Characterization of distinct consecutive phases in non-genotoxic p53-induced apoptosis of Ewing tumor cells and the rate-limiting role of caspase 8 View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2000-08-24

AUTHORS

H Kovar, G Jug, D Printz, S Bartl, G Schmid, J Wesierska-Gadek

ABSTRACT

To dissect the p53-dependent apoptotic pathway, events following induction of temperature sensitive (ts) p53val138 were studied in a Ewing tumor cell line. Transcriptional deregulation of p53 targets first observable after 1 h at 32°C preceded activation of caspases and the break-down of mitochondrial respiratory activity. Activation of caspases was first observed 4 h after p53 induction. Using peptide inhibitors we identified activation of caspase 8 upstream of caspases-9 and -3. Although the caspase 8 specific inhibitor z-IETD.fmk did not affect translocation of BAX to the mitochondrial membrane and cytochrome C release it almost completely blocked cleavage of the prototype caspase substrate PARP and DNA fragmentation while enforcing mitochondrial depolarization and production of reactive oxygene species (ROS). Activation of caspase 8 did not involve death-domain receptor signaling. Expression of BCL2 only partially suppressed caspase activation but blocked apoptosis. Replacement of the N-terminus of p53val138 by the related VP16 transactivation domain created a ts p53 with a tanscriptional activity indistinguishable from p53val138 until the time of caspase activation. However, the VP16–p53 fusion failed to trigger caspases and subsequent induction of the ROS producing gene pig3 paralleled by complete loss of apoptotic activity. These results indicate that p53-dependent transcriptional deregulation, triggering of the caspase cascade and the mitochondrial break-down occur in a timely ordered sequence coordinated by the genuine p53 amino terminus and suggest caspase 8 and PIG3 as key regulatory elements in this process. More... »

