Ets-1 mediates upregulation of Mcl-1 downstream of XBP-1 in human melanoma cells upon ER stress View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-03-21

AUTHORS

L Dong, C C Jiang, R F Thorne, A Croft, F Yang, H Liu, C E de Bock, P Hersey, X D Zhang

ABSTRACT

Past studies have shown that upregulation of the anti-apoptotic Bcl-2 family protein Mcl-1 is a major adaptive mechanism of melanoma cells to endoplasmic reticulum (ER) stress, and has an important role in resistance of the cells to apoptosis. In this study, we show that the increase in transcription of Mcl-1 in melanoma cells triggered by pharmacological ER stress inducers is mediated by the transcription factor Ets-1. By incremental deletion analysis of the Mcl-1 promoter, we identified a DNA fragment containing an Ets-1 binding site that is transcriptionally responsive to ER stress. Mutations in the Ets-1 binding site or knockdown of Ets-1 inhibited the increase in Mcl-1, indicating that Ets-1 has a critical role in transcriptional upregulation of Mcl-1. Similar to Mcl-1, Ets-1 was transcriptionally upregulated by ER stress. This was mediated by the IRE1α/XBP-1 branch of the unfolded protein response, as upregulation of Ets-1 was inhibited in melanoma cell lines deficient in IRE1α or XBP-1 established by short hairpin RNA knockdown. Activation of the PI3k/Akt pathway downstream of XBP-1 was also involved, in that inhibition of the pathway blocked upregulation of Ets-1. Inhibition of Ets-1 enhanced ER stress-induced apoptosis in melanoma cell lines and in fresh melanoma isolates, recapitulating the effect of inhibition of Mcl-1. These results reveal a key mechanism by which Mcl-1 is transcriptionally upregulated in melanoma cells by ER stress, and identify Ets-1 as a potential target for inhibition to sensitize melanoma cells to apoptosis. More... »

PAGES

3716-3726

References to SciGraph publications

  • 2010-03-19. Cystatin B inhibition of TRAIL-induced apoptosis is associated with the protection of FLIPL from degradation by the E3 ligase itch in human melanoma cells in CELL DEATH & DIFFERENTIATION
  • 2004-01. The Ets-1 transcription factor is involved in the development and invasion of malignant melanoma in CELLULAR AND MOLECULAR LIFE SCIENCES
  • 2009-12-20. Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival in NATURE
  • 2002-12-04. Expression of the transcription factor Ets-1 is an independent prognostic marker for relapse-free survival in breast cancer in ONCOGENE
  • 2002-09-01. The Bcl2 family: regulators of the cellular life-or-death switch in NATURE REVIEWS CANCER
  • 2000-04. Functional analysis of the human MCL-1 gene in CELLULAR AND MOLECULAR LIFE SCIENCES
  • 2009-12-14. 2-Deoxy-D-glucose enhances TRAIL-induced apoptosis in human melanoma cells through XBP-1-mediated up-regulation of TRAIL-R2 in MOLECULAR CANCER
  • 2003-08-20. The Biology of the Ets1 Proto-Oncogene in MOLECULAR CANCER
  • 2007-03-26. Mcl-1, Bcl-XL and Stat3 expression are associated with progression of melanoma whereas Bcl-2, AP-2 and MITF levels decrease during progression of melanoma in MODERN PATHOLOGY
  • 2000-02-10. EAP1/Daxx interacts with ETS1 and represses transcriptional activation of ETS1 target genes in ONCOGENE
  • 2004-06-18. Ets-1 transcription factor is widely expressed in benign and malignant melanocytes and its expression has no significant association with prognosis in MODERN PATHOLOGY
  • 2003-05-19. Apoptosis and melanoma chemoresistance in ONCOGENE
  • 1995-10. Increased T-cell apoptosis and terminal B-cell differentiation induced by inactivation of the Ets-1 proto-oncogene in NATURE
  • 2009-10-16. Lactate dehydrogenase 5 expression in melanoma increases with disease progression and is associated with expression of Bcl-XL and Mcl-1, but not Bcl-2 proteins in MODERN PATHOLOGY
  • 2010-09-02. Apoptosis of human melanoma cells induced by inhibition of B-RAFV600E involves preferential splicing of bimS in CELL DEATH & DISEASE
  • 2008-01-21. The Wilms' tumour suppressor WT1 is involved in endothelial cell proliferation and migration: expression in tumour vessels in vivo in ONCOGENE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/onc.2011.87

