Tissue-specific expression of an anti-proliferative hybrid transgene from the human smooth muscle α-actin promoter suppresses smooth muscle cell proliferation and ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2001-12

AUTHORS

KN Wills, T Mano, JB Avanzini, T Nguyen, D Antelman, RJ Gregory, RC Smith, K Walsh

ABSTRACT

The retinoblastoma protein (Rb), a key regulator of cell cycle progression, can bind the transcription factor E2F converting it from a positive transcriptional factor capable of driving cells into S phase into a negative complex which arrests cells in G1. We have created a potent transcriptional repressor of E2F-dependent transcription by fusing the C-terminal fragment of Rb (p56) to the DNA and DP1-binding domains of E2F. Because the expression of E2F/56 fusion protein from a constitutive promoter was incompatible with virus growth, adenovirus constructs were prepared where transgenes were expressed from a fragment of the smooth muscle alpha-actin (SMA) promoter. Immunoblot and beta-galactosidase staining demonstrated smooth muscle-specific expression of this transcriptional element in vitro. The SMA-p56 and SMA-E2F/p56 adenoviral constructs also induced G0/G1 cell cycle arrest specifically in smooth muscle cells. Following administration to rat tissues, the SMA-beta-galactosidase construct exhibited expression in balloon-injured carotid arteries, but not in liver, bladder or skeletal muscle. Local delivery of the SMA-E2F/p56 adenoviral construct to balloon-injured carotid arteries inhibited intimal hyperplasia. Our results demonstrate that local delivery of the SMA-E2F/p56 adenoviral construct can limit intimal hyperplasia in balloon-injured vessels, while avoiding toxicity that could occur from the dissemination and expression of the viral transgene. More... »