PAGES

4096-4107

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1203780

DOI

http://dx.doi.org/10.1038/sj.onc.1203780

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1028224318

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10962570


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/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1103", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Clinical Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Oncology and Carcinogenesis", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Apoptosis", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Blotting, Northern", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Caspase 8", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Caspase 9", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Caspase Inhibitors", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Caspases", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cysteine Proteinase Inhibitors", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cytochrome c Group", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "DNA Fragmentation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Flow Cytometry", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Herpes Simplex Virus Protein Vmw65", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "In Situ Nick-End Labeling", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Intracellular Signaling Peptides and Proteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mitochondria", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mutation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Oligopeptides", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Poly(ADP-ribose) Polymerases", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Proteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Proto-Oncogene Proteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Proto-Oncogene Proteins c-bcl-2", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Reactive Oxygen Species", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Recombinant Fusion Proteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Sarcoma, Ewing", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Transcriptional Activation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Tumor Cells, Cultured", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Tumor Suppressor Protein p53", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "bcl-2-Associated X Protein", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Children's Cancer Research Institute, St. Anna Kinderspital, Vienna, Austria", 
          "id": "http://www.grid.ac/institutes/grid.416346.2", 
          "name": [
            "Children's Cancer Research Institute, St. Anna Kinderspital, Vienna, Austria"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kovar", 
        "givenName": "H", 
        "id": "sg:person.0741362200.35", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0741362200.35"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Children's Cancer Research Institute, St. Anna Kinderspital, Vienna, Austria", 
          "id": "http://www.grid.ac/institutes/grid.416346.2", 
          "name": [
            "Children's Cancer Research Institute, St. Anna Kinderspital, Vienna, Austria"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Jug", 
        "givenName": "G", 
        "id": "sg:person.01004112075.20", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01004112075.20"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Children's Cancer Research Institute, St. Anna Kinderspital, Vienna, Austria", 
          "id": "http://www.grid.ac/institutes/grid.416346.2", 
          "name": [
            "Children's Cancer Research Institute, St. Anna Kinderspital, Vienna, Austria"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Printz", 
        "givenName": "D", 
        "id": "sg:person.01164336746.44", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01164336746.44"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Children's Cancer Research Institute, St. Anna Kinderspital, Vienna, Austria", 
          "id": "http://www.grid.ac/institutes/grid.416346.2", 
          "name": [
            "Children's Cancer Research Institute, St. Anna Kinderspital, Vienna, Austria"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Bartl", 
        "givenName": "S", 
        "id": "sg:person.01266101453.75", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01266101453.75"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Institute of Cancer Research, University of Vienna, A-1090, Vienna, Austria", 
          "id": "http://www.grid.ac/institutes/grid.10420.37", 
          "name": [
            "Institute of Cancer Research, University of Vienna, A-1090, Vienna, Austria"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Schmid", 
        "givenName": "G", 
        "id": "sg:person.01026526161.48", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01026526161.48"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Institute of Cancer Research, University of Vienna, A-1090, Vienna, Austria", 
          "id": "http://www.grid.ac/institutes/grid.10420.37", 
          "name": [
            "Institute of Cancer Research, University of Vienna, A-1090, Vienna, Austria"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wesierska-Gadek", 
        "givenName": "J", 
        "id": "sg:person.01157067663.11", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01157067663.11"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1038/sj.onc.1202533", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028529752", 
          "https://doi.org/10.1038/sj.onc.1202533"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/370220a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001574750", 
          "https://doi.org/10.1038/370220a0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1201454", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036240154", 
          "https://doi.org/10.1038/sj.onc.1201454"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1202656", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011044542", 
          "https://doi.org/10.1038/sj.onc.1202656"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1202310", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010614186", 
          "https://doi.org/10.1038/sj.onc.1202310"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1202292", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046143552", 