    DOI

    http://dx.doi.org/10.1038/onc.2011.87

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1039031247

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/21423203


    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": "Base Sequence", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Blotting, Western", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Line, Tumor", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Chromatin Immunoprecipitation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "DNA Primers", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "DNA-Binding Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Electrophoretic Mobility Shift Assay", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Endoplasmic Reticulum", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Melanoma", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Myeloid Cell Leukemia Sequence 1 Protein", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Polymerase Chain Reaction", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Promoter Regions, Genetic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Proto-Oncogene Protein c-ets-1", 
            "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": "Regulatory Factor X Transcription Factors", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Transcription Factors", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Transcription, Genetic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Up-Regulation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "X-Box Binding Protein 1", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Immunology and Oncology Unit, Calvary Mater Newcastle Hospital, Newcastle, New South Wales, Australia", 
              "id": "http://www.grid.ac/institutes/grid.413265.7", 
              "name": [
                "Immunology and Oncology Unit, Calvary Mater Newcastle Hospital, Newcastle, New South Wales, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Dong", 
            "givenName": "L", 
            "id": "sg:person.01136142016.09", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01136142016.09"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Immunology and Oncology Unit, Calvary Mater Newcastle Hospital, Newcastle, New South Wales, Australia", 
              "id": "http://www.grid.ac/institutes/grid.413265.7", 
              "name": [
                "Immunology and Oncology Unit, Calvary Mater Newcastle Hospital, Newcastle, New South Wales, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Jiang", 
            "givenName": "C C", 
            "id": "sg:person.0617201523.26", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0617201523.26"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Cancer Research Unit, School of Biomedical Sciences, University of Newcastle, Newcastle, New South Wales, Australia", 
              "id": "http://www.grid.ac/institutes/grid.266842.c", 
              "name": [
                "Cancer Research Unit, School of Biomedical Sciences, University of Newcastle, Newcastle, New South Wales, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Thorne", 
            "givenName": "R F", 
            "id": "sg:person.01210202271.19", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01210202271.19"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Immunology and Oncology Unit, Calvary Mater Newcastle Hospital, Newcastle, New South Wales, Australia", 
              "id": "http://www.grid.ac/institutes/grid.413265.7", 
              "name": [
                "Immunology and Oncology Unit, Calvary Mater Newcastle Hospital, Newcastle, New South Wales, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Croft", 
            "givenName": "A", 
            "id": "sg:person.01215144734.56", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01215144734.56"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Immunology and Oncology Unit, Calvary Mater Newcastle Hospital, Newcastle, New South Wales, Australia", 
              "id": "http://www.grid.ac/institutes/grid.413265.7", 
              "name": [
                "Immunology and Oncology Unit, Calvary Mater Newcastle Hospital, Newcastle, New South Wales, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Yang", 
            "givenName": "F", 
            "id": "sg:person.0755651204.44", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0755651204.44"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Immunology and Oncology Unit, Calvary Mater Newcastle Hospital, Newcastle, New South Wales, Australia", 
              "id": "http://www.grid.ac/institutes/grid.413265.7", 
              "name": [
                "Immunology and Oncology Unit, Calvary Mater Newcastle Hospital, Newcastle, New South Wales, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Liu", 
            "givenName": "H", 
            "id": "sg:person.01212142420.00", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01212142420.00"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Cancer Research Unit, School of Biomedical Sciences, University of Newcastle, Newcastle, New South Wales, Australia", 
              "id": "http://www.grid.ac/institutes/grid.266842.c", 
              "name": [
                "Cancer Research Unit, School of Biomedical Sciences, University of Newcastle, Newcastle, New South Wales, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "de Bock", 
            "givenName": "C E", 
            "id": "sg:person.0577037250.75", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0577037250.75"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Immunology and Oncology Unit, Calvary Mater Newcastle Hospital, Newcastle, New South Wales, Australia", 
              "id": "http://www.grid.ac/institutes/grid.413265.7", 
              "name": [
                "Immunology and Oncology Unit, Calvary Mater Newcastle Hospital, Newcastle, New South Wales, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Hersey", 
            "givenName": "P", 
            "id": "sg:person.01073667716.42", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01073667716.42"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Immunology and Oncology Unit, Calvary Mater Newcastle Hospital, Newcastle, New South Wales, Australia", 
              "id": "http://www.grid.ac/institutes/grid.413265.7", 
              "name": [
                "Immunology and Oncology Unit, Calvary Mater Newcastle Hospital, Newcastle, New South Wales, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Zhang", 
            "givenName": "X D", 
            "id": "sg:person.01210116316.18", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01210116316.18"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/cddis.2010.48", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005879650", 
              "https://doi.org/10.1038/cddis.2010.48"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1206040", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004350012", 
              "https://doi.org/10.1038/sj.onc.1206040"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrc883", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1008451806", 
