Mutations in the PKM2 exon-10 region are associated with reduced allostery and increased nuclear translocation View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-12

AUTHORS

Tsan-Jan Chen, Hung-Jung Wang, Jai-Shin Liu, Hsin-Hung Cheng, Sheng-Chieh Hsu, Meng-Chen Wu, Chien-Hung Lu, Yu-Fang Wu, Jing-Wen Wu, Ying-Yuan Liu, Hsing-Jien Kung, Wen-Ching Wang

ABSTRACT

PKM2 is a key metabolic enzyme central to glucose metabolism and energy expenditure. Multiple stimuli regulate PKM2's activity through allosteric modulation and post-translational modifications. Furthermore, PKM2 can partner with KDM8, an oncogenic demethylase and enter the nucleus to serve as a HIF1α co-activator. Yet, the mechanistic basis of the exon-10 region in allosteric regulation and nuclear translocation remains unclear. Here, we determined the crystal structures and kinetic coupling constants of exon-10 tumor-related mutants (H391Y and R399E), showing altered structural plasticity and reduced allostery. Immunoprecipitation analysis revealed increased interaction with KDM8 for H391Y, R399E, and G415R. We also found a higher degree of HIF1α-mediated transactivation activity, particularly in the presence of KDM8. Furthermore, overexpression of PKM2 mutants significantly elevated cell growth and migration. Together, PKM2 exon-10 mutations lead to structure-allostery alterations and increased nuclear functions mediated by KDM8 in breast cancer cells. Targeting the PKM2-KDM8 complex may provide a potential therapeutic intervention. More... »

PAGES

105

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s42003-019-0343-4

DOI

http://dx.doi.org/10.1038/s42003-019-0343-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112759339