          "https://doi.org/10.1038/sj.onc.1202292"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ng1097-141", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040087526", 
          "https://doi.org/10.1038/ng1097-141"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/35008667", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012881410", 
          "https://doi.org/10.1038/35008667"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.cdd.4400419", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016655503", 
          "https://doi.org/10.1038/sj.cdd.4400419"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/38525", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023661637", 
          "https://doi.org/10.1038/38525"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/20959", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031691936", 
          "https://doi.org/10.1038/20959"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/377646a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046371025", 
          "https://doi.org/10.1038/377646a0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1203489", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045600742", 
          "https://doi.org/10.1038/sj.onc.1203489"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2000-08-24", 
    "datePublishedReg": "2000-08-24", 
    "description": "To dissect the p53-dependent apoptotic pathway, events following induction of temperature sensitive (ts) p53val138 were studied in a Ewing tumor cell line. Transcriptional deregulation of p53 targets first observable after 1\u2009h at 32\u00b0C preceded activation of caspases and the break-down of mitochondrial respiratory activity. Activation of caspases was first observed 4\u2009h after p53 induction. Using peptide inhibitors we identified activation of caspase 8 upstream of caspases-9 and -3. Although the caspase 8 specific inhibitor z-IETD.fmk did not affect translocation of BAX to the mitochondrial membrane and cytochrome C release it almost completely blocked cleavage of the prototype caspase substrate PARP and DNA fragmentation while enforcing mitochondrial depolarization and production of reactive oxygene species (ROS). Activation of caspase 8 did not involve death-domain receptor signaling. Expression of BCL2 only partially suppressed caspase activation but blocked apoptosis. Replacement of the N-terminus of p53val138 by the related VP16 transactivation domain created a ts p53 with a tanscriptional activity indistinguishable from p53val138 until the time of caspase activation. However, the VP16\u2013p53 fusion failed to trigger caspases and subsequent induction of the ROS producing gene pig3 paralleled by complete loss of apoptotic activity. These results indicate that p53-dependent transcriptional deregulation, triggering of the caspase cascade and the mitochondrial break-down occur in a timely ordered sequence coordinated by the genuine p53 amino terminus and suggest caspase 8 and PIG3 as key regulatory elements in this process.", 
    "genre": "article", 
    "id": "sg:pub.10.1038/sj.onc.1203780", 
    "isAccessibleForFree": false, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.6189318", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1097543", 
        "issn": [
          "0950-9232", 
          "1476-5594"
        ], 
        "name": "Oncogene", 
        "publisher": "Springer Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "36", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "19"
      }
    ], 
    "keywords": [
      "reactive oxygene species", 
      "activation of caspases", 
      "caspase-8", 
      "transcriptional deregulation", 
      "caspase activation", 
      "VP16 transactivation domain", 
      "translocation of Bax", 
      "p53-dependent apoptotic pathway", 
      "cytochrome c release", 
      "key regulatory elements", 
      "caspase substrate PARP", 
      "p53-induced apoptosis", 
      "distinct consecutive phases", 
      "rate-limiting role", 
      "mitochondrial respiratory activity", 
      "transactivation domain", 
      "Z-IETD", 
      "regulatory elements", 
      "mitochondrial membrane", 
      "caspase cascade", 
      "c release", 
      "amino terminus", 
      "p53 targets", 
      "substrate PARP", 
      "N-terminus", 
      "apoptotic pathway", 
      "mitochondrial depolarization", 
      "caspase-9", 
      "p53 induction", 
      "DNA fragmentation", 
      "receptor signaling", 
      "expression of Bcl2", 
      "caspases", 
      "tumor cell lines", 
      "apoptotic activity", 
      "peptide inhibitor", 
      "ts p53", 
      "cell lines", 
      "complete loss", 
      "subsequent induction", 
      "respiratory activity", 
      "apoptosis", 
      "activation", 
      "deregulation", 
      "induction", 
      "tumor cells", 
      "fmk", 
      "genes", 
      "terminus", 
      "signaling", 
      "species", 
      "translocation", 
      "PARP", 
      "Bax", 
      "upstream", 
      "pathway", 
      "activity", 
      "p53", 
      "cascade", 
      "BCL2", 
      "sequence", 
      "expression", 
      "membrane", 
      "cleavage", 
      "cells", 
      "inhibitors", 
      "fragmentation", 
      "domain", 
      "target", 
      "fusion", 
      "breaks", 
      "role", 
      "production", 
      "lines", 
      "characterization", 
      "depolarization", 
      "release", 
      "occurs", 
      "consecutive phases", 
      "loss", 
      "events", 
      "elements", 
      "process", 
      "replacement", 
      "results", 
      "time", 
      "phase"
    ], 
    "name": "Characterization of distinct consecutive phases in non-genotoxic p53-induced apoptosis of Ewing tumor cells and the rate-limiting role of caspase 8", 
    "pagination": "4096-4107", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1028224318"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/sj.onc.1203780"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "10962570"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/sj.onc.1203780", 
      "https://app.dimensions.ai/details/publication/pub.1028224318"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2022-10-01T06:30", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-springernature-scigraph/baseset/20221001/entities/gbq_results/article/article_319.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1038/sj.onc.1203780"
  }
]
 

