β-Catenin regulates expression of cyclin D1 in colon carcinoma cells View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1999-04

AUTHORS

Osamu Tetsu, Frank McCormick

ABSTRACT

Mutations in the adenomatous polyposis coli (APC) tumour-suppressor gene occur in most human colon cancers. Loss of functional APC protein results in the accumulation of beta-catenin. Mutant forms of beta-catenin have been discovered in colon cancers that retain wild-type APC genes, and also in melanomas, medulloblastomas, prostate cancer and gastric and hepatocellular carcinomas. The accumulation of beta-catenin activates genes that are responsive to transcription factors of the TCF/LEF family, with which beta-catenin interacts. Here we show that beta-catenin activates transcription from the cyclin D1 promoter, and that sequences within the promoter that are related to consensus TCF/LEF-binding sites are necessary for activation. The oncoprotein p21ras further activates transcription of the cyclin D1 gene, through sites within the promoter that bind the transcriptional regulators Ets or CREB. Cells expressing mutant beta-catenin produce high levels of cyclin D1 messenger RNA and protein constitutively. Furthermore, expression of a dominant-negative form of TCF in colon-cancer cells strongly inhibits expression of cyclin D1 without affecting expression of cyclin D2, cyclin E, or cyclin-dependent kinases 2, 4 or 6. This dominant-negative TCF causes cells to arrest in the G1 phase of the cell cycle; this phenotype can be rescued by expression of cyclin D1 under the cytomegalovirus promoter. Abnormal levels of beta-catenin may therefore contribute to neoplastic transformation by causing accumulation of cyclin D1. More... »

PAGES

422-426

References to SciGraph publications

Journal

TITLE

Nature

ISSUE

6726

VOLUME

398

Related Patents

  • Antibodies That Bind Specifically To Phosphorylated Β-Catenin
  • Disc-1 Pathway Activators In The Control Of Neurogenesis
  • Compositions And Methods For Treating And Diagnosing Cancer
  • Compositions And Methods For Treating And Diagnosing Cancer
  • Anti-Rspo1 Antibodies And Uses Thereof
  • Compositions And Methods For Treating And Diagnosing Cancer
  • Compositions And Methods For Treating And Diagnosing Cancer
  • Reverse-Turn Mimetics And Method Relating Thereto
  • Alpha Helix Mimetic Compositions For Treating Cancer And Other Cbp/Catenin-Mediated Diseases And Conditions
  • Anti-Rspo2 Antibodies And Uses Thereof
  • Isolated Stra6 Polypeptides
  • Therapeutic Treatment Of Chronic Obstructive Pulmonary Disease
  • Treatment Of Dermal Fibrosis
  • Alpha Helix Mimetics And Methods Relating Thereto
  • Reverse-Turn Mimetics And Method Relating Thereto
  • Pygopus In Diagnosis And Treatment Of Cancer
  • Telomerase Reverse Transcriptase For Protection Against Ageing
  • Gene Expression Using T Cell Factor Responsive Element
  • Compositions And Methods For Treating And Diagnosing Cancer
  • Egfr-Based Peptides
  • Antibodies To Stra6 Polypeptides
  • Egfr-Based Inhibitor Peptides For Combinatorial Inactivation Of Erbb1, Erbb2, And Erbb3
  • Promoters For Regulated Gene Expression
  • Therapeutic Peptides For The Treatment Of Metastatic Cancer
  • Anti-Rspo2 Antibodies
  • Compositions And Methods For Treating And Diagnosing Cancer
  • Modulation Of Beta-Catenin Coactivator Interactions To Effect Stem Cell Growth Or Differentiation
  • Therapeutic Peptides For The Treatment Of Metastatic Cancer
  • Improved Cancer Therapy Based On Tumor Associated Antigens Derived From Cyclin D1
  • Stra6 Polypeptides
  • Anti-Rspo1 Antibodies
  • Rspo3 Binding Agents And Uses Thereof
  • Therapeutic Treatment Of Chronic Obstructive Pulmonary Disease
  • Anti-Fzd10 Monoclonal Antibodies And Methods For Their Use
  • Agents For Treating Human Illnesses Based On Β-Catenin, And The Production And Use Thereof
  • Tcf Responsive Element
  • Rspo3 Binding Agents And Uses Thereof
  • Anti-Fzd10 Monoclonal Antibodies And Methods For Their Use
  • Method Of Detecting Phosphorylation State Of Beta-Catenin
  • Telomerase Reverse Transcriptase For Protection Against Ageing
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/18884