PAGES

3301603

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.gt.3301603

DOI

http://dx.doi.org/10.1038/sj.gt.3301603

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1004372937

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/11821938


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": "Actins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Adenoviridae", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Angioplasty, Balloon", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Animals", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Artificial Gene Fusion", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Carotid Arteries", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Cycle", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Cycle Proteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "DNA-Binding Proteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "E2F Transcription Factors", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Genetic Therapy", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Genetic Vectors", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Hyperplasia", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Muscle, Smooth, Vascular", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Rats", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Retinoblastoma Protein", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Transcription Factors", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Transgenes", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Tunica Intima", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "beta-Galactosidase", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "MSD (United States)", 
          "id": "https://www.grid.ac/institutes/grid.417993.1", 
          "name": [
            "Canji, Inc., San Diego, CA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wills", 
        "givenName": "KN", 
        "id": "sg:person.0677524007.29", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0677524007.29"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "St. Elizabeth's Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.240845.f", 
          "name": [
            "Division of Cardiovascular Research, Department of Medicine, St Elizabeth's Medical Center, Boston, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Mano", 
        "givenName": "T", 
        "id": "sg:person.0654073126.92", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0654073126.92"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "MSD (United States)", 
          "id": "https://www.grid.ac/institutes/grid.417993.1", 
          "name": [
            "Canji, Inc., San Diego, CA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Avanzini", 
        "givenName": "JB", 
        "id": "sg:person.01001205224.91", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01001205224.91"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "St. Elizabeth's Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.240845.f", 
          "name": [
            "Division of Cardiovascular Research, Department of Medicine, St Elizabeth's Medical Center, Boston, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Nguyen", 
        "givenName": "T", 
        "id": "sg:person.0765524524.41", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0765524524.41"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "MSD (United States)", 
          "id": "https://www.grid.ac/institutes/grid.417993.1", 
          "name": [
            "Canji, Inc., San Diego, CA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Antelman", 
        "givenName": "D", 
        "id": "sg:person.0662407635.72", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0662407635.72"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Sanofi (United States)", 
          "id": "https://www.grid.ac/institutes/grid.417555.7", 
          "name": [
            "Genzyme, Framingham, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Gregory", 
        "givenName": "RJ", 
        "id": "sg:person.014004074062.33", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014004074062.33"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "St. Elizabeth's Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.240845.f", 
          "name": [
            "Division of Cardiovascular Research, Department of Medicine, St Elizabeth's Medical Center, Boston, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Smith", 
        "givenName": "RC", 
        "id": "sg:person.012532604324.12", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012532604324.12"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "St. Elizabeth's Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.240845.f", 
          "name": [
            "Division of Cardiovascular Research, Department of Medicine, St Elizabeth's Medical Center, Boston, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Walsh", 
        "givenName": "K", 
        "id": "sg:person.0666727752.36", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0666727752.36"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1038/sj.onc.1201465", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002587427", 
          "https://doi.org/10.1038/sj.onc.1201465"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1201465", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002587427", 
          "https://doi.org/10.1038/sj.onc.1201465"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1161/01.res.84.7.852", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007847771"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/mcb.2.9.1044", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015185081"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.92.25.11544", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015664954"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/358259a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020237383", 
          "https://doi.org/10.1038/358259a0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1101/gad.6.6.953", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022410133"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1172/jci119611", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025655862"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/0022-1759(94)90267-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029036572"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/0022-1759(94)90267-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029036572"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.270.13.7631", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030501736"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nbt1196-1570", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031273317", 
          "https://doi.org/10.1038/nbt1196-1570"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.270.6.2460", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038758754"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejm199605023341809", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041888468"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/0735-1097(92)90259-p", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050459560"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/mcb.13.6.3384", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052357773"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/0378-1119(91)90140-7", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053025666"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/0378-1119(91)90140-7", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053025666"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1172/jci107470", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053383708"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1089/10430340050015987", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1059201973"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1089/hum.1994.5.9-1079", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1059271450"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.7824950", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1062649844"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.8248803", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1062653833"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1161/01.cir.95.8.1998", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1063338000"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1161/01.cir.96.6.1899", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1063338441"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/bf03401832", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1074747787", 
          "https://doi.org/10.1007/bf03401832"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1078618817", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1082012588", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1152/ajprenal.1995.268.4.f760", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1082485013"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1082929627", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1083038954", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1161/01.res.0000435858.35902.ea", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1083052851"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2001-12", 
    "datePublishedReg": "2001-12-01", 
    "description": "The retinoblastoma protein (Rb), a key regulator of cell cycle progression, can bind the transcription factor E2F converting it from a positive transcriptional factor capable of driving cells into S phase into a negative complex which arrests cells in G1. We have created a potent transcriptional repressor of E2F-dependent transcription by fusing the C-terminal fragment of Rb (p56) to the DNA and DP1-binding domains of E2F. Because the expression of E2F/56 fusion protein from a constitutive promoter was incompatible with virus growth, adenovirus constructs were prepared where transgenes were expressed from a fragment of the smooth muscle alpha-actin (SMA) promoter. Immunoblot and beta-galactosidase staining demonstrated smooth muscle-specific expression of this transcriptional element in vitro. The SMA-p56 and SMA-E2F/p56 adenoviral constructs also induced G0/G1 cell cycle arrest specifically in smooth muscle cells. Following administration to rat tissues, the SMA-beta-galactosidase construct exhibited expression in balloon-injured carotid arteries, but not in liver, bladder or skeletal muscle. Local delivery of the SMA-E2F/p56 adenoviral construct to balloon-injured carotid arteries inhibited intimal hyperplasia. Our results demonstrate that local delivery of the SMA-E2F/p56 adenoviral construct can limit intimal hyperplasia in balloon-injured vessels, while avoiding toxicity that could occur from the dissemination and expression of the viral transgene.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/sj.gt.3301603", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1105638", 
        "issn": [
          "0969-7128", 
          "1476-5462"
        ], 
        "name": "Gene Therapy", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "24", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "8"
      }
    ], 
    "name": "Tissue-specific expression of an anti-proliferative hybrid transgene from the human smooth muscle \u03b1-actin promoter suppresses smooth muscle cell proliferation and neointima formation", 
    "pagination": "3301603", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "14d61bb048e78d67f4002943f8c074e480895cbff0048c7a6221e2cb1c47375e"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "11821938"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "9421525"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/sj.gt.3301603"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1004372937"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/sj.gt.3301603", 
      "https://app.dimensions.ai/details/publication/pub.1004372937"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T12:06", 
    "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/v90/0000000360_0000000360/records_118335_00000000.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "http://www.nature.com/articles/3301603"
  }
]
 