              "https://doi.org/10.1038/nrc883"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/modpathol.3800206", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029738668", 
              "https://doi.org/10.1038/modpathol.3800206"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/377635a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001155105", 
              "https://doi.org/10.1038/377635a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00018-003-3337-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003057229", 
              "https://doi.org/10.1007/s00018-003-3337-8"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/modpathol.3800750", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022673157", 
              "https://doi.org/10.1038/modpathol.3800750"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1203385", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1052601304", 
              "https://doi.org/10.1038/sj.onc.1203385"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/pl00000728", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1027234006", 
              "https://doi.org/10.1007/pl00000728"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/modpathol.2009.129", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053552098", 
              "https://doi.org/10.1038/modpathol.2009.129"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/1476-4598-8-122", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037487578", 
              "https://doi.org/10.1186/1476-4598-8-122"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature08646", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041625366", 
              "https://doi.org/10.1038/nature08646"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/1476-4598-2-29", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030377110", 
              "https://doi.org/10.1186/1476-4598-2-29"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1211044", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046083984", 
              "https://doi.org/10.1038/sj.onc.1211044"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/cdd.2010.29", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1035034614", 
              "https://doi.org/10.1038/cdd.2010.29"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1206454", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051330539", 
              "https://doi.org/10.1038/sj.onc.1206454"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2011-03-21", 
        "datePublishedReg": "2011-03-21", 
        "description": "Past studies have shown that upregulation of the anti-apoptotic Bcl-2 family protein Mcl-1 is a major adaptive mechanism of melanoma cells to endoplasmic reticulum (ER) stress, and has an important role in resistance of the cells to apoptosis. In this study, we show that the increase in transcription of Mcl-1 in melanoma cells triggered by pharmacological ER stress inducers is mediated by the transcription factor Ets-1. By incremental deletion analysis of the Mcl-1 promoter, we identified a DNA fragment containing an Ets-1 binding site that is transcriptionally responsive to ER stress. Mutations in the Ets-1 binding site or knockdown of Ets-1 inhibited the increase in Mcl-1, indicating that Ets-1 has a critical role in transcriptional upregulation of Mcl-1. Similar to Mcl-1, Ets-1 was transcriptionally upregulated by ER stress. This was mediated by the IRE1\u03b1/XBP-1 branch of the unfolded protein response, as upregulation of Ets-1 was inhibited in melanoma cell lines deficient in IRE1\u03b1 or XBP-1 established by short hairpin RNA knockdown. Activation of the PI3k/Akt pathway downstream of XBP-1 was also involved, in that inhibition of the pathway blocked upregulation of Ets-1. Inhibition of Ets-1 enhanced ER stress-induced apoptosis in melanoma cell lines and in fresh melanoma isolates, recapitulating the effect of inhibition of Mcl-1. These results reveal a key mechanism by which Mcl-1 is transcriptionally upregulated in melanoma cells by ER stress, and identify Ets-1 as a potential target for inhibition to sensitize melanoma cells to apoptosis.", 
        "genre": "article", 
        "id": "sg:pub.10.1038/onc.2011.87", 
        "isAccessibleForFree": true, 
        "isPartOf": [
          {
            "id": "sg:journal.1097543", 
            "issn": [
              "0950-9232", 
              "1476-5594"
            ], 
            "name": "Oncogene", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "34", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "30"
          }
        ], 
        "keywords": [
          "Mcl-1", 
          "ER stress", 
          "XBP-1", 
          "anti-apoptotic Bcl-2 family protein Mcl-1", 
          "Bcl-2 family protein Mcl-1", 
          "melanoma cell lines", 
          "melanoma cells", 
          "transcription factor Ets-1", 
          "short hairpin RNA knockdown", 
          "pharmacological ER stress inducers", 
          "Mcl-1 promoter", 
          "unfolded protein response", 
          "ER stress-induced apoptosis", 
          "protein Mcl-1", 
          "major adaptive mechanism", 
          "stress-induced apoptosis", 
          "cell lines", 
          "ER stress inducers", 
          "PI3K/Akt pathway", 
          "fresh melanoma isolates", 
          "endoplasmic reticulum stress", 
          "deletion analysis", 
          "protein response", 
          "transcriptional upregulation", 
          "RNA knockdown", 
          "DNA fragments", 
          "stress inducers", 
          "human melanoma cells", 
          "Akt pathway", 
          "IRE1\u03b1/XBP", 
          "reticulum stress", 
          "potential target", 
          "adaptive mechanisms", 
          "apoptosis", 
          "ET-1", 
          "knockdown", 
          "critical role", 
          "upregulation", 
          "cells", 
          "key mechanism", 
          "pathway", 
          "inhibition", 
          "effect of inhibition", 
          "important role", 
          "transcription", 
          "promoter", 
          "IRE1\u03b1", 
          "stress", 
          "XBP", 
          "mutations", 
          "sites", 
          "mechanism", 
          "role", 
          "inducer", 
          "lines", 
          "downstream", 
          "fragments", 
          "activation", 
          "isolates", 
          "target", 
          "resistance", 
          "response", 
          "past studies", 
          "increase", 
          "study", 
          "branches", 
          "analysis", 
          "effect", 
          "results"
        ], 
        "name": "Ets-1 mediates upregulation of Mcl-1 downstream of XBP-1 in human melanoma cells upon ER stress", 
        "pagination": "3716-3726", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1039031247"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/onc.2011.87"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "21423203"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/onc.2011.87", 
          "https://app.dimensions.ai/details/publication/pub.1039031247"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-09-02T15:54", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20220902/entities/gbq_results/article/article_536.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1038/onc.2011.87"
      }
    ]
     