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30911680


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"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "National Tsing Hua University", 
          "id": "https://www.grid.ac/institutes/grid.38348.34", 
          "name": [
            "Institute of Molecular and Cellular Biology and Department of Life Science, National Tsing-Hua University, 30013, Hsinchu, Taiwan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Chen", 
        "givenName": "Tsan-Jan", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "National Health Research Institutes", 
          "id": "https://www.grid.ac/institutes/grid.59784.37", 
          "name": [
            "Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35053, Miaoli, Taiwan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wang", 
        "givenName": "Hung-Jung", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "National Tsing Hua University", 
          "id": "https://www.grid.ac/institutes/grid.38348.34", 
          "name": [
            "Institute of Molecular and Cellular Biology and Department of Life Science, National Tsing-Hua University, 30013, Hsinchu, Taiwan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Liu", 
        "givenName": "Jai-Shin", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "National Tsing Hua University", 
          "id": "https://www.grid.ac/institutes/grid.38348.34", 
          "name": [
            "Institute of Molecular and Cellular Biology and Department of Life Science, National Tsing-Hua University, 30013, Hsinchu, Taiwan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Cheng", 
        "givenName": "Hsin-Hung", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "National Tsing Hua University", 
          "id": "https://www.grid.ac/institutes/grid.38348.34", 
          "name": [
            "Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35053, Miaoli, Taiwan", 
            "Institute of Biotechnology, National Tsing-Hua University, 30013, Hsinchu, Taiwan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Hsu", 
        "givenName": "Sheng-Chieh", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "National Tsing Hua University", 
          "id": "https://www.grid.ac/institutes/grid.38348.34", 
          "name": [
            "Institute of Molecular and Cellular Biology and Department of Life Science, National Tsing-Hua University, 30013, Hsinchu, Taiwan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wu", 
        "givenName": "Meng-Chen", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "National Tsing Hua University", 
          "id": "https://www.grid.ac/institutes/grid.38348.34", 
          "name": [
            "Institute of Molecular and Cellular Biology and Department of Life Science, National Tsing-Hua University, 30013, Hsinchu, Taiwan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Lu", 
        "givenName": "Chien-Hung", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "National Tsing Hua University", 
          "id": "https://www.grid.ac/institutes/grid.38348.34", 
          "name": [
            "Institute of Molecular and Cellular Biology and Department of Life Science, National Tsing-Hua University, 30013, Hsinchu, Taiwan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wu", 
        "givenName": "Yu-Fang", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "National Tsing Hua University", 
          "id": "https://www.grid.ac/institutes/grid.38348.34", 
          "name": [
            "Institute of Molecular and Cellular Biology and Department of Life Science, National Tsing-Hua University, 30013, Hsinchu, Taiwan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wu", 
        "givenName": "Jing-Wen", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "National Tsing Hua University", 
          "id": "https://www.grid.ac/institutes/grid.38348.34", 
          "name": [
            "Institute of Molecular and Cellular Biology and Department of Life Science, National Tsing-Hua University, 30013, Hsinchu, Taiwan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Liu", 
        "givenName": "Ying-Yuan", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California, Davis", 
          "id": "https://www.grid.ac/institutes/grid.27860.3b", 
          "name": [
            "Institute of Molecular and Genomic Medicine, National Health Research Institutes, 35053, Miaoli, Taiwan", 
            "Department of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, University of California Davis Cancer Centre, 95817, Sacramento, CA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kung", 
        "givenName": "Hsing-Jien", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "National Tsing Hua University", 
          "id": "https://www.grid.ac/institutes/grid.38348.34", 
          "name": [
            "Institute of Molecular and Cellular Biology and Department of Life Science, National Tsing-Hua University, 30013, Hsinchu, Taiwan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wang", 
        "givenName": "Wen-Ching", 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1038/nature11540", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000007436", 
          "https://doi.org/10.1038/nature11540"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.1000401107", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000131697"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.biocel.2010.02.005", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000361938"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.molcel.2013.11.001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002548074"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.biochi.2013.08.002", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003445823"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.bbcan.2014.07.008", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003744485"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1242/dev.074138", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010812352"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/2159-8290.cd-12-0095", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011831914"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.chembiol.2012.07.021", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014284406"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature10983", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014607335", 
          "https://doi.org/10.1038/nature10983"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cell.2013.09.025", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015362108"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s13238-015-0132-x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016057142", 
          "https://doi.org/10.1007/s13238-015-0132-x"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/scisignal.2000431", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017604614"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.15252/embr.201643300", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018569335"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cell.2012.07.018", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023853635"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.18632/oncotarget.4448", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025683781"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/onc.2013.119", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026319098", 
          "https://doi.org/10.1038/onc.2013.119"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/onc.2013.119", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026319098", 