    DOI

    http://dx.doi.org/10.1038/18884

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1037595361

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/10201372


    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/2008/0601", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biochemistry and Cell Biology", 
            "type": "DefinedTerm"
          }, 
          {
            "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"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Binding Sites", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Blotting, Western", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Division", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Colonic Neoplasms", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Consensus Sequence", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cyclin D1", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cytoskeletal Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "G1 Phase", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Gene Expression Regulation, Neoplastic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "HeLa Cells", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Luciferases", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mutagenesis, Site-Directed", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Promoter Regions, Genetic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Recombinant Fusion Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Reverse Transcriptase Polymerase Chain Reaction", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "TCF Transcription Factors", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Trans-Activators", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Transcription Factor 7-Like 2 Protein", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Transcription Factors", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Transcription, Genetic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Tumor Cells, Cultured", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "beta Catenin", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "ras Proteins", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "University of California, San Francisco", 
              "id": "https://www.grid.ac/institutes/grid.266102.1", 
              "name": [
                "University of California, San Francisco, School of Medicine, Cancer Research Institute, San Francisco, California 94143-0128, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Tetsu", 
            "givenName": "Osamu", 
            "id": "sg:person.01221550640.00", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01221550640.00"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of California, San Francisco", 
              "id": "https://www.grid.ac/institutes/grid.266102.1", 
              "name": [
                "University of California, San Francisco, School of Medicine, Cancer Research Institute, San Francisco, California 94143-0128, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "McCormick", 
            "givenName": "Frank", 
            "id": "sg:person.01231273635.32", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01231273635.32"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "https://doi.org/10.1126/science.275.5307.1787", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002102308"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/382638a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002681668", 
              "https://doi.org/10.1038/382638a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.270.40.23589", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006951784"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1053/gast.1996.v110.pm8608874", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010278979"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1101/gad.11.18.2359", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010810686"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.95.15.8847", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1011845656"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1101/gad.9.8.995", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014221446"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0092-8674(00)81333-1", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014745301"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1101/gad.7.8.1559", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015564012"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1006/dbio.1997.8797", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016976945"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/gcc.2870070205", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1017479370"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0925-4773(96)00597-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024662383"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.272.16.10859", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1028441571"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1128/mcb.15.3.1175", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033772704"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0092-8674(00)80112-9", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033973380"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0092-8674(00)81925-x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039229691"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0092-8674(00)81924-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041383393"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.281.5382.1509", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042662127"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.92.7.3046", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1052633521"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0167-5699(96)10019-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1052739111"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.275.5307.1784", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062556119"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.275.5307.1790", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062556120"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1083027645", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1083073978", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1083226541", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1083267400", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1083280356", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1083280357", 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "1999-04", 
        "datePublishedReg": "1999-04-01", 
        "description": "Mutations in the adenomatous polyposis coli (APC) tumour-suppressor gene occur in most human colon cancers. Loss of functional APC protein results in the accumulation of beta-catenin. Mutant forms of beta-catenin have been discovered in colon cancers that retain wild-type APC genes, and also in melanomas, medulloblastomas, prostate cancer and gastric and hepatocellular carcinomas. The accumulation of beta-catenin activates genes that are responsive to transcription factors of the TCF/LEF family, with which beta-catenin interacts. Here we show that beta-catenin activates transcription from the cyclin D1 promoter, and that sequences within the promoter that are related to consensus TCF/LEF-binding sites are necessary for activation. The oncoprotein p21ras further activates transcription of the cyclin D1 gene, through sites within the promoter that bind the transcriptional regulators Ets or CREB. Cells expressing mutant beta-catenin produce high levels of cyclin D1 messenger RNA and protein constitutively. Furthermore, expression of a dominant-negative form of TCF in colon-cancer cells strongly inhibits expression of cyclin D1 without affecting expression of cyclin D2, cyclin E, or cyclin-dependent kinases 2, 4 or 6. This dominant-negative TCF causes cells to arrest in the G1 phase of the cell cycle; this phenotype can be rescued by expression of cyclin D1 under the cytomegalovirus promoter. Abnormal levels of beta-catenin may therefore contribute to neoplastic transformation by causing accumulation of cyclin D1.", 
        "genre": "research_article", 
        "id": "sg:pub.10.1038/18884", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": false, 
        "isPartOf": [
          {
            "id": "sg:journal.1018957", 
            "issn": [
              "0090-0028", 
              "1476-4687"
            ], 
            "name": "Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "6726", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "398"
          }
        ], 
        "name": "\u03b2-Catenin regulates expression of cyclin D1 in colon carcinoma cells", 
        "pagination": "422-426", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "b31766741b65002067067213319a06e500557870754a35305c1a6f201dd33c30"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "10201372"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "0410462"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/18884"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1037595361"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/18884", 
          "https://app.dimensions.ai/details/publication/pub.1037595361"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-11T12:25", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000362_0000000362/records_87106_00000001.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "http://www.nature.com/articles/18884"
      }
    ]
     