    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/onc.2011.87'

    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/onc.2011.87'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/onc.2011.87'

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

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/onc.2011.87'


     

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

    341 TRIPLES      21 PREDICATES      132 URIs      107 LITERALS      28 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/onc.2011.87 schema:about N0cc8f3cfabe54ef2b9c766f0002c4c7d
    2 N129a832b0bf9420b97cf13e611298c88
    3 N1346a71f8f974de0b24a66ffdfd87a9c
    4 N3b8d495e00a44470bc354650d7bf86f4
    5 N3eccd06c822e4e24b7caa0a76e541cc9
    6 N508a1e670de64fb28d2e1aa118ae880a
    7 N553e07f558b045f3931372abd0ec08de
    8 N606eff4f162f4d278471fcf9eb715660
    9 N7ef1cc6eb05740ba811000ecb2c2cf3e
    10 N8bb741fa20a448c1a1236733566f46b3
    11 N98b8958324254339aaa2a5956bbba972
    12 Na2f9305f233141b8940c15ed2d122505
    13 Na6ecfc2bacec40a48b5bdeb0c2aa7dfe
    14 Nc195a5c81e3b48b28fb48deaf0bc37f1
    15 Nc2277fd1e0174ebbb31b5fb204857c0d
    16 Nd1afe7d6b8c14acca8dd5fab78dc87b4
    17 Nd2496695b80846708db90e856775ab18
    18 Ne57c12b1cdf44fecabe7a2e57441584e
    19 Neef2ccd3b54c45fd9051f1a4f2e32942
    20 Nf87692be2a6d49759f8115b3d1947343
    21 Nfa89b4d049054b93ba0b1a32614b7462
    22 anzsrc-for:11
    23 anzsrc-for:1103
    24 anzsrc-for:1112
    25 schema:author Nd05623a53eff4fcb96094bc18c9576a4
    26 schema:citation sg:pub.10.1007/pl00000728
    27 sg:pub.10.1007/s00018-003-3337-8
    28 sg:pub.10.1038/377635a0
    29 sg:pub.10.1038/cdd.2010.29
    30 sg:pub.10.1038/cddis.2010.48
    31 sg:pub.10.1038/modpathol.2009.129
    32 sg:pub.10.1038/modpathol.3800206
    33 sg:pub.10.1038/modpathol.3800750
    34 sg:pub.10.1038/nature08646
    35 sg:pub.10.1038/nrc883
    36 sg:pub.10.1038/sj.onc.1203385
    37 sg:pub.10.1038/sj.onc.1206040
    38 sg:pub.10.1038/sj.onc.1206454
    39 sg:pub.10.1038/sj.onc.1211044
    40 sg:pub.10.1186/1476-4598-2-29
    41 sg:pub.10.1186/1476-4598-8-122
    42 schema:datePublished 2011-03-21
    43 schema:datePublishedReg 2011-03-21
    44 schema:description Past studies have shown that upregulation of the anti-apoptotic Bcl-2 family protein Mcl-1 is a major adaptive mechanism of melanoma cells to endoplasmic reticulum (ER) stress, and has an important role in resistance of the cells to apoptosis. In this study, we show that the increase in transcription of Mcl-1 in melanoma cells triggered by pharmacological ER stress inducers is mediated by the transcription factor Ets-1. By incremental deletion analysis of the Mcl-1 promoter, we identified a DNA fragment containing an Ets-1 binding site that is transcriptionally responsive to ER stress. Mutations in the Ets-1 binding site or knockdown of Ets-1 inhibited the increase in Mcl-1, indicating that Ets-1 has a critical role in transcriptional upregulation of Mcl-1. Similar to Mcl-1, Ets-1 was transcriptionally upregulated by ER stress. This was mediated by the IRE1α/XBP-1 branch of the unfolded protein response, as upregulation of Ets-1 was inhibited in melanoma cell lines deficient in IRE1α or XBP-1 established by short hairpin RNA knockdown. Activation of the PI3k/Akt pathway downstream of XBP-1 was also involved, in that inhibition of the pathway blocked upregulation of Ets-1. Inhibition of Ets-1 enhanced ER stress-induced apoptosis in melanoma cell lines and in fresh melanoma isolates, recapitulating the effect of inhibition of Mcl-1. These results reveal a key mechanism by which Mcl-1 is transcriptionally upregulated in melanoma cells by ER stress, and identify Ets-1 as a potential target for inhibition to sensitize melanoma cells to apoptosis.