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/sj.gt.3301603'

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/sj.gt.3301603'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/sj.gt.3301603'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/sj.gt.3301603'


 

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

295 TRIPLES      21 PREDICATES      79 URIs      42 LITERALS      30 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/sj.gt.3301603 schema:about N01d63c6499a24b9eb51be4ab34777079
2 N1223bb24184848388a0de258640a3ae1
3 N198474bd26da476d887f5f39abd5c7f4
4 N1e47a558af204f0e9671d7982d399a03
5 N256d38b4e1544234baa6b78a9d9bc4bf
6 N2935603944304dedb1211b20b3a57004
7 N2dc39bdb67804573a3931b21d779c4bb
8 N45b7b5396a514826a54b95cf987718ad
9 N503852d71b2141e08a2e89b3ac0f84d2
10 N652441b5cdc44905aded6b841d824451
11 N69df824f1fe94f1ea30a86bc97fb92f2
12 N72d45e46131949688b3441c0c7fdd16b
13 N7d1a2590398f4c459deab3f058214793
14 N8fa17149072f4ede9c706e33f98f0a98
15 Nb26a1da351fc43bb9c58bcf34dfa46e4
16 Nb8ad8494efd24f2e8faef1fa7d670576
17 Ncf3a4ab30d174a378528186dfbd88d39
18 Nd47e6e2520c34c18a35e66ee8d2bc1d9
19 Nde584ee6f4e0486c969450cd9d8ce602
20 Nde7de51ede9f4dbe8d72ee9fff9da5a4
21 Nef31facf37b047f589da6716cd9a33db
22 anzsrc-for:06
23 anzsrc-for:0601
24 schema:author Nf429413ae8fd4b8ab1e58296b1530aea
25 schema:citation sg:pub.10.1007/bf03401832
26 sg:pub.10.1038/358259a0
27 sg:pub.10.1038/nbt1196-1570
28 sg:pub.10.1038/sj.onc.1201465
29 https://app.dimensions.ai/details/publication/pub.1078618817
30 https://app.dimensions.ai/details/publication/pub.1082012588
31 https://app.dimensions.ai/details/publication/pub.1082929627
32 https://app.dimensions.ai/details/publication/pub.1083038954
33 https://doi.org/10.1016/0022-1759(94)90267-4
34 https://doi.org/10.1016/0378-1119(91)90140-7
35 https://doi.org/10.1016/0735-1097(92)90259-p
36 https://doi.org/10.1056/nejm199605023341809
37 https://doi.org/10.1073/pnas.92.25.11544
38 https://doi.org/10.1074/jbc.270.13.7631
39 https://doi.org/10.1074/jbc.270.6.2460
40 https://doi.org/10.1089/10430340050015987
41 https://doi.org/10.1089/hum.1994.5.9-1079
42 https://doi.org/10.1101/gad.6.6.953
43 https://doi.org/10.1126/science.7824950
44 https://doi.org/10.1126/science.8248803
45 https://doi.org/10.1128/mcb.13.6.3384
46 https://doi.org/10.1128/mcb.2.9.1044
47 https://doi.org/10.1152/ajprenal.1995.268.4.f760
48 https://doi.org/10.1161/01.cir.95.8.1998
49 https://doi.org/10.1161/01.cir.96.6.1899
50 https://doi.org/10.1161/01.res.0000435858.35902.ea
51 https://doi.org/10.1161/01.res.84.7.852
52 https://doi.org/10.1172/jci107470
53 https://doi.org/10.1172/jci119611
54 schema:datePublished 2001-12
55 schema:datePublishedReg 2001-12-01
56 schema:description The retinoblastoma protein (Rb), a key regulator of cell cycle progression, can bind the transcription factor E2F converting it from a positive transcriptional factor capable of driving cells into S phase into a negative complex which arrests cells in G1. We have created a potent transcriptional repressor of E2F-dependent transcription by fusing the C-terminal fragment of Rb (p56) to the DNA and DP1-binding domains of E2F. Because the expression of E2F/56 fusion protein from a constitutive promoter was incompatible with virus growth, adenovirus constructs were prepared where transgenes were expressed from a fragment of the smooth muscle alpha-actin (SMA) promoter. Immunoblot and beta-galactosidase staining demonstrated smooth muscle-specific