    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.10.1038/18884'

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

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/18884'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/18884'

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

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/18884'


     

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

    251 TRIPLES      21 PREDICATES      81 URIs      45 LITERALS      33 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/18884 schema:about N03b6485c45d1488ca3424a779bffea27
    2 N0c066325451b4fa98146c607935f2e01
    3 N1625970f9c57426c9c1cdc72bc131d5a
    4 N2944d097fe214966b879d13ddf6483ce
    5 N350bbde120884d70bfdb286820a0eaf8
    6 N350f4c5a202441898525bf2d5c24ada8
    7 N5717deb472ec4283bce18032491fe72e
    8 N6a179eb70fca465ea1d56e15b8ce5c0e
    9 N6cc5fa902ef2416a8fc3e83a3760c15a
    10 N7180970d39044fe18409f79ccd7cc3d2
    11 N868db758049e4b81b48baa9b9ab84dc3
    12 N96ef75babae24b289e0e85d8d7d32065
    13 N9a1e0d7a3dc8499b996bed980f6c2a62
    14 Na18e4d20b256433bb2927dcd94b62f62
    15 Nb5e3aab424894d53add67b16d2dde30a
    16 Nb646871ea27649f7ab510afb530c3348
    17 Nbde43c76020848aab82cc3b7e9271ca3
    18 Nc15fe96d9932478a8beb690746087e5a
    19 Nc72ab827bdba4f908f9fb352ec71faba
    20 Nc7d3220b053248f4a0af38cc1df89572
    21 Nc86a3700d0e045d08ec6f7d87a57f330
    22 Ncd2f2474bbec478b8336222b7575a09e
    23 Nedc4647861df40218fd0e714b88c1ce3
    24 Nfadb88d02114490ab7e7f2723e5e2333
    25 anzsrc-for:06
    26 anzsrc-for:0601
    27 schema:author N6ccfed39e9924b8aaeb9260bcfb4e011
    28 schema:citation sg:pub.10.1038/382638a0
    29 https://app.dimensions.ai/details/publication/pub.1083027645
    30 https://app.dimensions.ai/details/publication/pub.1083073978
    31 https://app.dimensions.ai/details/publication/pub.1083226541
    32 https://app.dimensions.ai/details/publication/pub.1083267400
    33 https://app.dimensions.ai/details/publication/pub.1083280356
    34 https://app.dimensions.ai/details/publication/pub.1083280357
    35 https://doi.org/10.1002/gcc.2870070205
    36 https://doi.org/10.1006/dbio.1997.8797
    37 https://doi.org/10.1016/0167-5699(96)10019-0
    38 https://doi.org/10.1016/0925-4773(96)00597-7
    39 https://doi.org/10.1016/s0092-8674(00)80112-9
    40 https://doi.org/10.1016/s0092-8674(00)81333-1
    41 https://doi.org/10.1016/s0092-8674(00)81924-8
    42 https://doi.org/10.1016/s0092-8674(00)81925-x
    43 https://doi.org/10.1053/gast.1996.v110.pm8608874
    44 https://doi.org/10.1073/pnas.92.7.3046
    45 https://doi.org/10.1073/pnas.95.15.8847
    46 https://doi.org/10.1074/jbc.270.40.23589
    47 https://doi.org/10.1074/jbc.272.16.10859
    48 https://doi.org/10.1101/gad.11.18.2359
    49 https://doi.org/10.1101/gad.7.8.1559
    50 https://doi.org/10.1101/gad.9.8.995
    51 https://doi.org/10.1126/science.275.5307.1784
    52 https://doi.org/10.1126/science.275.5307.1787
    53 https://doi.org/10.1126/science.275.5307.1790
    54 https://doi.org/10.1126/science.281.5382.1509
    55 https://doi.org/10.1128/mcb.15.3.1175
    56 schema:datePublished 1999-04
    57 schema:datePublishedReg 1999-04-01
    58 schema:description Mutations in the adenomatous polyposis coli (APC) tumour-suppressor gene occur in most human colon cancers. Loss of functional APC protein results in the accumulation of beta-catenin. Mutant forms of beta-catenin have been discovered in colon cancers that retain wild-type APC genes, and also in melanomas, medulloblastomas, prostate cancer and gastric and hepatocellular carcinomas. The accumulation of beta-catenin activates genes that are responsive to transcription factors of the TCF/LEF family, with which beta-catenin interacts. Here we show that beta-catenin activates transcription from the cyclin D1 promoter, and that sequences within the promoter that are related to consensus TCF/LEF-binding sites are necessary for activation. The oncoprotein p21ras further activates transcription of the cyclin D1 gene, through sites within the