    45 schema:genre article
    46 schema:isAccessibleForFree true
    47 schema:isPartOf Nae2a6c614f9e45f99e2f80917e31f52d
    48 Ncc18b136ad0442b494d5f3cff992b1f1
    49 sg:journal.1097543
    50 schema:keywords Akt pathway
    51 Bcl-2 family protein Mcl-1
    52 DNA fragments
    53 ER stress
    54 ER stress inducers
    55 ER stress-induced apoptosis
    56 ET-1
    57 IRE1α
    58 IRE1α/XBP
    59 Mcl-1
    60 Mcl-1 promoter
    61 PI3K/Akt pathway
    62 RNA knockdown
    63 XBP
    64 XBP-1
    65 activation
    66 adaptive mechanisms
    67 analysis
    68 anti-apoptotic Bcl-2 family protein Mcl-1
    69 apoptosis
    70 branches
    71 cell lines
    72 cells
    73 critical role
    74 deletion analysis
    75 downstream
    76 effect
    77 effect of inhibition
    78 endoplasmic reticulum stress
    79 fragments
    80 fresh melanoma isolates
    81 human melanoma cells
    82 important role
    83 increase
    84 inducer
    85 inhibition
    86 isolates
    87 key mechanism
    88 knockdown
    89 lines
    90 major adaptive mechanism
    91 mechanism
    92 melanoma cell lines
    93 melanoma cells
    94 mutations
    95 past studies
    96 pathway
    97 pharmacological ER stress inducers
    98 potential target
    99 promoter
    100 protein Mcl-1
    101 protein response
    102 resistance
    103 response
    104 results
    105 reticulum stress
    106 role
    107 short hairpin RNA knockdown
    108 sites
    109 stress
    110 stress inducers
    111 stress-induced apoptosis
    112 study
    113 target
    114 transcription
    115 transcription factor Ets-1
    116 transcriptional upregulation
    117 unfolded protein response
    118 upregulation
    119 schema:name Ets-1 mediates upregulation of Mcl-1 downstream of XBP-1 in human melanoma cells upon ER stress
    120 schema:pagination 3716-3726
    121 schema:productId N485056b9797747a59b10bb0b805b1ae8
    122 N5f4c1d548c384ffea1d3250bdddc86e1
    123 N94e59bddc0f74641996da0e426456a43
    124 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039031247
    125 https://doi.org/10.1038/onc.2011.87
    126 schema:sdDatePublished 2022-09-02T15:54
    127 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    128 schema:sdPublisher N8c2b918db0584410b8d62a52a6162bc0
    129 schema:url https://doi.org/10.1038/onc.2011.87
    130 sgo:license sg:explorer/license/
    131 sgo:sdDataset articles
    132 rdf:type schema:ScholarlyArticle
    133 N02b5bd84d6074b0da0b22f08e85c0c90 rdf:first sg:person.0755651204.44
    134 rdf:rest N60b1102309e942359db2cc8a0956bd36
    135 N0cc8f3cfabe54ef2b9c766f0002c4c7d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    136 schema:name Transcription, Genetic
    137 rdf:type schema:DefinedTerm
    138 N0e1783d43b1e44ec9de796149131748a rdf:first sg:person.01210202271.19
    139 rdf:rest N172e16b6972d4f439e3ced29482ab9ae
    140 N129a832b0bf9420b97cf13e611298c88 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    141 schema:name Transcription Factors
    142 rdf:type schema:DefinedTerm
    143 N1346a71f8f974de0b24a66ffdfd87a9c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    144 schema:name Electrophoretic Mobility Shift Assay
    145 rdf:type schema:DefinedTerm
    146 N172e16b6972d4f439e3ced29482ab9ae rdf:first sg:person.01215144734.56
    147 rdf:rest N02b5bd84d6074b0da0b22f08e85c0c90
    148 N2a8c4d7735a544508ecad22b383ffd39 rdf:first sg:person.01073667716.42
    149 rdf:rest Ncbc8347ed1a9477f83c2e6448629b319