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.onc.1203780'

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.onc.1203780'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/sj.onc.1203780'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/sj.onc.1203780'


 

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

356 TRIPLES      21 PREDICATES      154 URIs      132 LITERALS      35 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/sj.onc.1203780 schema:about N01f2b89f7ef748579cb3da7f2d1be66c
2 N074cdb83763a46cb937b190217a7df3d
3 N08f444de214a4c95bd8cc0c77e6522c1
4 N0a645e7ecaa241c18d4995b048da8176
5 N1e3be20a6cc5432a8718d3cb4fb798bd
6 N2c70c7dd68e94392b4936c77d0342586
7 N48a29f4fc36c42ae85f21dee1fa65e7f
8 N573abcf1e3874d499ae87f74c449786a
9 N671cae0bce24481e9691d651871d28b3
10 N6f3104702a894cde8b4011f1a0f1fc86
11 N7314f019fc9c41caaa26f7564a5ac134
12 N74d65dfb586e49e7b67bc926e6bb6f6d
13 N79ea0d2faa67482d991c2260b083faa6
14 N97d408586be24d2a89cba9ce9721606b
15 Na5a69a9ab0c14d1eab99b06afba7f39a
16 Nafe0bd731c574b5d86815c721150d604
17 Nb4f10b72264c47e8a1997ae200cd8175
18 Nbbf8c48a716844b0b0fe0ee569f5b306
19 Nbfe5e5557a5f40ce8229abe92ef9d86c
20 Nc2de0f23a37449ecb09fada11628df13
21 Nc65cd639f350433299b00697b6d658ac
22 Ncdf3882926514594938c31020144304a
23 Nd2728ffaf0ac4afda228b32cc2dc3db6
24 Nd91e256dfda94f5aae4f7bc62bd96870
25 Ne5eff26febad43a9899c7685a236cbe1
26 Ne6c02f932cdd4c30b98780d6671950cb
27 Nee4c8c6cd1324dd484851f502f56b4f4
28 Nfeec51c9044d4e15a5d8eaba53e77fd5
29 anzsrc-for:11
30 anzsrc-for:1103
31 anzsrc-for:1112
32 schema:author N4b17319e2c74447f896d6cb588419ebd
33 schema:citation sg:pub.10.1038/20959
34 sg:pub.10.1038/35008667
35 sg:pub.10.1038/370220a0
36 sg:pub.10.1038/377646a0
37 sg:pub.10.1038/38525
38 sg:pub.10.1038/ng1097-141
39 sg:pub.10.1038/sj.cdd.4400419
40 sg:pub.10.1038/sj.onc.1201454
41 sg:pub.10.1038/sj.onc.1202292
42 sg:pub.10.1038/sj.onc.1202310
43 sg:pub.10.1038/sj.onc.1202533
44 sg:pub.10.1038/sj.onc.1202656
45 sg:pub.10.1038/sj.onc.1203489
46 schema:datePublished 2000-08-24
47 schema:datePublishedReg 2000-08-24
48 schema:description To dissect the p53-dependent apoptotic pathway, events following induction of temperature sensitive (ts) p53val138 were studied in a Ewing tumor cell line. Transcriptional deregulation of p53 targets first observable after 1 h at 32°C preceded activation of caspases and the break-down of mitochondrial respiratory activity. Activation of caspases was first observed 4 h after p53 induction. Using peptide inhibitors we identified activation of caspase 8 upstream of caspases-9 and -3. Although the caspase 8 specific inhibitor z-IETD.fmk did not affect translocation of BAX to the mitochondrial membrane and cytochrome C release it almost completely blocked cleavage of the prototype caspase substrate PARP and DNA fragmentation while enforcing mitochondrial depolarization and production of reactive oxygene species (ROS). Activation of caspase 8 did not involve death-domain receptor signaling. Expression of BCL2 only partially suppressed caspase activation but blocked apoptosis. Replacement of the N-terminus of p53val138 by the related VP16 transactivation domain created a ts p53 with a tanscriptional activity indistinguishable from p53val138 until the time of caspase activation. However, the VP16–p53 fusion failed to trigger caspases and subsequent induction of the ROS producing gene pig3 paralleled by complete loss of apoptotic activity. These results indicate that p53-dependent transcriptional deregulation, triggering of the caspase cascade and the mitochondrial break-down occur in a timely ordered sequence coordinated by the genuine p53 amino terminus and suggest caspase 8 and PIG3 as key regulatory elements in this process.
49 schema:genre article
50 schema:isAccessibleForFree false
51 schema:isPartOf N12d7e9ff64e24ff99295f4e42f4bbcc1
52 Nd055e5dd6c6f4393a07dafeae69beabd
53 sg:journal.1097543
54 schema:keywords BCL2
55 Bax
56 DNA fragmentation
57 N-terminus
58 PARP
59 VP16 transactivation domain
60 Z-IETD
61 activation
62 activation of caspases
63 activity
64 amino terminus
65 apoptosis
66 apoptotic activity
67 apoptotic pathway
68 breaks
69 c release
70 cascade