promoter that bind the transcriptional regulators Ets or CREB. Cells expressing mutant beta-catenin produce high levels of cyclin D1 messenger RNA and protein constitutively. Furthermore, expression of a dominant-negative form of TCF in colon-cancer cells strongly inhibits expression of cyclin D1 without affecting expression of cyclin D2, cyclin E, or cyclin-dependent kinases 2, 4 or 6. This dominant-negative TCF causes cells to arrest in the G1 phase of the cell cycle; this phenotype can be rescued by expression of cyclin D1 under the cytomegalovirus promoter. Abnormal levels of beta-catenin may therefore contribute to neoplastic transformation by causing accumulation of cyclin D1.
    59 schema:genre research_article
    60 schema:inLanguage en
    61 schema:isAccessibleForFree false
    62 schema:isPartOf N31d2baf87645486c8103db579e641e5f
    63 N3fa0c998acec473da93a259b77ff881e
    64 sg:journal.1018957
    65 schema:name β-Catenin regulates expression of cyclin D1 in colon carcinoma cells
    66 schema:pagination 422-426
    67 schema:productId N080253b821ab4a4fac620494b19a6ca8
    68 N551a46b9c8874c8f9f4614c23364cb46
    69 N75198da34b7a4894acdecdbb097292a8
    70 N902e0d3895604bc988f0f1d1dbb6a19e
    71 Ne7f21a1144bb4dd098547a3b28e8d64e
    72 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037595361
    73 https://doi.org/10.1038/18884
    74 schema:sdDatePublished 2019-04-11T12:25
    75 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    76 schema:sdPublisher Nc1223d7416994ed6a0b77aee476a6121
    77 schema:url http://www.nature.com/articles/18884
    78 sgo:license sg:explorer/license/
    79 sgo:sdDataset articles
    80 rdf:type schema:ScholarlyArticle
    81 N0221d6cd347947f8a85c4a044a81e63d rdf:first sg:person.01231273635.32
    82 rdf:rest rdf:nil
    83 N03b6485c45d1488ca3424a779bffea27 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    84 schema:name Binding Sites
    85 rdf:type schema:DefinedTerm
    86 N080253b821ab4a4fac620494b19a6ca8 schema:name doi
    87 schema:value 10.1038/18884
    88 rdf:type schema:PropertyValue
    89 N0c066325451b4fa98146c607935f2e01 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    90 schema:name Recombinant Fusion Proteins
    91 rdf:type schema:DefinedTerm
    92 N1625970f9c57426c9c1cdc72bc131d5a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    93 schema:name HeLa Cells
    94 rdf:type schema:DefinedTerm
    95 N2944d097fe214966b879d13ddf6483ce schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    96 schema:name Cyclin D1
    97 rdf:type schema:DefinedTerm
    98 N31d2baf87645486c8103db579e641e5f schema:volumeNumber 398
    99 rdf:type schema:PublicationVolume
    100 N350bbde120884d70bfdb286820a0eaf8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    101 schema:name Consensus Sequence
    102 rdf:type schema:DefinedTerm
    103 N350f4c5a202441898525bf2d5c24ada8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    104 schema:name Luciferases
    105 rdf:type schema:DefinedTerm
    106 N3fa0c998acec473da93a259b77ff881e schema:issueNumber 6726
    107 rdf:type schema:PublicationIssue
    108 N551a46b9c8874c8f9f4614c23364cb46 schema:name pubmed_id
    109 schema:value 10201372
    110 rdf:type schema:PropertyValue
    111 N5717deb472ec4283bce18032491fe72e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    112 schema:name Blotting, Western
    113 rdf:type schema:DefinedTerm
    114 N6a179eb70fca465ea1d56e15b8ce5c0e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    115 schema:name ras Proteins
    116 rdf:type schema:DefinedTerm
    117 N6cc5fa902ef2416a8fc3e83a3760c15a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    118 schema:name Colonic Neoplasms
    119 rdf:type schema:DefinedTerm
    120 N6ccfed39e9924b8aaeb9260bcfb4e011 rdf:first sg:person.01221550640.00
    121 rdf:rest N0221d6cd347947f8a85c4a044a81e63d
    122 N7180970d39044fe18409f79ccd7cc3d2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    123 schema:name TCF Transcription Factors
    124 rdf:type schema:DefinedTerm
