Identification of DR5 as a critical, NF-κB-regulated mediator of Smac-induced apoptosis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-11

AUTHORS

I Eckhardt, S Roesler, S Fulda

ABSTRACT

Smac mimetic promotes apoptosis by neutralizing inhibitor of apoptosis (IAP) proteins and is considered as a promising cancer therapeutic. Although an autocrine/paracrine tumor necrosis factor-α (TNFα) loop has been implicated in Smac mimetic-induced cell death, little is yet known about additional factors that determine sensitivity to Smac mimetic. Using genome-wide gene expression analysis, we identify death receptor 5 (DR5) as a novel key mediator of Smac mimetic-induced apoptosis. Although several cell lines that are sensitive to the Smac mimetic BV6 die in a TNFα-dependent manner, A172 glioblastoma cells undergo BV6-induced apoptosis largely independently of TNFα/TNFR1, as the TNFα-blocking antibody Enbrel or TNFR1 knockdown provide little protection. Yet, BV6-stimulated nuclear factor-κB (NF-κB) activation is critically required for apoptosis, as inhibition of NF-κB by overexpression of dominant-negative IκBα superrepressor (IκBα-SR) blocks BV6-induced apoptosis. Unbiased genome-wide gene expression studies in IκBα-SR-overexpressing cells versus vector control cells reveal that BV6 increases DR5 expression in a NF-κB-dependent manner. Importantly, this BV6-stimulated upregulation of DR5 is critically required for apoptosis, as transient or stable knockdown of DR5 significantly inhibits BV6-triggered apoptosis. In addition, DR5 silencing attenuates formation of a RIP1/FADD/caspase-8 cytosolic cell death complex and activation of caspase-8, -3 and -9. By identifying DR5 as a critical mediator of Smac mimetic-induced apoptosis, our findings provide novel insights into the determinants that control susceptibility of cancer cells to Smac mimetic. More... »

PAGES

e936

References to SciGraph publications

  • 2008-12. Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-κB signaling in NATURE IMMUNOLOGY
  • 2011-08. Crosstalk in NF-κB signaling pathways in NATURE IMMUNOLOGY
  • 2001-04. Regulation of death receptor expression and TRAIL/Apo2L-induced apoptosis by NF-κB in NATURE CELL BIOLOGY
  • 2012-03. Identification of a novel pro-apoptotic role of NF-κB in the regulation of TRAIL- and CD95-mediated apoptosis of glioblastoma cells in ONCOGENE
  • 2009-12. A Smac-mimetic sensitizes prostate cancer cells to TRAIL-induced apoptosis via modulating both IAPs and NF-kappaB in BMC CANCER
  • 2013-02. Smac mimetic sensitizes glioblastoma cells to Temozolomide-induced apoptosis in a RIP1- and NF-κB-dependent manner in ONCOGENE
  • 2013-01. Smac mimetic Birinapant induces apoptosis and enhances TRAIL potency in inflammatory breast cancer cells in an IAP-dependent and TNF-α-independent mechanism in BREAST CANCER RESEARCH AND TREATMENT
  • 2008-12. Noncanonical NF-κB activation requires coordinated assembly of a regulatory complex of the adaptors cIAP1, cIAP2, TRAF2 and TRAF3 and the kinase NIK in NATURE IMMUNOLOGY
  • 2012-02. Targeting IAP proteins for therapeutic intervention in cancer in NATURE REVIEWS DRUG DISCOVERY
  • 2012-08. Impairment of lysosomal integrity by B10, a glycosylated derivative of betulinic acid, leads to lysosomal cell death and converts autophagy into a detrimental process in CELL DEATH & DIFFERENTIATION
  • 2007-01. Regulation of TRAIL-induced apoptosis by XIAP in pancreatic carcinoma cells in ONCOGENE
  • 2013-07. RIP1 is required for IAP inhibitor-mediated sensitization for TRAIL-induced apoptosis via a RIP1/FADD/caspase-8 cell death complex in ONCOGENE
  • 2012-02. The diverse and complex roles of NF-κB subunits in cancer in NATURE REVIEWS CANCER
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/cddis.2013.457