71 caspase activation
72 caspase cascade
73 caspase substrate PARP
74 caspase-8
75 caspase-9
76 caspases
77 cell lines
78 cells
79 characterization
80 cleavage
81 complete loss
82 consecutive phases
83 cytochrome c release
84 depolarization
85 deregulation
86 distinct consecutive phases
87 domain
88 elements
89 events
90 expression
91 expression of Bcl2
92 fmk
93 fragmentation
94 fusion
95 genes
96 induction
97 inhibitors
98 key regulatory elements
99 lines
100 loss
101 membrane
102 mitochondrial depolarization
103 mitochondrial membrane
104 mitochondrial respiratory activity
105 occurs
106 p53
107 p53 induction
108 p53 targets
109 p53-dependent apoptotic pathway
110 p53-induced apoptosis
111 pathway
112 peptide inhibitor
113 phase
114 process
115 production
116 rate-limiting role
117 reactive oxygene species
118 receptor signaling
119 regulatory elements
120 release
121 replacement
122 respiratory activity
123 results
124 role
125 sequence
126 signaling
127 species
128 subsequent induction
129 substrate PARP
130 target
131 terminus
132 time
133 transactivation domain
134 transcriptional deregulation
135 translocation
136 translocation of Bax
137 ts p53
138 tumor cell lines
139 tumor cells
140 upstream
141 schema:name Characterization of distinct consecutive phases in non-genotoxic p53-induced apoptosis of Ewing tumor cells and the rate-limiting role of caspase 8
142 schema:pagination 4096-4107
143 schema:productId N4aa5db77b6e4443898446bed11a891bf
144 N6ce70fcff29649d7bd48b4de8028280e
145 Nf7e0e8968a7947b08cdb26b0d5c112e1
146 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028224318
147 https://doi.org/10.1038/sj.onc.1203780
148 schema:sdDatePublished 2022-10-01T06:30
149 schema:sdLicense https://scigraph.springernature.com/explorer/license/
150 schema:sdPublisher N7c3e1261b57c494595efc6471c14f4b0
151 schema:url https://doi.org/10.1038/sj.onc.1203780
152 sgo:license sg:explorer/license/
153 sgo:sdDataset articles
154 rdf:type schema:ScholarlyArticle
155 N00ab56a5965a461c9cc787b27712cb17 rdf:first sg:person.01157067663.11
156 rdf:rest rdf:nil
157 N01f2b89f7ef748579cb3da7f2d1be66c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
158 schema:name Caspase 8
159 rdf:type schema:DefinedTerm
160 N074cdb83763a46cb937b190217a7df3d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
161 schema:name Blotting, Northern
162 rdf:type schema:DefinedTerm
163 N08f444de214a4c95bd8cc0c77e6522c1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
164 schema:name Cysteine Proteinase Inhibitors
165 rdf:type schema:DefinedTerm
166 N0a645e7ecaa241c18d4995b048da8176 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
167 schema:name Transcriptional Activation
168 rdf:type schema:DefinedTerm
169 N12d7e9ff64e24ff99295f4e42f4bbcc1 schema:volumeNumber 19
170 rdf:type schema:PublicationVolume
171 N1456d5de81644b21b9af85f1daa4ae38 rdf:first sg:person.01266101453.75
172 rdf:rest N6e24afabde0c4996b40838fcdcb7c474
173 N1e3be20a6cc5432a8718d3cb4fb798bd schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
174 schema:name In Situ Nick-End Labeling
175 rdf:type schema:DefinedTerm
176 N2c70c7dd68e94392b4936c77d0342586 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
177 schema:name Flow Cytometry
178 rdf:type schema:DefinedTerm
179 N48a29f4fc36c42ae85f21dee1fa65e7f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
180 schema:name Mutation
181 rdf:type schema:DefinedTerm
182 N4aa5db77b6e4443898446bed11a891bf schema:name doi
183 schema:value 10.1038/sj.onc.1203780
184 rdf:type schema:PropertyValue
185 N4b17319e2c74447f896d6cb588419ebd rdf:first sg:person.0741362200.35
186 rdf:rest N935aef29fc854978987cfd313de7a048
187 N573abcf1e3874d499ae87f74c449786a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
188 schema:name Reactive Oxygen Species
189 rdf:type schema:DefinedTerm
190 N671cae0bce24481e9691d651871d28b3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
191 schema:name Caspase 9
192 rdf:type schema:DefinedTerm
193 N6ce70fcff29649d7bd48b4de8028280e schema:name dimensions_id
194 schema:value pub.1028224318
195 rdf:type schema:PropertyValue
196 N6e24afabde0c4996b40838fcdcb7c474 rdf:first sg:person.01026526161.48
197 rdf:rest N00ab56a5965a461c9cc787b27712cb17