    125 N75198da34b7a4894acdecdbb097292a8 schema:name nlm_unique_id
    126 schema:value 0410462
    127 rdf:type schema:PropertyValue
    128 N868db758049e4b81b48baa9b9ab84dc3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    129 schema:name G1 Phase
    130 rdf:type schema:DefinedTerm
    131 N902e0d3895604bc988f0f1d1dbb6a19e schema:name readcube_id
    132 schema:value b31766741b65002067067213319a06e500557870754a35305c1a6f201dd33c30
    133 rdf:type schema:PropertyValue
    134 N96ef75babae24b289e0e85d8d7d32065 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    135 schema:name Cell Division
    136 rdf:type schema:DefinedTerm
    137 N9a1e0d7a3dc8499b996bed980f6c2a62 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    138 schema:name Tumor Cells, Cultured
    139 rdf:type schema:DefinedTerm
    140 Na18e4d20b256433bb2927dcd94b62f62 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    141 schema:name Transcription Factors
    142 rdf:type schema:DefinedTerm
    143 Nb5e3aab424894d53add67b16d2dde30a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    144 schema:name beta Catenin
    145 rdf:type schema:DefinedTerm
    146 Nb646871ea27649f7ab510afb530c3348 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    147 schema:name Gene Expression Regulation, Neoplastic
    148 rdf:type schema:DefinedTerm
    149 Nbde43c76020848aab82cc3b7e9271ca3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    150 schema:name Trans-Activators
    151 rdf:type schema:DefinedTerm
    152 Nc1223d7416994ed6a0b77aee476a6121 schema:name Springer Nature - SN SciGraph project
    153 rdf:type schema:Organization
    154 Nc15fe96d9932478a8beb690746087e5a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    155 schema:name Humans
    156 rdf:type schema:DefinedTerm
    157 Nc72ab827bdba4f908f9fb352ec71faba schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    158 schema:name Transcription Factor 7-Like 2 Protein
    159 rdf:type schema:DefinedTerm
    160 Nc7d3220b053248f4a0af38cc1df89572 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    161 schema:name Transcription, Genetic
    162 rdf:type schema:DefinedTerm
    163 Nc86a3700d0e045d08ec6f7d87a57f330 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    164 schema:name Reverse Transcriptase Polymerase Chain Reaction
    165 rdf:type schema:DefinedTerm
    166 Ncd2f2474bbec478b8336222b7575a09e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    167 schema:name Promoter Regions, Genetic
    168 rdf:type schema:DefinedTerm
    169 Ne7f21a1144bb4dd098547a3b28e8d64e schema:name dimensions_id
    170 schema:value pub.1037595361
    171 rdf:type schema:PropertyValue
    172 Nedc4647861df40218fd0e714b88c1ce3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    173 schema:name Cytoskeletal Proteins
    174 rdf:type schema:DefinedTerm
    175 Nfadb88d02114490ab7e7f2723e5e2333 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    176 schema:name Mutagenesis, Site-Directed
    177 rdf:type schema:DefinedTerm
    178 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
    179 schema:name Biological Sciences
    180 rdf:type schema:DefinedTerm
    181 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
    182 schema:name Biochemistry and Cell Biology
    183 rdf:type schema:DefinedTerm
    184 sg:journal.1018957 schema:issn 0090-0028
    185 1476-4687
    186 schema:name Nature
    187 rdf:type schema:Periodical
    188 sg:person.01221550640.00 schema:affiliation https://www.grid.ac/institutes/grid.266102.1
    189 schema:familyName Tetsu
    190 schema:givenName Osamu
    191 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01221550640.00
    192 rdf:type schema:Person
    193 sg:person.01231273635.32 schema:affiliation https://www.grid.ac/institutes/grid.266102.1
    194 schema:familyName McCormick
    195 schema:givenName Frank
    196 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01231273635.32
    197 rdf:type schema:Person
    198 sg:pub.10.1038/382638a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002681668
    199 https://doi.org/10.1038/382638a0