    150 N347f162e91f24c3a8dea73ef7968096c rdf:first sg:person.0617201523.26
    151 rdf:rest N0e1783d43b1e44ec9de796149131748a
    152 N3b8d495e00a44470bc354650d7bf86f4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    153 schema:name Blotting, Western
    154 rdf:type schema:DefinedTerm
    155 N3eccd06c822e4e24b7caa0a76e541cc9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    156 schema:name Myeloid Cell Leukemia Sequence 1 Protein
    157 rdf:type schema:DefinedTerm
    158 N485056b9797747a59b10bb0b805b1ae8 schema:name pubmed_id
    159 schema:value 21423203
    160 rdf:type schema:PropertyValue
    161 N508a1e670de64fb28d2e1aa118ae880a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    162 schema:name Proto-Oncogene Proteins c-bcl-2
    163 rdf:type schema:DefinedTerm
    164 N553e07f558b045f3931372abd0ec08de schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    165 schema:name Humans
    166 rdf:type schema:DefinedTerm
    167 N5f4c1d548c384ffea1d3250bdddc86e1 schema:name doi
    168 schema:value 10.1038/onc.2011.87
    169 rdf:type schema:PropertyValue
    170 N606eff4f162f4d278471fcf9eb715660 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    171 schema:name DNA-Binding Proteins
    172 rdf:type schema:DefinedTerm
    173 N60b1102309e942359db2cc8a0956bd36 rdf:first sg:person.01212142420.00
    174 rdf:rest Nfeef138f24994a5b9ed4b6d45990523d
    175 N7ef1cc6eb05740ba811000ecb2c2cf3e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    176 schema:name X-Box Binding Protein 1
    177 rdf:type schema:DefinedTerm
    178 N8bb741fa20a448c1a1236733566f46b3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    179 schema:name Polymerase Chain Reaction
    180 rdf:type schema:DefinedTerm
    181 N8c2b918db0584410b8d62a52a6162bc0 schema:name Springer Nature - SN SciGraph project
    182 rdf:type schema:Organization
    183 N94e59bddc0f74641996da0e426456a43 schema:name dimensions_id
    184 schema:value pub.1039031247
    185 rdf:type schema:PropertyValue
    186 N98b8958324254339aaa2a5956bbba972 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    187 schema:name DNA Primers
    188 rdf:type schema:DefinedTerm
    189 Na2f9305f233141b8940c15ed2d122505 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    190 schema:name Promoter Regions, Genetic
    191 rdf:type schema:DefinedTerm
    192 Na6ecfc2bacec40a48b5bdeb0c2aa7dfe schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    193 schema:name Chromatin Immunoprecipitation
    194 rdf:type schema:DefinedTerm
    195 Nae2a6c614f9e45f99e2f80917e31f52d schema:volumeNumber 30
    196 rdf:type schema:PublicationVolume
    197 Nc195a5c81e3b48b28fb48deaf0bc37f1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    198 schema:name Apoptosis
    199 rdf:type schema:DefinedTerm
    200 Nc2277fd1e0174ebbb31b5fb204857c0d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    201 schema:name Cell Line, Tumor
    202 rdf:type schema:DefinedTerm
    203 Ncbc8347ed1a9477f83c2e6448629b319 rdf:first sg:person.01210116316.18
    204 rdf:rest rdf:nil
    205 Ncc18b136ad0442b494d5f3cff992b1f1 schema:issueNumber 34
    206 rdf:type schema:PublicationIssue
    207 Nd05623a53eff4fcb96094bc18c9576a4 rdf:first sg:person.01136142016.09
    208 rdf:rest N347f162e91f24c3a8dea73ef7968096c
    209 Nd1afe7d6b8c14acca8dd5fab78dc87b4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    210 schema:name Melanoma
    211 rdf:type schema:DefinedTerm
    212 Nd2496695b80846708db90e856775ab18 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    213 schema:name Regulatory Factor X Transcription Factors
    214 rdf:type schema:DefinedTerm