          "https://doi.org/10.1038/onc.2013.119"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.molcel.2011.04.025", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026585387"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/stem.1724", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029334298"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature10598", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030215402", 
          "https://doi.org/10.1038/nature10598"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature10598", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030215402", 
          "https://doi.org/10.1038/nature10598"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature06667", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030770844", 
          "https://doi.org/10.1038/nature06667"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.molcel.2013.09.004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033002332"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1160809", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033271739"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1160809", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033271739"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cell.2011.03.054", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033487900"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/scisignal.2004088", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033807182"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ncomms6566", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036005919", 
          "https://doi.org/10.1038/ncomms6566"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.18632/oncotarget.1159", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036381318"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.1217157110", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037876748"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.1311249111", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040017143"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.molcel.2012.01.001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040146201"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nchembio.1060", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041031209", 
          "https://doi.org/10.1038/nchembio.1060"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m700094200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044087177"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m113.515742", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044736403"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1211485", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047887177"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.semcancer.2005.04.009", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048241986"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.semcancer.2005.04.009", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048241986"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.febslet.2014.04.011", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048339869"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/mcb.00513-12", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049728635"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.celrep.2016.03.070", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049904355"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1042/bst0331456", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051302697"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1042/bst0331456", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051302697"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.bbrc.2012.02.115", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052065179"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrc2981", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052273406", 
          "https://doi.org/10.1038/nrc2981"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/bi00346a022", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055171263"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/bi0474923", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055198562"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/bi0474923", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055198562"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/bi401402j", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055206316"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1089/1044549041474797", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1059203876"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1224409", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1062466830"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1080637599", 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ncb3630", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1092350565", 
          "https://doi.org/10.1038/ncb3630"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ncb3630", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1092350565", 
          "https://doi.org/10.1038/ncb3630"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2019-12", 
    "datePublishedReg": "2019-12-01", 
    "description": "PKM2 is a key metabolic enzyme central to glucose metabolism and energy expenditure. Multiple stimuli regulate PKM2's activity through allosteric modulation and post-translational modifications. Furthermore, PKM2 can partner with KDM8, an oncogenic demethylase and enter the nucleus to serve as a HIF1\u03b1 co-activator. Yet, the mechanistic basis of the exon-10 region in allosteric regulation and nuclear translocation remains unclear. Here, we determined the\u00a0crystal structures and kinetic coupling constants of exon-10 tumor-related mutants (H391Y and R399E), showing altered structural plasticity and reduced allostery. Immunoprecipitation analysis revealed increased interaction with KDM8 for H391Y, R399E, and G415R. We also found a higher degree of HIF1\u03b1-mediated transactivation activity, particularly in the presence of KDM8. Furthermore, overexpression of PKM2 mutants significantly elevated cell growth and migration. Together, PKM2 exon-10 mutations lead to structure-allostery alterations and increased nuclear functions mediated by KDM8 in breast cancer cells. Targeting the PKM2-KDM8 complex may provide a potential therapeutic intervention.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/s42003-019-0343-4", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": false, 
    "isPartOf": [
      {
        "id": "sg:journal.1300829", 
        "issn": [
          "2399-3642"
        ], 
        "name": "Communications Biology", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "2"
      }
    ], 
    "name": "Mutations in the PKM2 exon-10 region are associated with reduced allostery and increased nuclear translocation", 
    "pagination": "105", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "1a84f7b75f2e64f93b96f4610b6c2cb835286e626039d43cb7b9c25a5f97f0fe"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "30911680"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "101719179"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/s42003-019-0343-4"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1112759339"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/s42003-019-0343-4", 
      "https://app.dimensions.ai/details/publication/pub.1112759339"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T13:55", 
    "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/v90/0000000371_0000000371/records_130811_00000006.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://www.nature.com/articles/s42003-019-0343-4"
  }
]
 