expression of this transcriptional element in vitro. The SMA-p56 and SMA-E2F/p56 adenoviral constructs also induced G0/G1 cell cycle arrest specifically in smooth muscle cells. Following administration to rat tissues, the SMA-beta-galactosidase construct exhibited expression in balloon-injured carotid arteries, but not in liver, bladder or skeletal muscle. Local delivery of the SMA-E2F/p56 adenoviral construct to balloon-injured carotid arteries inhibited intimal hyperplasia. Our results demonstrate that local delivery of the SMA-E2F/p56 adenoviral construct can limit intimal hyperplasia in balloon-injured vessels, while avoiding toxicity that could occur from the dissemination and expression of the viral transgene.
57 schema:genre research_article
58 schema:inLanguage en
59 schema:isAccessibleForFree true
60 schema:isPartOf N4d05b7c05eaa4b09993d379d4100fd9f
61 N6030928dd6284b12bd77a90a7c6336ee
62 sg:journal.1105638
63 schema:name Tissue-specific expression of an anti-proliferative hybrid transgene from the human smooth muscle α-actin promoter suppresses smooth muscle cell proliferation and neointima formation
64 schema:pagination 3301603
65 schema:productId N0d537142fdf5412295b1d6bce82e6f49
66 N9c168b4d3a344c3ba39d93e8247d4561
67 Nb25fcfae6b8144698650a079b9b156f6
68 Ncab818b15fde4b14ba4ae79e9f814c73
69 Ne4e853e4854042cf91906274c07d9d88
70 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004372937
71 https://doi.org/10.1038/sj.gt.3301603
72 schema:sdDatePublished 2019-04-11T12:06
73 schema:sdLicense https://scigraph.springernature.com/explorer/license/
74 schema:sdPublisher Na7c236c7f42a416aa73a969f1dacdee2
75 schema:url http://www.nature.com/articles/3301603
76 sgo:license sg:explorer/license/
77 sgo:sdDataset articles
78 rdf:type schema:ScholarlyArticle
79 N01d63c6499a24b9eb51be4ab34777079 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
80 schema:name Angioplasty, Balloon
81 rdf:type schema:DefinedTerm
82 N057ac5968dcf4289aa4a045b291a853d rdf:first sg:person.014004074062.33
83 rdf:rest Na2ca5236ee134b0fa6c76072825a0c85
84 N0d537142fdf5412295b1d6bce82e6f49 schema:name dimensions_id
85 schema:value pub.1004372937
86 rdf:type schema:PropertyValue
87 N1223bb24184848388a0de258640a3ae1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
88 schema:name Genetic Therapy
89 rdf:type schema:DefinedTerm
90 N198474bd26da476d887f5f39abd5c7f4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
91 schema:name Cell Cycle
92 rdf:type schema:DefinedTerm
93 N1e47a558af204f0e9671d7982d399a03 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
94 schema:name Genetic Vectors
95 rdf:type schema:DefinedTerm
96 N256d38b4e1544234baa6b78a9d9bc4bf schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
97 schema:name Muscle, Smooth, Vascular
98 rdf:type schema:DefinedTerm
99 N2935603944304dedb1211b20b3a57004 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
100 schema:name Transcription Factors
101 rdf:type schema:DefinedTerm
102 N2dc39bdb67804573a3931b21d779c4bb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
103 schema:name Animals
104 rdf:type schema:DefinedTerm
105 N45b7b5396a514826a54b95cf987718ad schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
106 schema:name Artificial Gene Fusion
107 rdf:type schema:DefinedTerm
108 N4d05b7c05eaa4b09993d379d4100fd9f schema:issueNumber 24
109 rdf:type schema:PublicationIssue
110 N503852d71b2141e08a2e89b3ac0f84d2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
111 schema:name Rats
112 rdf:type schema:DefinedTerm