198 N6f3104702a894cde8b4011f1a0f1fc86 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
199 schema:name Sarcoma, Ewing
200 rdf:type schema:DefinedTerm
201 N7314f019fc9c41caaa26f7564a5ac134 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
202 schema:name Proto-Oncogene Proteins
203 rdf:type schema:DefinedTerm
204 N74d65dfb586e49e7b67bc926e6bb6f6d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
205 schema:name Herpes Simplex Virus Protein Vmw65
206 rdf:type schema:DefinedTerm
207 N79ea0d2faa67482d991c2260b083faa6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
208 schema:name Humans
209 rdf:type schema:DefinedTerm
210 N7c3e1261b57c494595efc6471c14f4b0 schema:name Springer Nature - SN SciGraph project
211 rdf:type schema:Organization
212 N935aef29fc854978987cfd313de7a048 rdf:first sg:person.01004112075.20
213 rdf:rest Nae16bf33f8b24c838e8e28e0af9bc1d7
214 N97d408586be24d2a89cba9ce9721606b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
215 schema:name Recombinant Fusion Proteins
216 rdf:type schema:DefinedTerm
217 Na5a69a9ab0c14d1eab99b06afba7f39a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
218 schema:name Caspase Inhibitors
219 rdf:type schema:DefinedTerm
220 Nae16bf33f8b24c838e8e28e0af9bc1d7 rdf:first sg:person.01164336746.44
221 rdf:rest N1456d5de81644b21b9af85f1daa4ae38
222 Nafe0bd731c574b5d86815c721150d604 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
223 schema:name bcl-2-Associated X Protein
224 rdf:type schema:DefinedTerm
225 Nb4f10b72264c47e8a1997ae200cd8175 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
226 schema:name Intracellular Signaling Peptides and Proteins
227 rdf:type schema:DefinedTerm
228 Nbbf8c48a716844b0b0fe0ee569f5b306 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
229 schema:name Proto-Oncogene Proteins c-bcl-2
230 rdf:type schema:DefinedTerm
231 Nbfe5e5557a5f40ce8229abe92ef9d86c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
232 schema:name Mitochondria
233 rdf:type schema:DefinedTerm
234 Nc2de0f23a37449ecb09fada11628df13 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
235 schema:name DNA Fragmentation
236 rdf:type schema:DefinedTerm
237 Nc65cd639f350433299b00697b6d658ac schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
238 schema:name Tumor Cells, Cultured
239 rdf:type schema:DefinedTerm
240 Ncdf3882926514594938c31020144304a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
241 schema:name Poly(ADP-ribose) Polymerases
242 rdf:type schema:DefinedTerm
243 Nd055e5dd6c6f4393a07dafeae69beabd schema:issueNumber 36
244 rdf:type schema:PublicationIssue
245 Nd2728ffaf0ac4afda228b32cc2dc3db6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
246 schema:name Apoptosis
247 rdf:type schema:DefinedTerm
248 Nd91e256dfda94f5aae4f7bc62bd96870 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
249 schema:name Cytochrome c Group
250 rdf:type schema:DefinedTerm
251 Ne5eff26febad43a9899c7685a236cbe1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
252 schema:name Oligopeptides
253 rdf:type schema:DefinedTerm
254 Ne6c02f932cdd4c30b98780d6671950cb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
255 schema:name Caspases
256 rdf:type schema:DefinedTerm
257 Nee4c8c6cd1324dd484851f502f56b4f4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
258 schema:name Tumor Suppressor Protein p53
259 rdf:type schema:DefinedTerm
260 Nf7e0e8968a7947b08cdb26b0d5c112e1 schema:name pubmed_id
261 schema:value 10962570
262 rdf:type schema:PropertyValue
263 Nfeec51c9044d4e15a5d8eaba53e77fd5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
264 schema:name Proteins
265 rdf:type schema:DefinedTerm
266 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
267 schema:name Medical and Health Sciences
268 rdf:type schema:DefinedTerm
269 anzsrc-for:1103 schema:inDefinedTermSet anzsrc-for:
270 schema:name Clinical Sciences
271 rdf:type schema:DefinedTerm
272 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
273 schema:name Oncology and Carcinogenesis
274 rdf:type schema:DefinedTerm
275 sg:grant.6189318 http://pending.schema.org/fundedItem sg:pub.10.1038/sj.onc.1203780
276 rdf:type schema:MonetaryGrant
277 sg:journal.1097543 schema:issn 0950-9232
278 1476-5594