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/s42003-019-0343-4'

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/s42003-019-0343-4'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s42003-019-0343-4'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s42003-019-0343-4'


 

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

295 TRIPLES      21 PREDICATES      77 URIs      21 LITERALS      9 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/s42003-019-0343-4 schema:about anzsrc-for:06
2 anzsrc-for:0601
3 schema:author Nd95714c6d6e14c159d7481339510b3a5
4 schema:citation sg:pub.10.1007/s13238-015-0132-x
5 sg:pub.10.1038/nature06667
6 sg:pub.10.1038/nature10598
7 sg:pub.10.1038/nature10983
8 sg:pub.10.1038/nature11540
9 sg:pub.10.1038/ncb3630
10 sg:pub.10.1038/nchembio.1060
11 sg:pub.10.1038/ncomms6566
12 sg:pub.10.1038/nrc2981
13 sg:pub.10.1038/onc.2013.119
14 https://app.dimensions.ai/details/publication/pub.1080637599
15 https://doi.org/10.1002/stem.1724
16 https://doi.org/10.1016/j.bbcan.2014.07.008
17 https://doi.org/10.1016/j.bbrc.2012.02.115
18 https://doi.org/10.1016/j.biocel.2010.02.005
19 https://doi.org/10.1016/j.biochi.2013.08.002
20 https://doi.org/10.1016/j.cell.2011.03.054
21 https://doi.org/10.1016/j.cell.2012.07.018
22 https://doi.org/10.1016/j.cell.2013.09.025
23 https://doi.org/10.1016/j.celrep.2016.03.070
24 https://doi.org/10.1016/j.chembiol.2012.07.021
25 https://doi.org/10.1016/j.febslet.2014.04.011
26 https://doi.org/10.1016/j.molcel.2011.04.025
27 https://doi.org/10.1016/j.molcel.2012.01.001
28 https://doi.org/10.1016/j.molcel.2013.09.004
29 https://doi.org/10.1016/j.molcel.2013.11.001
30 https://doi.org/10.1016/j.semcancer.2005.04.009
31 https://doi.org/10.1021/bi00346a022
32 https://doi.org/10.1021/bi0474923
33 https://doi.org/10.1021/bi401402j
34 https://doi.org/10.1042/bst0331456
35 https://doi.org/10.1073/pnas.1000401107
36 https://doi.org/10.1073/pnas.1217157110
37 https://doi.org/10.1073/pnas.1311249111
38 https://doi.org/10.1074/jbc.m113.515742
39 https://doi.org/10.1074/jbc.m700094200
40 https://doi.org/10.1089/1044549041474797
41 https://doi.org/10.1126/science.1160809
42 https://doi.org/10.1126/science.1211485
43 https://doi.org/10.1126/science.1224409
44 https://doi.org/10.1126/scisignal.2000431
45 https://doi.org/10.1126/scisignal.2004088
46 https://doi.org/10.1128/mcb.00513-12
47 https://doi.org/10.1158/2159-8290.cd-12-0095
48 https://doi.org/10.1242/dev.074138
49 https://doi.org/10.15252/embr.201643300
50 https://doi.org/10.18632/oncotarget.1159
51 https://doi.org/10.18632/oncotarget.4448
52 schema:datePublished 2019-12
53 schema:datePublishedReg 2019-12-01
54 schema:description PKM2 is a key metabolic enzyme central to glucose metabolism and energy expenditure. Multiple stimuli regulate PKM2's activity through allosteric modulation and post-translational modifications. Furthermore, PKM2 can partner with KDM8, an oncogenic demethylase and enter the nucleus to serve as a HIF1α co-activator. Yet, the mechanistic basis of the exon-10 region in allosteric regulation and nuclear translocation remains unclear. Here, we determined the crystal structures and kinetic coupling constants of exon-10 tumor-related mutants (H391Y and R399E), showing altered structural plasticity and reduced allostery. Immunoprecipitation analysis revealed increased interaction with KDM8 for H391Y, R399E, and G415R. We also found a higher degree of HIF1α-mediated transactivation activity, particularly in the presence of KDM8. Furthermore, overexpression of PKM2 mutants significantly elevated cell growth and migration. Together, PKM2 exon-10 mutations lead to structure-allostery alterations and increased nuclear functions mediated by KDM8 in breast cancer cells. Targeting the PKM2-KDM8 complex may provide a potential therapeutic intervention.
55 schema:genre research_article
56 schema:inLanguage en
57 schema:isAccessibleForFree false
58 schema:isPartOf N054accfec03f449ab23c9a0c3762a116
59 N4ecf60a382444aef805f33ec09a4bc21
60 sg:journal.1300829
61 schema:name Mutations in the PKM2 exon-10 region are associated with reduced allostery and increased nuclear translocation
62 schema:pagination 105
63 schema:productId N1402ffa24ae5431eba6781a54f41b744
64 N597970cf57ac4477b0df66513ff47f09
65 Na46b37ed79e345aeb7dae652fdeba443
66 Nbc1ab9c9bdf342528541a7e9bfd3cb00
67 Nde9d11c379e143cbb589f5191f5f1e8f
68 schema:sameAs https://app.dimensions.ai/details/publication/pub.1112759339
69 https://doi.org/10.1038/s42003-019-0343-4
70 schema:sdDatePublished 2019-04-11T13:55
71 schema:sdLicense https://scigraph.springernature.com/explorer/license/
72 schema:sdPublisher Ncf0841a32fea468f8c558f4ba93f2f9d
73 schema:url https://www.nature.com/articles/s42003-019-0343-4