113 N6030928dd6284b12bd77a90a7c6336ee schema:volumeNumber 8
114 rdf:type schema:PublicationVolume
115 N635fd60d5fda4fedb999879d07d79301 rdf:first sg:person.0666727752.36
116 rdf:rest rdf:nil
117 N652441b5cdc44905aded6b841d824451 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
118 schema:name Tunica Intima
119 rdf:type schema:DefinedTerm
120 N69df824f1fe94f1ea30a86bc97fb92f2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
121 schema:name Transgenes
122 rdf:type schema:DefinedTerm
123 N72d45e46131949688b3441c0c7fdd16b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
124 schema:name Cell Cycle Proteins
125 rdf:type schema:DefinedTerm
126 N7d1a2590398f4c459deab3f058214793 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
127 schema:name Actins
128 rdf:type schema:DefinedTerm
129 N8ca8c459f33e4c3ea1410f8e1373d970 rdf:first sg:person.0662407635.72
130 rdf:rest N057ac5968dcf4289aa4a045b291a853d
131 N8fa17149072f4ede9c706e33f98f0a98 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
132 schema:name Humans
133 rdf:type schema:DefinedTerm
134 N9c168b4d3a344c3ba39d93e8247d4561 schema:name readcube_id
135 schema:value 14d61bb048e78d67f4002943f8c074e480895cbff0048c7a6221e2cb1c47375e
136 rdf:type schema:PropertyValue
137 Na2ca5236ee134b0fa6c76072825a0c85 rdf:first sg:person.012532604324.12
138 rdf:rest N635fd60d5fda4fedb999879d07d79301
139 Na7c236c7f42a416aa73a969f1dacdee2 schema:name Springer Nature - SN SciGraph project
140 rdf:type schema:Organization
141 Nb19e523ed3b840e092d272641adf1d76 rdf:first sg:person.0654073126.92
142 rdf:rest Nf024427d913f4c278d78e4ee6cd282d7
143 Nb25fcfae6b8144698650a079b9b156f6 schema:name pubmed_id
144 schema:value 11821938
145 rdf:type schema:PropertyValue
146 Nb26a1da351fc43bb9c58bcf34dfa46e4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
147 schema:name DNA-Binding Proteins
148 rdf:type schema:DefinedTerm
149 Nb8ad8494efd24f2e8faef1fa7d670576 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
150 schema:name Carotid Arteries
151 rdf:type schema:DefinedTerm
152 Ncab818b15fde4b14ba4ae79e9f814c73 schema:name doi
153 schema:value 10.1038/sj.gt.3301603
154 rdf:type schema:PropertyValue
155 Nce0a5251dc8a46c49ce573b864069bae rdf:first sg:person.0765524524.41
156 rdf:rest N8ca8c459f33e4c3ea1410f8e1373d970
157 Ncf3a4ab30d174a378528186dfbd88d39 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
158 schema:name Hyperplasia
159 rdf:type schema:DefinedTerm
160 Nd47e6e2520c34c18a35e66ee8d2bc1d9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
161 schema:name beta-Galactosidase
162 rdf:type schema:DefinedTerm
163 Nde584ee6f4e0486c969450cd9d8ce602 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
164 schema:name Retinoblastoma Protein
165 rdf:type schema:DefinedTerm
166 Nde7de51ede9f4dbe8d72ee9fff9da5a4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
167 schema:name E2F Transcription Factors
168 rdf:type schema:DefinedTerm
169 Ne4e853e4854042cf91906274c07d9d88 schema:name nlm_unique_id
170 schema:value 9421525
171 rdf:type schema:PropertyValue
172 Nef31facf37b047f589da6716cd9a33db schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
173 schema:name Adenoviridae
174 rdf:type schema:DefinedTerm
175 Nf024427d913f4c278d78e4ee6cd282d7 rdf:first sg:person.01001205224.91
176 rdf:rest Nce0a5251dc8a46c49ce573b864069bae
177 Nf429413ae8fd4b8ab1e58296b1530aea rdf:first sg:person.0677524007.29
178 rdf:rest Nb19e523ed3b840e092d272641adf1d76
179 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