    DOI

    http://dx.doi.org/10.1038/cddis.2013.457

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1017272218

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/24287697


    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": "Apoptosis", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Blotting, Western", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Line", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Survival", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Immunoprecipitation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Models, Biological", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "NF-kappa B", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Real-Time Polymerase Chain Reaction", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Receptors, TNF-Related Apoptosis-Inducing Ligand", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Goethe University Frankfurt", 
              "id": "https://www.grid.ac/institutes/grid.7839.5", 
              "name": [
                "Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Komturstr. 3a, 60528 Frankfurt, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Eckhardt", 
            "givenName": "I", 
            "id": "sg:person.01017251224.26", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01017251224.26"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Goethe University Frankfurt", 
              "id": "https://www.grid.ac/institutes/grid.7839.5", 
              "name": [
                "Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Komturstr. 3a, 60528 Frankfurt, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Roesler", 
            "givenName": "S", 
            "id": "sg:person.0613234032.20", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0613234032.20"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Goethe University Frankfurt", 
              "id": "https://www.grid.ac/institutes/grid.7839.5", 
              "name": [
                "Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Komturstr. 3a, 60528 Frankfurt, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Fulda", 
            "givenName": "S", 
            "id": "sg:person.01331656400.85", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01331656400.85"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/sj.onc.1209776", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001145043", 
              "https://doi.org/10.1038/sj.onc.1209776"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1209776", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001145043", 
              "https://doi.org/10.1038/sj.onc.1209776"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrc3204", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002711966", 
              "https://doi.org/10.1038/nrc3204"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/1535-7163.mct-09-0068", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004086612"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1593/neo.11460", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005423117"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1038/sj.embor.7400795", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006661587"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ni.2065", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006965315", 
              "https://doi.org/10.1038/ni.2065"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.ccr.2007.08.029", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1008093277"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.4049/jimmunol.180.12.8030", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009151172"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/1078-0432.ccr-09-1125", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009429633"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/0008-5472.can-11-2428", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009528338"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/j.1582-4934.2009.00888.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015845763"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/j.1582-4934.2009.00888.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015845763"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/cdd.2012.10", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016341290", 
              "https://doi.org/10.1038/cdd.2012.10"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ni.1678", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1017708694", 
              "https://doi.org/10.1038/ni.1678"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/j.1582-4934.2007.00150.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021093109"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/j.1582-4934.2007.00150.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021093109"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/1471-2407-9-392", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021896313", 
              "https://doi.org/10.1186/1471-2407-9-392"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.c800128200", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024459927"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1128/mcb.25.13.5404-5416.2005", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1025198786"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.canlet.2012.10.014", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1025723370"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrd3627", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1025792112", 
              "https://doi.org/10.1038/nrd3627"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.molcel.2008.05.014", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1027166093"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cytogfr.2008.04.001", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1027726984"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cell.2008.03.036", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1031273134"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cell.2007.10.037", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032826025"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/onc.2011.333", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1035530336", 
              "https://doi.org/10.1038/onc.2011.333"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cell.2007.10.030", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036164945"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10549-012-2352-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036863515", 
              "https://doi.org/10.1007/s10549-012-2352-6"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/35070096", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037174142", 
              "https://doi.org/10.1038/35070096"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/35070096", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037174142", 
              "https://doi.org/10.1038/35070096"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/ijc.24064", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042639867"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/onc.2012.108", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050959459", 
              "https://doi.org/10.1038/onc.2012.108"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/onc.2012.337", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053056645", 
              "https://doi.org/10.1038/onc.2012.337"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/1535-7163.mct-11-0218", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053405385"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ni.1676", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053487240", 
              "https://doi.org/10.1038/ni.1676"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1083167141", 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2013-11", 
        "datePublishedReg": "2013-11-01", 
        "description": "Smac mimetic promotes apoptosis by neutralizing inhibitor of apoptosis (IAP) proteins and is considered as a promising cancer therapeutic. Although an autocrine/paracrine tumor necrosis factor-\u03b1 (TNF\u03b1) loop has been implicated in Smac mimetic-induced cell death, little is yet known about additional factors that determine sensitivity to Smac mimetic. Using genome-wide gene expression analysis, we identify death receptor 5 (DR5) as a novel key mediator of Smac mimetic-induced apoptosis. Although several cell lines that are sensitive to the Smac mimetic BV6 die in a TNF\u03b1-dependent manner, A172 glioblastoma cells undergo BV6-induced apoptosis largely independently of TNF\u03b1/TNFR1, as the TNF\u03b1-blocking antibody Enbrel or TNFR1 knockdown provide little protection. Yet, BV6-stimulated nuclear factor-\u03baB (NF-\u03baB) activation is critically required for apoptosis, as inhibition of NF-\u03baB by overexpression of dominant-negative I\u03baB\u03b1 superrepressor (I\u03baB\u03b1-SR) blocks BV6-induced apoptosis. Unbiased genome-wide gene expression studies in I\u03baB\u03b1-SR-overexpressing cells versus vector control cells reveal that BV6 increases DR5 expression in a NF-\u03baB-dependent manner. Importantly, this BV6-stimulated upregulation of DR5 is critically required for apoptosis, as transient or stable knockdown of DR5 significantly inhibits BV6-triggered apoptosis. In addition, DR5 silencing attenuates formation of a RIP1/FADD/caspase-8 cytosolic cell death complex and activation of caspase-8, -3 and -9. By identifying DR5 as a critical mediator of Smac mimetic-induced apoptosis, our findings provide novel insights into the determinants that control susceptibility of cancer cells to Smac mimetic. ", 
        "genre": "research_article", 
        "id": "sg:pub.10.1038/cddis.2013.457", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": true, 
        "isPartOf": [
          {
            "id": "sg:journal.1042939", 
            "issn": [
              "2041-4889"
            ], 
            "name": "Cell Death & Disease", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "11", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "4"
          }
        ], 
        "name": "Identification of DR5 as a critical, NF-\u03baB-regulated mediator of Smac-induced apoptosis", 
        "pagination": "e936", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "524aa7c7d75da394f504b561242724d4a28c67ee1d2b80ac383894312322d4df"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "24287697"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "101524092"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/cddis.2013.457"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1017272218"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/cddis.2013.457", 
          "https://app.dimensions.ai/details/publication/pub.1017272218"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-10T17:20", 
        "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/v90/0000000001_0000000264/records_8672_00000435.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://www.nature.com/articles/cddis2013457"
      }
    ]
     