279 schema:name Oncogene
280 schema:publisher Springer Nature
281 rdf:type schema:Periodical
282 sg:person.01004112075.20 schema:affiliation grid-institutes:grid.416346.2
283 schema:familyName Jug
284 schema:givenName G
285 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01004112075.20
286 rdf:type schema:Person
287 sg:person.01026526161.48 schema:affiliation grid-institutes:grid.10420.37
288 schema:familyName Schmid
289 schema:givenName G
290 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01026526161.48
291 rdf:type schema:Person
292 sg:person.01157067663.11 schema:affiliation grid-institutes:grid.10420.37
293 schema:familyName Wesierska-Gadek
294 schema:givenName J
295 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01157067663.11
296 rdf:type schema:Person
297 sg:person.01164336746.44 schema:affiliation grid-institutes:grid.416346.2
298 schema:familyName Printz
299 schema:givenName D
300 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01164336746.44
301 rdf:type schema:Person
302 sg:person.01266101453.75 schema:affiliation grid-institutes:grid.416346.2
303 schema:familyName Bartl
304 schema:givenName S
305 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01266101453.75
306 rdf:type schema:Person
307 sg:person.0741362200.35 schema:affiliation grid-institutes:grid.416346.2
308 schema:familyName Kovar
309 schema:givenName H
310 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0741362200.35
311 rdf:type schema:Person
312 sg:pub.10.1038/20959 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031691936
313 https://doi.org/10.1038/20959
314 rdf:type schema:CreativeWork
315 sg:pub.10.1038/35008667 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012881410
316 https://doi.org/10.1038/35008667
317 rdf:type schema:CreativeWork
318 sg:pub.10.1038/370220a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001574750
319 https://doi.org/10.1038/370220a0
320 rdf:type schema:CreativeWork
321 sg:pub.10.1038/377646a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046371025
322 https://doi.org/10.1038/377646a0
323 rdf:type schema:CreativeWork
324 sg:pub.10.1038/38525 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023661637
325 https://doi.org/10.1038/38525
326 rdf:type schema:CreativeWork
327 sg:pub.10.1038/ng1097-141 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040087526
328 https://doi.org/10.1038/ng1097-141
329 rdf:type schema:CreativeWork
330 sg:pub.10.1038/sj.cdd.4400419 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016655503
331 https://doi.org/10.1038/sj.cdd.4400419
332 rdf:type schema:CreativeWork
333 sg:pub.10.1038/sj.onc.1201454 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036240154
334 https://doi.org/10.1038/sj.onc.1201454
335 rdf:type schema:CreativeWork
336 sg:pub.10.1038/sj.onc.1202292 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046143552
337 https://doi.org/10.1038/sj.onc.1202292
338 rdf:type schema:CreativeWork
339 sg:pub.10.1038/sj.onc.1202310 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010614186
340 https://doi.org/10.1038/sj.onc.1202310
341 rdf:type schema:CreativeWork
342 sg:pub.10.1038/sj.onc.1202533 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028529752
343 https://doi.org/10.1038/sj.onc.1202533
344 rdf:type schema:CreativeWork
345 sg:pub.10.1038/sj.onc.1202656 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011044542
346 https://doi.org/10.1038/sj.onc.1202656
347 rdf:type schema:CreativeWork
348 sg:pub.10.1038/sj.onc.1203489 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045600742
349 https://doi.org/10.1038/sj.onc.1203489
350 rdf:type schema:CreativeWork
351 grid-institutes:grid.10420.37 schema:alternateName Institute of Cancer Research, University of Vienna, A-1090, Vienna, Austria
352 schema:name Institute of Cancer Research, University of Vienna, A-1090, Vienna, Austria
353 rdf:type schema:Organization
354 grid-institutes:grid.416346.2 schema:alternateName Children's Cancer Research Institute, St. Anna Kinderspital, Vienna, Austria
355 schema:name Children's Cancer Research Institute, St. Anna Kinderspital, Vienna, Austria
356 rdf:type schema:Organization
 




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


...