    200 rdf:type schema:CreativeWork
    201 https://app.dimensions.ai/details/publication/pub.1083027645 schema:CreativeWork
    202 https://app.dimensions.ai/details/publication/pub.1083073978 schema:CreativeWork
    203 https://app.dimensions.ai/details/publication/pub.1083226541 schema:CreativeWork
    204 https://app.dimensions.ai/details/publication/pub.1083267400 schema:CreativeWork
    205 https://app.dimensions.ai/details/publication/pub.1083280356 schema:CreativeWork
    206 https://app.dimensions.ai/details/publication/pub.1083280357 schema:CreativeWork
    207 https://doi.org/10.1002/gcc.2870070205 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017479370
    208 rdf:type schema:CreativeWork
    209 https://doi.org/10.1006/dbio.1997.8797 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016976945
    210 rdf:type schema:CreativeWork
    211 https://doi.org/10.1016/0167-5699(96)10019-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052739111
    212 rdf:type schema:CreativeWork
    213 https://doi.org/10.1016/0925-4773(96)00597-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024662383
    214 rdf:type schema:CreativeWork
    215 https://doi.org/10.1016/s0092-8674(00)80112-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033973380
    216 rdf:type schema:CreativeWork
    217 https://doi.org/10.1016/s0092-8674(00)81333-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014745301
    218 rdf:type schema:CreativeWork
    219 https://doi.org/10.1016/s0092-8674(00)81924-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041383393
    220 rdf:type schema:CreativeWork
    221 https://doi.org/10.1016/s0092-8674(00)81925-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1039229691
    222 rdf:type schema:CreativeWork
    223 https://doi.org/10.1053/gast.1996.v110.pm8608874 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010278979
    224 rdf:type schema:CreativeWork
    225 https://doi.org/10.1073/pnas.92.7.3046 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052633521
    226 rdf:type schema:CreativeWork
    227 https://doi.org/10.1073/pnas.95.15.8847 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011845656
    228 rdf:type schema:CreativeWork
    229 https://doi.org/10.1074/jbc.270.40.23589 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006951784
    230 rdf:type schema:CreativeWork
    231 https://doi.org/10.1074/jbc.272.16.10859 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028441571
    232 rdf:type schema:CreativeWork
    233 https://doi.org/10.1101/gad.11.18.2359 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010810686
    234 rdf:type schema:CreativeWork
    235 https://doi.org/10.1101/gad.7.8.1559 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015564012
    236 rdf:type schema:CreativeWork
    237 https://doi.org/10.1101/gad.9.8.995 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014221446
    238 rdf:type schema:CreativeWork
    239 https://doi.org/10.1126/science.275.5307.1784 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062556119
    240 rdf:type schema:CreativeWork
    241 https://doi.org/10.1126/science.275.5307.1787 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002102308
    242 rdf:type schema:CreativeWork
    243 https://doi.org/10.1126/science.275.5307.1790 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062556120
    244 rdf:type schema:CreativeWork
    245 https://doi.org/10.1126/science.281.5382.1509 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042662127
    246 rdf:type schema:CreativeWork
    247 https://doi.org/10.1128/mcb.15.3.1175 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033772704
    248 rdf:type schema:CreativeWork
    249 https://www.grid.ac/institutes/grid.266102.1 schema:alternateName University of California, San Francisco
    250 schema:name University of California, San Francisco, School of Medicine, Cancer Research Institute, San Francisco, California 94143-0128, USA
    251 rdf:type schema:Organization
     




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


    ...