    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/cddis.2013.457'

    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/cddis.2013.457'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/cddis.2013.457'

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

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/cddis.2013.457'


     

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

    233 TRIPLES      21 PREDICATES      72 URIs      31 LITERALS      19 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/cddis.2013.457 schema:about N0bbc7bc3d4e343b38c20ed597d5bcf6e
    2 N12e5e2eb4b764ccdac21bba2c73ca2e9
    3 N55f2f8fc1eb341968f37129719f5031f
    4 N58e2ebeee8c64685a94dff372a8df91d
    5 N62aa7f2292f742ee8b3baa072db93b48
    6 N8b9ab238ff374f29b445da8e54df010f
    7 Ncc5297c6586d4605ab450d9feb4aa13a
    8 Ne228230b8f804b5da5d5c8d5375fa1a1
    9 Ne964215d886a4d17ad10e226c09c48b8
    10 Neb39ec4d28854d488eabf9561b446a32
    11 anzsrc-for:06
    12 anzsrc-for:0601
    13 schema:author N3e0a5e5dfc9f47fdba5ab494f3f41ccb
    14 schema:citation sg:pub.10.1007/s10549-012-2352-6
    15 sg:pub.10.1038/35070096
    16 sg:pub.10.1038/cdd.2012.10
    17 sg:pub.10.1038/ni.1676
    18 sg:pub.10.1038/ni.1678
    19 sg:pub.10.1038/ni.2065
    20 sg:pub.10.1038/nrc3204
    21 sg:pub.10.1038/nrd3627
    22 sg:pub.10.1038/onc.2011.333
    23 sg:pub.10.1038/onc.2012.108
    24 sg:pub.10.1038/onc.2012.337
    25 sg:pub.10.1038/sj.onc.1209776
    26 sg:pub.10.1186/1471-2407-9-392
    27 https://app.dimensions.ai/details/publication/pub.1083167141
    28 https://doi.org/10.1002/ijc.24064
    29 https://doi.org/10.1016/j.canlet.2012.10.014
    30 https://doi.org/10.1016/j.ccr.2007.08.029
    31 https://doi.org/10.1016/j.cell.2007.10.030
    32 https://doi.org/10.1016/j.cell.2007.10.037
    33 https://doi.org/10.1016/j.cell.2008.03.036
    34 https://doi.org/10.1016/j.cytogfr.2008.04.001
    35 https://doi.org/10.1016/j.molcel.2008.05.014
    36 https://doi.org/10.1038/sj.embor.7400795
    37 https://doi.org/10.1074/jbc.c800128200
    38 https://doi.org/10.1111/j.1582-4934.2007.00150.x
    39 https://doi.org/10.1111/j.1582-4934.2009.00888.x
    40 https://doi.org/10.1128/mcb.25.13.5404-5416.2005
    41 https://doi.org/10.1158/0008-5472.can-11-2428
    42 https://doi.org/10.1158/1078-0432.ccr-09-1125
    43 https://doi.org/10.1158/1535-7163.mct-09-0068
    44 https://doi.org/10.1158/1535-7163.mct-11-0218
    45 https://doi.org/10.1593/neo.11460
    46 https://doi.org/10.4049/jimmunol.180.12.8030
    47 schema:datePublished 2013-11
    48 schema:datePublishedReg 2013-11-01
    49 schema:description Smac mimetic promotes apoptosis by neutralizing inhibitor of apoptosis (IAP) proteins and is considered as a promising cancer therapeutic. Although an autocrine/paracrine tumor necrosis factor-α (TNFα) loop has been implicated in Smac mimetic-induced cell death, little is yet known about additional factors that determine sensitivity to Smac mimetic. Using genome-wide gene expression analysis, we identify death receptor 5 (DR5) as a novel key mediator of Smac mimetic-induced apoptosis. Although several cell lines that are sensitive to the Smac mimetic BV6 die in a TNFα-dependent manner, A172 glioblastoma cells undergo BV6-induced apoptosis largely independently of TNFα/TNFR1, as the TNFα-blocking antibody Enbrel or TNFR1 knockdown provide little protection. Yet, BV6-stimulated nuclear factor-κB (NF-κB) activation is critically required for apoptosis, as inhibition of NF-κB by overexpression of dominant-negative IκBα superrepressor (IκBα-SR) blocks BV6-induced apoptosis. Unbiased genome-wide gene expression studies in IκBα-SR-overexpressing cells versus vector control cells reveal that BV6 increases DR5 expression in a NF-κB-dependent manner. Importantly, this BV6-stimulated upregulation of DR5 is critically required for apoptosis, as transient or stable knockdown of DR5 significantly inhibits BV6-triggered apoptosis. In addition, DR5 silencing attenuates formation of a RIP1/FADD/caspase-8 cytosolic cell death complex and activation of caspase-8, -3 and -9. By identifying DR5 as a critical mediator of Smac mimetic-induced apoptosis, our findings provide novel insights into the determinants that control susceptibility of cancer cells to Smac mimetic.
