067a
    122 rdf:rest N6a4b0b1a3fc64991b81448ebc18695ec
    123 N16bba9dd394a4b38813ec90a90ad7d63 schema:volumeNumber 393
    124 rdf:type schema:PublicationVolume
    125 N1a79be1f0d2543afb7799cb1e653692a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    126 schema:name Animals
    127 rdf:type schema:DefinedTerm
    128 N2444e90e0703443c820bedd29332c078 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    129 schema:name DNA-Binding Proteins
    130 rdf:type schema:DefinedTerm
    131 N32781423ec4849638a9e7b124b473bed schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    132 schema:name Monensin
    133 rdf:type schema:DefinedTerm
    134 N38b4fd98458643cd9edb891caf0b48c2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    135 schema:name Membrane Proteins
    136 rdf:type schema:DefinedTerm
    137 N3bbc9985c06b4aceb1333e815dc2f48e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    138 schema:name Molecular Sequence Data
    139 rdf:type schema:DefinedTerm
    140 N3ee21b5db796442a8487119ed38c0908 schema:name Springer Nature - SN SciGraph project
    141 rdf:type schema:Organization
    142 N4023dc2669d84c4cbb51611a73f743cb schema:issueNumber 6683
    143 rdf:type schema:PublicationIssue
    144 N42eb83074a1b43b19994276499fdb92f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    145 schema:name Promoter Regions, Genetic
    146 rdf:type schema:DefinedTerm
    147 N500e5715526e4522b27f87ba3d12481f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    148 schema:name Receptor, Notch1
    149 rdf:type schema:DefinedTerm
    150 N545a143519414cc5bf750021533a782f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    151 schema:name Cell Line
    152 rdf:type schema:DefinedTerm
    153 N5c5bafd80b39423da333296b57241dcb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    154 schema:name Mice
    155 rdf:type schema:DefinedTerm
    156 N5f5583a6b4da4865acfa21d6e06bb576 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    157 schema:name Basic Helix-Loop-Helix Transcription Factors
    158 rdf:type schema:DefinedTerm
    159 N60f4aa401cf748b6a77a3ca940a16ebc schema:name dimensions_id
    160 schema:value pub.1041325757
    161 rdf:type schema:PropertyValue
    162 N6a4b0b1a3fc64991b81448ebc18695ec rdf:first sg:person.0660157721.51
    163 rdf:rest rdf:nil
    164 N740ce2082a864331a2bc3d173b92aa24 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    165 schema:name Cyclopentanes
    166 rdf:type schema:DefinedTerm
    167 N745a55cc90094800a9c322287d4064af schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    168 schema:name Gene Expression Regulation
    169 rdf:type schema:DefinedTerm
    170 N76657cf488594473b4d793a496d6344b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    171 schema:name Cell Nucleus
    172 rdf:type schema:DefinedTerm
    173 N7697ab7190844af2a62369dda4e39af0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    174 schema:name Mutagenesis
    175 rdf:type schema:DefinedTerm
    176 N7c42919fe22b4399926d3cd85de4ac67 schema:name doi
    177 schema:value 10.1038/30756
    178 rdf:type schema:PropertyValue
    179 N83f5e5f238da48d8ab5b15d843d5fd7a schema:name pubmed_id
    180 schema:value 9620803
    181 rdf:type schema:PropertyValue
    182 N85e8a9ece7d94f2797a7b175283bec84 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    183 schema:name 3T3 Cells
    184 rdf:type schema:DefinedTerm
    185 N8d3cc4e918ae4961b473d3ef6b35067a schema:affiliation grid-institutes:grid.4367.6
    186 schema:familyName Kisslinger
    187 schema:givenName Jeffrey A.
    188 rdf:type schema:Person
    189 N95221ca66ff145e2b4eb2cbec16232c3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    190 schema:name Golgi Apparatus
    191 rdf:type schema:DefinedTerm
    192 N96ec738c1bca4b1b9db3c15d58422d14 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    193 schema:name Peptide Fragments
    194 rdf:type schema:DefinedTerm
    195 N9b52ed9365324c43a132f2e971a1517e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    196 schema:name Genes, Reporter
    197 rdf:type schema:DefinedTerm
    198 N9bc130cad9784d6dae8b4470d80c64e2 rdf:first sg:person.0742772124.34
    199 rdf:rest N157721ce68774108a6c62581177eda6f
    200 Naa06a90b318e4e15b94757fb5c4541b1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    201 schema:name Brefeldin A
    202 rdf:type schema:DefinedTerm
    203 Naa8f905c08d9439c916f6af8b9923315 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    204 schema:name Homeodomain Proteins
    205 rdf:type schema:DefinedTerm
    206 Nac33910c96ce482db48ad0753ee77e29 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    207 schema:name Receptors, Cell Surface
    208 rdf:type schema:DefinedTerm
    209 Naf9ec3ee13d949d3a6f25efbec0a34c2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    210 schema:name Protein Processing, Post-Translational
    211 rdf:type schema:DefinedTerm
    212 Nc8b36465c98b4681977233bc49e914e2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    213 schema:name Transcription Factors
    214 rdf:type schema:DefinedTerm
    215 Nd25b88ead06f4066ba3a9c33ed235628 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    216 schema:name Amino Acid Sequence
    217 rdf:type schema:DefinedTerm
    218 Ne0218dd1df834365be901ae1e8427f78 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    219 schema:name Signal Transduction
    220 rdf:type schema:DefinedTerm
    221 Ne0e919b34ef645d49b8ec2e9e6cc67a8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    222 schema:name Ligands
    223 rdf:type schema:DefinedTerm
    224 Nf42a56d19ccf4c2ca7704485b8e66d7d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    225 schema:name Transfection
    226 rdf:type schema:DefinedTerm
    227 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
    228 schema:name Biological Sciences
    229 rdf:type schema:DefinedTerm
    230 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
    231 schema:name Biochemistry and Cell Biology
    232 rdf:type schema:DefinedTerm
    233 sg:journal.1018957 schema:issn 0028-0836
    234 1476-4687
    235 schema:name Nature
    236 schema:publisher Springer Nature
    237 rdf:type schema:Periodical
    238 sg:person.0660157721.51 schema:affiliation grid-institutes:grid.4367.6
    239 schema:familyName Kopan
    240 schema:givenName Raphael
    241 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0660157721.51
    242 rdf:type schema:Person
    243 sg:person.0742772124.34 schema:affiliation grid-institutes:grid.4367.6
    244 schema:familyName Schroeter
    245 schema:givenName Eric H.
    246 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0742772124.34
    247 rdf:type schema:Person
    248 sg:pub.10.1038/377355a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019765251
    249 https://doi.org/10.1038/377355a0
    250 rdf:type schema:CreativeWork
    251 sg:pub.10.1038/ng0797-212 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044650583
    252 https://doi.org/10.1038/ng0797-212
    253 rdf:type schema:CreativeWork
    254 grid-institutes:grid.4367.6 schema:alternateName Division of Dermatology and the Department of Molecular Biology and Pharmacology, Washington University, Box 8123, 4940 Parkview Place, 63110, St Louis, Missouri, USA
    255 schema:name Division of Dermatology and the Department of Molecular Biology and Pharmacology, Washington University, Box 8123, 4940 Parkview Place, 63110, St Louis, Missouri, USA
    256 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...