74 sgo:license sg:explorer/license/
75 sgo:sdDataset articles
76 rdf:type schema:ScholarlyArticle
77 N054accfec03f449ab23c9a0c3762a116 schema:volumeNumber 2
78 rdf:type schema:PublicationVolume
79 N12302b710efe4b4e99144468e61e50c2 schema:affiliation https://www.grid.ac/institutes/grid.27860.3b
80 schema:familyName Kung
81 schema:givenName Hsing-Jien
82 rdf:type schema:Person
83 N13d4669608cc4917b0b176eb8e0249bf schema:affiliation https://www.grid.ac/institutes/grid.38348.34
84 schema:familyName Wu
85 schema:givenName Jing-Wen
86 rdf:type schema:Person
87 N1402ffa24ae5431eba6781a54f41b744 schema:name doi
88 schema:value 10.1038/s42003-019-0343-4
89 rdf:type schema:PropertyValue
90 N278cc292ada8422eb176c9bba54fdfbb schema:affiliation https://www.grid.ac/institutes/grid.38348.34
91 schema:familyName Wu
92 schema:givenName Yu-Fang
93 rdf:type schema:Person
94 N4c0da6f554804375b7ef621b318cdd49 schema:affiliation https://www.grid.ac/institutes/grid.38348.34
95 schema:familyName Lu
96 schema:givenName Chien-Hung
97 rdf:type schema:Person
98 N4da2b14e0ac14c8596666fdb3a55ede9 schema:affiliation https://www.grid.ac/institutes/grid.38348.34
99 schema:familyName Hsu
100 schema:givenName Sheng-Chieh
101 rdf:type schema:Person
102 N4ecf60a382444aef805f33ec09a4bc21 schema:issueNumber 1
103 rdf:type schema:PublicationIssue
104 N597970cf57ac4477b0df66513ff47f09 schema:name pubmed_id
105 schema:value 30911680
106 rdf:type schema:PropertyValue
107 N5a67dbb1dec4402c96132b6a21010068 schema:affiliation https://www.grid.ac/institutes/grid.38348.34
108 schema:familyName Liu
109 schema:givenName Ying-Yuan
110 rdf:type schema:Person
111 N72e630fb91ad404699c5a633a7f9f59a rdf:first Nf08c9e71965144b084218cb8169d7946
112 rdf:rest rdf:nil
113 N74dc8206c5124fe2b8d4205fb68ab59a rdf:first Nc9170d9ce14e45b799d9b011163d1ff2
114 rdf:rest Nc2bc3d69d9714a649c55044504753ef9
115 N792979a48316419ebe14ea9586fa7fde rdf:first N13d4669608cc4917b0b176eb8e0249bf
116 rdf:rest Ne28058a7cd3141f8843b461846788be3
117 N8eb17f2cb91948e8a84df1dfd304fa3c rdf:first N12302b710efe4b4e99144468e61e50c2
118 rdf:rest N72e630fb91ad404699c5a633a7f9f59a
119 N91a9b6d48fa1425abace4233d14b3221 rdf:first Nc332b1eaf0c54055a1a3944047951484
120 rdf:rest Nd7cc18d3c37c4bc39f5d3bb5b251e75b
121 Na46b37ed79e345aeb7dae652fdeba443 schema:name nlm_unique_id
122 schema:value 101719179
123 rdf:type schema:PropertyValue
124 Naeaea48c277b451b94d881fdd3f23eb7 schema:affiliation https://www.grid.ac/institutes/grid.38348.34
125 schema:familyName Cheng
126 schema:givenName Hsin-Hung
127 rdf:type schema:Person
128 Nbc1ab9c9bdf342528541a7e9bfd3cb00 schema:name readcube_id
129 schema:value 1a84f7b75f2e64f93b96f4610b6c2cb835286e626039d43cb7b9c25a5f97f0fe
130 rdf:type schema:PropertyValue
131 Nbe487a33566a4d1b88f2ae3c4c5818d8 rdf:first N278cc292ada8422eb176c9bba54fdfbb
132 rdf:rest N792979a48316419ebe14ea9586fa7fde
133 Nc2bc3d69d9714a649c55044504753ef9 rdf:first Ne6f700344d934532b05da92a5a20ebab
134 rdf:rest Nd498915b1cf74e1e9b9f596dd818f770
135 Nc332b1eaf0c54055a1a3944047951484 schema:affiliation https://www.grid.ac/institutes/grid.38348.34
136 schema:familyName Wu
137 schema:givenName Meng-Chen
138 rdf:type schema:Person
139 Nc9170d9ce14e45b799d9b011163d1ff2 schema:affiliation https://www.grid.ac/institutes/grid.59784.37
140 schema:familyName Wang
141 schema:givenName Hung-Jung
142 rdf:type schema:Person
143 Ncf0841a32fea468f8c558f4ba93f2f9d schema:name Springer Nature - SN SciGraph project
144 rdf:type schema:Organization
145 Nd498915b1cf74e1e9b9f596dd818f770 rdf:first Naeaea48c277b451b94d881fdd3f23eb7
146 rdf:rest Nf31daf7017a7478e8332abc443be3dbf
147 Nd7cc18d3c37c4bc39f5d3bb5b251e75b rdf:first N4c0da6f554804375b7ef621b318cdd49
148 rdf:rest Nbe487a33566a4d1b88f2ae3c4c5818d8
149 Nd95714c6d6e14c159d7481339510b3a5 rdf:first Ne5f9048bd0e14d3a88af011ac0c4871e
150 rdf:rest N74dc8206c5124fe2b8d4205fb68ab59a
151 Nde9d11c379e143cbb589f5191f5f1e8f schema:name dimensions_id
152 schema:value pub.1112759339
153 rdf:type schema:PropertyValue
154 Ne28058a7cd3141f8843b461846788be3 rdf:first N5a67dbb1dec4402c96132b6a21010068
155 rdf:rest N8eb17f2cb91948e8a84df1dfd304fa3c
156 Ne5f9048bd0e14d3a88af011ac0c4871e schema:affiliation https://www.grid.ac/institutes/grid.38348.34
157 schema:familyName Chen
158 schema:givenName Tsan-Jan
159 rdf:type schema:Person
160 Ne6f700344d934532b05da92a5a20ebab schema:affiliation https://www.grid.ac/institutes/grid.38348.34
161 schema:familyName Liu
162 schema:givenName Jai-Shin
163 rdf:type schema:Person
164 Nf08c9e71965144b084218cb8169d7946 schema:affiliation https://www.grid.ac/institutes/grid.38348.34
165 schema:familyName Wang
166 schema:givenName Wen-Ching
167 rdf:type schema:Person