    50 schema:genre research_article
    51 schema:inLanguage en
    52 schema:isAccessibleForFree true
    53 schema:isPartOf N63d308b15f5946cd85c709b6b0ac3f47
    54 Nc2a13a55a17c4f6fad5789ae4e3fe18f
    55 sg:journal.1042939
    56 schema:name Identification of DR5 as a critical, NF-κB-regulated mediator of Smac-induced apoptosis
    57 schema:pagination e936
    58 schema:productId N27a0f358aaea47839f70dafebea6e60c
    59 N422e14a71a5c41cf9bdd86dab4b28b16
    60 N4885d34d2a1e46d8ad77222c48d3a3e1
    61 N6e9d167ec07e40079a0b6102e8c49bdf
    62 N7c0f81a8a5294cd0bc44e0cea6a31047
    63 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017272218
    64 https://doi.org/10.1038/cddis.2013.457
    65 schema:sdDatePublished 2019-04-10T17:20
    66 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    67 schema:sdPublisher N14f47f3b73dc496d8d0a47fb45ebceea
    68 schema:url https://www.nature.com/articles/cddis2013457
    69 sgo:license sg:explorer/license/
    70 sgo:sdDataset articles
    71 rdf:type schema:ScholarlyArticle
    72 N0bbc7bc3d4e343b38c20ed597d5bcf6e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    73 schema:name Cell Line
    74 rdf:type schema:DefinedTerm
    75 N12e5e2eb4b764ccdac21bba2c73ca2e9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    76 schema:name Humans
    77 rdf:type schema:DefinedTerm
    78 N14f47f3b73dc496d8d0a47fb45ebceea schema:name Springer Nature - SN SciGraph project
    79 rdf:type schema:Organization
    80 N21ed6e747910443fb6777841189cac28 rdf:first sg:person.0613234032.20
    81 rdf:rest N494fb7b465334a72a98a11e5cc7bd8a9
    82 N27a0f358aaea47839f70dafebea6e60c schema:name doi
    83 schema:value 10.1038/cddis.2013.457
    84 rdf:type schema:PropertyValue
    85 N3e0a5e5dfc9f47fdba5ab494f3f41ccb rdf:first sg:person.01017251224.26
    86 rdf:rest N21ed6e747910443fb6777841189cac28
    87 N422e14a71a5c41cf9bdd86dab4b28b16 schema:name readcube_id
    88 schema:value 524aa7c7d75da394f504b561242724d4a28c67ee1d2b80ac383894312322d4df
    89 rdf:type schema:PropertyValue
    90 N4885d34d2a1e46d8ad77222c48d3a3e1 schema:name dimensions_id
    91 schema:value pub.1017272218
    92 rdf:type schema:PropertyValue
    93 N494fb7b465334a72a98a11e5cc7bd8a9 rdf:first sg:person.01331656400.85
    94 rdf:rest rdf:nil
    95 N55f2f8fc1eb341968f37129719f5031f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    96 schema:name Blotting, Western
    97 rdf:type schema:DefinedTerm
    98 N58e2ebeee8c64685a94dff372a8df91d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    99 schema:name Apoptosis
    100 rdf:type schema:DefinedTerm
    101 N62aa7f2292f742ee8b3baa072db93b48 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    102 schema:name Real-Time Polymerase Chain Reaction
    103 rdf:type schema:DefinedTerm
    104 N63d308b15f5946cd85c709b6b0ac3f47 schema:volumeNumber 4
    105 rdf:type schema:PublicationVolume
    106 N6e9d167ec07e40079a0b6102e8c49bdf schema:name pubmed_id
    107 schema:value 24287697
    108 rdf:type schema:PropertyValue
    109 N7c0f81a8a5294cd0bc44e0cea6a31047 schema:name nlm_unique_id
    110 schema:value 101524092
    111 rdf:type schema:PropertyValue
    112 N8b9ab238ff374f29b445da8e54df010f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    113 schema:name NF-kappa B