180 schema:name Biological Sciences
181 rdf:type schema:DefinedTerm
182 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
183 schema:name Biochemistry and Cell Biology
184 rdf:type schema:DefinedTerm
185 sg:journal.1105638 schema:issn 0969-7128
186 1476-5462
187 schema:name Gene Therapy
188 rdf:type schema:Periodical
189 sg:person.01001205224.91 schema:affiliation https://www.grid.ac/institutes/grid.417993.1
190 schema:familyName Avanzini
191 schema:givenName JB
192 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01001205224.91
193 rdf:type schema:Person
194 sg:person.012532604324.12 schema:affiliation https://www.grid.ac/institutes/grid.240845.f
195 schema:familyName Smith
196 schema:givenName RC
197 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012532604324.12
198 rdf:type schema:Person
199 sg:person.014004074062.33 schema:affiliation https://www.grid.ac/institutes/grid.417555.7
200 schema:familyName Gregory
201 schema:givenName RJ
202 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014004074062.33
203 rdf:type schema:Person
204 sg:person.0654073126.92 schema:affiliation https://www.grid.ac/institutes/grid.240845.f
205 schema:familyName Mano
206 schema:givenName T
207 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0654073126.92
208 rdf:type schema:Person
209 sg:person.0662407635.72 schema:affiliation https://www.grid.ac/institutes/grid.417993.1
210 schema:familyName Antelman
211 schema:givenName D
212 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0662407635.72
213 rdf:type schema:Person
214 sg:person.0666727752.36 schema:affiliation https://www.grid.ac/institutes/grid.240845.f
215 schema:familyName Walsh
216 schema:givenName K
217 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0666727752.36
218 rdf:type schema:Person
219 sg:person.0677524007.29 schema:affiliation https://www.grid.ac/institutes/grid.417993.1
220 schema:familyName Wills
221 schema:givenName KN
222 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0677524007.29
223 rdf:type schema:Person
224 sg:person.0765524524.41 schema:affiliation https://www.grid.ac/institutes/grid.240845.f
225 schema:familyName Nguyen
226 schema:givenName T
227 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0765524524.41
228 rdf:type schema:Person
229 sg:pub.10.1007/bf03401832 schema:sameAs https://app.dimensions.ai/details/publication/pub.1074747787
230 https://doi.org/10.1007/bf03401832
231 rdf:type schema:CreativeWork
232 sg:pub.10.1038/358259a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020237383
233 https://doi.org/10.1038/358259a0
234 rdf:type schema:CreativeWork
235 sg:pub.10.1038/nbt1196-1570 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031273317
236 https://doi.org/10.1038/nbt1196-1570
237 rdf:type schema:CreativeWork
238 sg:pub.10.1038/sj.onc.1201465 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002587427
239 https://doi.org/10.1038/sj.onc.1201465
240 rdf:type schema:CreativeWork
241 https://app.dimensions.ai/details/publication/pub.1078618817 schema:CreativeWork
242 https://app.dimensions.ai/details/publication/pub.1082012588 schema:CreativeWork
243 https://app.dimensions.ai/details/publication/pub.1082929627 schema:CreativeWork
244 https://app.dimensions.ai/details/publication/pub.1083038954 schema:CreativeWork
245 https://doi.org/10.1016/0022-1759(94)90267-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029036572
246 rdf:type schema:CreativeWork
247 https://doi.org/10.1016/0378-1119(91)90140-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053025666