    215 Ne57c12b1cdf44fecabe7a2e57441584e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    216 schema:name Proto-Oncogene Protein c-ets-1
    217 rdf:type schema:DefinedTerm
    218 Neef2ccd3b54c45fd9051f1a4f2e32942 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    219 schema:name Base Sequence
    220 rdf:type schema:DefinedTerm
    221 Nf87692be2a6d49759f8115b3d1947343 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    222 schema:name Up-Regulation
    223 rdf:type schema:DefinedTerm
    224 Nfa89b4d049054b93ba0b1a32614b7462 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    225 schema:name Endoplasmic Reticulum
    226 rdf:type schema:DefinedTerm
    227 Nfeef138f24994a5b9ed4b6d45990523d rdf:first sg:person.0577037250.75
    228 rdf:rest N2a8c4d7735a544508ecad22b383ffd39
    229 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    230 schema:name Medical and Health Sciences
    231 rdf:type schema:DefinedTerm
    232 anzsrc-for:1103 schema:inDefinedTermSet anzsrc-for:
    233 schema:name Clinical Sciences
    234 rdf:type schema:DefinedTerm
    235 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
    236 schema:name Oncology and Carcinogenesis
    237 rdf:type schema:DefinedTerm
    238 sg:journal.1097543 schema:issn 0950-9232
    239 1476-5594
    240 schema:name Oncogene
    241 schema:publisher Springer Nature
    242 rdf:type schema:Periodical
    243 sg:person.01073667716.42 schema:affiliation grid-institutes:grid.413265.7
    244 schema:familyName Hersey
    245 schema:givenName P
    246 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01073667716.42
    247 rdf:type schema:Person
    248 sg:person.01136142016.09 schema:affiliation grid-institutes:grid.413265.7
    249 schema:familyName Dong
    250 schema:givenName L
    251 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01136142016.09
    252 rdf:type schema:Person
    253 sg:person.01210116316.18 schema:affiliation grid-institutes:grid.413265.7
    254 schema:familyName Zhang
    255 schema:givenName X D
    256 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01210116316.18
    257 rdf:type schema:Person
    258 sg:person.01210202271.19 schema:affiliation grid-institutes:grid.266842.c
    259 schema:familyName Thorne
    260 schema:givenName R F
    261 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01210202271.19
    262 rdf:type schema:Person
    263 sg:person.01212142420.00 schema:affiliation grid-institutes:grid.413265.7
    264 schema:familyName Liu
    265 schema:givenName H
    266 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01212142420.00
    267 rdf:type schema:Person
    268 sg:person.01215144734.56 schema:affiliation grid-institutes:grid.413265.7
    269 schema:familyName Croft
    270 schema:givenName A
    271 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01215144734.56
    272 rdf:type schema:Person
    273 sg:person.0577037250.75 schema:affiliation grid-institutes:grid.266842.c
    274 schema:familyName de Bock
    275 schema:givenName C E
    276 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0577037250.75
    277 rdf:type schema:Person
    278 sg:person.0617201523.26 schema:affiliation grid-institutes:grid.413265.7
    279 schema:familyName Jiang
    280 schema:givenName C C
    281 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0617201523.26
    282 rdf:type schema:Person
    283 sg:person.0755651204.44 schema:affiliation grid-institutes:grid.413265.7
    284 schema:familyName Yang
    285 schema:givenName F
    286 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0755651204.44
    287 rdf:type schema:Person