    114 rdf:type schema:DefinedTerm
    115 Nc2a13a55a17c4f6fad5789ae4e3fe18f schema:issueNumber 11
    116 rdf:type schema:PublicationIssue
    117 Ncc5297c6586d4605ab450d9feb4aa13a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    118 schema:name Cell Survival
    119 rdf:type schema:DefinedTerm
    120 Ne228230b8f804b5da5d5c8d5375fa1a1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    121 schema:name Immunoprecipitation
    122 rdf:type schema:DefinedTerm
    123 Ne964215d886a4d17ad10e226c09c48b8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    124 schema:name Models, Biological
    125 rdf:type schema:DefinedTerm
    126 Neb39ec4d28854d488eabf9561b446a32 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    127 schema:name Receptors, TNF-Related Apoptosis-Inducing Ligand
    128 rdf:type schema:DefinedTerm
    129 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
    130 schema:name Biological Sciences
    131 rdf:type schema:DefinedTerm
    132 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
    133 schema:name Biochemistry and Cell Biology
    134 rdf:type schema:DefinedTerm
    135 sg:journal.1042939 schema:issn 2041-4889
    136 schema:name Cell Death & Disease
    137 rdf:type schema:Periodical
    138 sg:person.01017251224.26 schema:affiliation https://www.grid.ac/institutes/grid.7839.5
    139 schema:familyName Eckhardt
    140 schema:givenName I
    141 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01017251224.26
    142 rdf:type schema:Person
    143 sg:person.01331656400.85 schema:affiliation https://www.grid.ac/institutes/grid.7839.5
    144 schema:familyName Fulda
    145 schema:givenName S
    146 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01331656400.85
    147 rdf:type schema:Person
    148 sg:person.0613234032.20 schema:affiliation https://www.grid.ac/institutes/grid.7839.5
    149 schema:familyName Roesler
    150 schema:givenName S
    151 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0613234032.20
    152 rdf:type schema:Person
    153 sg:pub.10.1007/s10549-012-2352-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036863515
    154 https://doi.org/10.1007/s10549-012-2352-6
    155 rdf:type schema:CreativeWork
    156 sg:pub.10.1038/35070096 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037174142
    157 https://doi.org/10.1038/35070096
    158 rdf:type schema:CreativeWork
    159 sg:pub.10.1038/cdd.2012.10 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016341290
    160 https://doi.org/10.1038/cdd.2012.10
    161 rdf:type schema:CreativeWork
    162 sg:pub.10.1038/ni.1676 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053487240
    163 https://doi.org/10.1038/ni.1676
    164 rdf:type schema:CreativeWork
    165 sg:pub.10.1038/ni.1678 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017708694
    166 https://doi.org/10.1038/ni.1678
    167 rdf:type schema:CreativeWork
    168 sg:pub.10.1038/ni.2065 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006965315
    169 https://doi.org/10.1038/ni.2065
    170 rdf:type schema:CreativeWork
    171 sg:pub.10.1038/nrc3204 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002711966
    172 https://doi.org/10.1038/nrc3204
    173 rdf:type schema:CreativeWork
    174 sg:pub.10.1038/nrd3627 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025792112
    175 https://doi.org/10.1038/nrd3627
    176 rdf:type schema:CreativeWork
    177 sg:pub.10.1038/onc.2011.333 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035530336
    178 https://doi.org/10.1038/onc.2011.333
    179 rdf:type schema:CreativeWork
    180 sg:pub.10.1038/onc.2012.108 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050959459
    181 https://doi.org/10.1038/onc.2012.108
    182 rdf:type schema:CreativeWork