248 rdf:type schema:CreativeWork
249 https://doi.org/10.1016/0735-1097(92)90259-p schema:sameAs https://app.dimensions.ai/details/publication/pub.1050459560
250 rdf:type schema:CreativeWork
251 https://doi.org/10.1056/nejm199605023341809 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041888468
252 rdf:type schema:CreativeWork
253 https://doi.org/10.1073/pnas.92.25.11544 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015664954
254 rdf:type schema:CreativeWork
255 https://doi.org/10.1074/jbc.270.13.7631 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030501736
256 rdf:type schema:CreativeWork
257 https://doi.org/10.1074/jbc.270.6.2460 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038758754
258 rdf:type schema:CreativeWork
259 https://doi.org/10.1089/10430340050015987 schema:sameAs https://app.dimensions.ai/details/publication/pub.1059201973
260 rdf:type schema:CreativeWork
261 https://doi.org/10.1089/hum.1994.5.9-1079 schema:sameAs https://app.dimensions.ai/details/publication/pub.1059271450
262 rdf:type schema:CreativeWork
263 https://doi.org/10.1101/gad.6.6.953 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022410133
264 rdf:type schema:CreativeWork
265 https://doi.org/10.1126/science.7824950 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062649844
266 rdf:type schema:CreativeWork
267 https://doi.org/10.1126/science.8248803 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062653833
268 rdf:type schema:CreativeWork
269 https://doi.org/10.1128/mcb.13.6.3384 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052357773
270 rdf:type schema:CreativeWork
271 https://doi.org/10.1128/mcb.2.9.1044 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015185081
272 rdf:type schema:CreativeWork
273 https://doi.org/10.1152/ajprenal.1995.268.4.f760 schema:sameAs https://app.dimensions.ai/details/publication/pub.1082485013
274 rdf:type schema:CreativeWork
275 https://doi.org/10.1161/01.cir.95.8.1998 schema:sameAs https://app.dimensions.ai/details/publication/pub.1063338000
276 rdf:type schema:CreativeWork
277 https://doi.org/10.1161/01.cir.96.6.1899 schema:sameAs https://app.dimensions.ai/details/publication/pub.1063338441
278 rdf:type schema:CreativeWork
279 https://doi.org/10.1161/01.res.0000435858.35902.ea schema:sameAs https://app.dimensions.ai/details/publication/pub.1083052851
280 rdf:type schema:CreativeWork
281 https://doi.org/10.1161/01.res.84.7.852 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007847771
282 rdf:type schema:CreativeWork
283 https://doi.org/10.1172/jci107470 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053383708
284 rdf:type schema:CreativeWork
285 https://doi.org/10.1172/jci119611 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025655862
286 rdf:type schema:CreativeWork
287 https://www.grid.ac/institutes/grid.240845.f schema:alternateName St. Elizabeth's Medical Center
288 schema:name Division of Cardiovascular Research, Department of Medicine, St Elizabeth's Medical Center, Boston, MA, USA
289 rdf:type schema:Organization
290 https://www.grid.ac/institutes/grid.417555.7 schema:alternateName Sanofi (United States)
291 schema:name Genzyme, Framingham, MA, USA
292 rdf:type schema:Organization
293 https://www.grid.ac/institutes/grid.417993.1 schema:alternateName MSD (United States)
294 schema:name Canji, Inc., San Diego, CA, USA
295 rdf:type schema:Organization
 




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


...