    288 sg:pub.10.1007/pl00000728 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027234006
    289 https://doi.org/10.1007/pl00000728
    290 rdf:type schema:CreativeWork
    291 sg:pub.10.1007/s00018-003-3337-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003057229
    292 https://doi.org/10.1007/s00018-003-3337-8
    293 rdf:type schema:CreativeWork
    294 sg:pub.10.1038/377635a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001155105
    295 https://doi.org/10.1038/377635a0
    296 rdf:type schema:CreativeWork
    297 sg:pub.10.1038/cdd.2010.29 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035034614
    298 https://doi.org/10.1038/cdd.2010.29
    299 rdf:type schema:CreativeWork
    300 sg:pub.10.1038/cddis.2010.48 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005879650
    301 https://doi.org/10.1038/cddis.2010.48
    302 rdf:type schema:CreativeWork
    303 sg:pub.10.1038/modpathol.2009.129 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053552098
    304 https://doi.org/10.1038/modpathol.2009.129
    305 rdf:type schema:CreativeWork
    306 sg:pub.10.1038/modpathol.3800206 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029738668
    307 https://doi.org/10.1038/modpathol.3800206
    308 rdf:type schema:CreativeWork
    309 sg:pub.10.1038/modpathol.3800750 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022673157
    310 https://doi.org/10.1038/modpathol.3800750
    311 rdf:type schema:CreativeWork
    312 sg:pub.10.1038/nature08646 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041625366
    313 https://doi.org/10.1038/nature08646
    314 rdf:type schema:CreativeWork
    315 sg:pub.10.1038/nrc883 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008451806
    316 https://doi.org/10.1038/nrc883
    317 rdf:type schema:CreativeWork
    318 sg:pub.10.1038/sj.onc.1203385 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052601304
    319 https://doi.org/10.1038/sj.onc.1203385
    320 rdf:type schema:CreativeWork
    321 sg:pub.10.1038/sj.onc.1206040 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004350012
    322 https://doi.org/10.1038/sj.onc.1206040
    323 rdf:type schema:CreativeWork
    324 sg:pub.10.1038/sj.onc.1206454 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051330539
    325 https://doi.org/10.1038/sj.onc.1206454
    326 rdf:type schema:CreativeWork
    327 sg:pub.10.1038/sj.onc.1211044 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046083984
    328 https://doi.org/10.1038/sj.onc.1211044
    329 rdf:type schema:CreativeWork
    330 sg:pub.10.1186/1476-4598-2-29 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030377110
    331 https://doi.org/10.1186/1476-4598-2-29
    332 rdf:type schema:CreativeWork
    333 sg:pub.10.1186/1476-4598-8-122 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037487578
    334 https://doi.org/10.1186/1476-4598-8-122
    335 rdf:type schema:CreativeWork
    336 grid-institutes:grid.266842.c schema:alternateName Cancer Research Unit, School of Biomedical Sciences, University of Newcastle, Newcastle, New South Wales, Australia
    337 schema:name Cancer Research Unit, School of Biomedical Sciences, University of Newcastle, Newcastle, New South Wales, Australia
    338 rdf:type schema:Organization
    339 grid-institutes:grid.413265.7 schema:alternateName Immunology and Oncology Unit, Calvary Mater Newcastle Hospital, Newcastle, New South Wales, Australia
    340 schema:name Immunology and Oncology Unit, Calvary Mater Newcastle Hospital, Newcastle, New South Wales, Australia
    341 rdf:type schema:Organization
     




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


    ...