    183 sg:pub.10.1038/onc.2012.337 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053056645
    184 https://doi.org/10.1038/onc.2012.337
    185 rdf:type schema:CreativeWork
    186 sg:pub.10.1038/sj.onc.1209776 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001145043
    187 https://doi.org/10.1038/sj.onc.1209776
    188 rdf:type schema:CreativeWork
    189 sg:pub.10.1186/1471-2407-9-392 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021896313
    190 https://doi.org/10.1186/1471-2407-9-392
    191 rdf:type schema:CreativeWork
    192 https://app.dimensions.ai/details/publication/pub.1083167141 schema:CreativeWork
    193 https://doi.org/10.1002/ijc.24064 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042639867
    194 rdf:type schema:CreativeWork
    195 https://doi.org/10.1016/j.canlet.2012.10.014 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025723370
    196 rdf:type schema:CreativeWork
    197 https://doi.org/10.1016/j.ccr.2007.08.029 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008093277
    198 rdf:type schema:CreativeWork
    199 https://doi.org/10.1016/j.cell.2007.10.030 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036164945
    200 rdf:type schema:CreativeWork
    201 https://doi.org/10.1016/j.cell.2007.10.037 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032826025
    202 rdf:type schema:CreativeWork
    203 https://doi.org/10.1016/j.cell.2008.03.036 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031273134
    204 rdf:type schema:CreativeWork
    205 https://doi.org/10.1016/j.cytogfr.2008.04.001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027726984
    206 rdf:type schema:CreativeWork
    207 https://doi.org/10.1016/j.molcel.2008.05.014 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027166093
    208 rdf:type schema:CreativeWork
    209 https://doi.org/10.1038/sj.embor.7400795 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006661587
    210 rdf:type schema:CreativeWork
    211 https://doi.org/10.1074/jbc.c800128200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024459927
    212 rdf:type schema:CreativeWork
    213 https://doi.org/10.1111/j.1582-4934.2007.00150.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1021093109
    214 rdf:type schema:CreativeWork
    215 https://doi.org/10.1111/j.1582-4934.2009.00888.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1015845763
    216 rdf:type schema:CreativeWork
    217 https://doi.org/10.1128/mcb.25.13.5404-5416.2005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025198786
    218 rdf:type schema:CreativeWork
    219 https://doi.org/10.1158/0008-5472.can-11-2428 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009528338
    220 rdf:type schema:CreativeWork
    221 https://doi.org/10.1158/1078-0432.ccr-09-1125 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009429633
    222 rdf:type schema:CreativeWork
    223 https://doi.org/10.1158/1535-7163.mct-09-0068 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004086612
    224 rdf:type schema:CreativeWork
    225 https://doi.org/10.1158/1535-7163.mct-11-0218 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053405385
    226 rdf:type schema:CreativeWork
    227 https://doi.org/10.1593/neo.11460 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005423117
    228 rdf:type schema:CreativeWork
    229 https://doi.org/10.4049/jimmunol.180.12.8030 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009151172
    230 rdf:type schema:CreativeWork
    231 https://www.grid.ac/institutes/grid.7839.5 schema:alternateName Goethe University Frankfurt
    232 schema:name Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Komturstr. 3a, 60528 Frankfurt, Germany
    233 rdf:type schema:Organization
     




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


    ...