168 Nf31daf7017a7478e8332abc443be3dbf rdf:first N4da2b14e0ac14c8596666fdb3a55ede9
169 rdf:rest N91a9b6d48fa1425abace4233d14b3221
170 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
171 schema:name Biological Sciences
172 rdf:type schema:DefinedTerm
173 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
174 schema:name Biochemistry and Cell Biology
175 rdf:type schema:DefinedTerm
176 sg:journal.1300829 schema:issn 2399-3642
177 schema:name Communications Biology
178 rdf:type schema:Periodical
179 sg:pub.10.1007/s13238-015-0132-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1016057142
180 https://doi.org/10.1007/s13238-015-0132-x
181 rdf:type schema:CreativeWork
182 sg:pub.10.1038/nature06667 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030770844
183 https://doi.org/10.1038/nature06667
184 rdf:type schema:CreativeWork
185 sg:pub.10.1038/nature10598 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030215402
186 https://doi.org/10.1038/nature10598
187 rdf:type schema:CreativeWork
188 sg:pub.10.1038/nature10983 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014607335
189 https://doi.org/10.1038/nature10983
190 rdf:type schema:CreativeWork
191 sg:pub.10.1038/nature11540 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000007436
192 https://doi.org/10.1038/nature11540
193 rdf:type schema:CreativeWork
194 sg:pub.10.1038/ncb3630 schema:sameAs https://app.dimensions.ai/details/publication/pub.1092350565
195 https://doi.org/10.1038/ncb3630
196 rdf:type schema:CreativeWork
197 sg:pub.10.1038/nchembio.1060 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041031209
198 https://doi.org/10.1038/nchembio.1060
199 rdf:type schema:CreativeWork
200 sg:pub.10.1038/ncomms6566 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036005919
201 https://doi.org/10.1038/ncomms6566
202 rdf:type schema:CreativeWork
203 sg:pub.10.1038/nrc2981 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052273406
204 https://doi.org/10.1038/nrc2981
205 rdf:type schema:CreativeWork
206 sg:pub.10.1038/onc.2013.119 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026319098
207 https://doi.org/10.1038/onc.2013.119
208 rdf:type schema:CreativeWork
209 https://app.dimensions.ai/details/publication/pub.1080637599 schema:CreativeWork
210 https://doi.org/10.1002/stem.1724 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029334298
211 rdf:type schema:CreativeWork
212 https://doi.org/10.1016/j.bbcan.2014.07.008 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003744485
213 rdf:type schema:CreativeWork
214 https://doi.org/10.1016/j.bbrc.2012.02.115 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052065179
215 rdf:type schema:CreativeWork
216 https://doi.org/10.1016/j.biocel.2010.02.005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000361938
217 rdf:type schema:CreativeWork
218 https://doi.org/10.1016/j.biochi.2013.08.002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003445823
219 rdf:type schema:CreativeWork
220 https://doi.org/10.1016/j.cell.2011.03.054 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033487900
221 rdf:type schema:CreativeWork
222 https://doi.org/10.1016/j.cell.2012.07.018 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023853635
223 rdf:type schema:CreativeWork
224 https://doi.org/10.1016/j.cell.2013.09.025 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015362108
225 rdf:type schema:CreativeWork
226 https://doi.org/10.1016/j.celrep.2016.03.070 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049904355
227 rdf:type schema:CreativeWork
228 https://doi.org/10.1016/j.chembiol.2012.07.021 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014284406
229 rdf:type schema:CreativeWork
230 https://doi.org/10.1016/j.febslet.2014.04.011 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048339869
231 rdf:type schema:CreativeWork
232 https://doi.org/10.1016/j.molcel.2011.04.025 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026585387
233 rdf:type schema:CreativeWork
234 https://doi.org/10.1016/j.molcel.2012.01.001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040146201
235 rdf:type schema:CreativeWork
236 https://doi.org/10.1016/j.molcel.2013.09.004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033002332
237 rdf:type schema:CreativeWork
238 https://doi.org/10.1016/j.molcel.2013.11.001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002548074
239 rdf:type schema:CreativeWork
240 https://doi.org/10.1016/j.semcancer.2005.04.009 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048241986
241 rdf:type schema:CreativeWork
242 https://doi.org/10.1021/bi00346a022 schema:sameAs https://app.dimensions.ai/details/publication/pub.1055171263
243 rdf:type schema:CreativeWork
244 https://doi.org/10.1021/bi0474923 schema:sameAs https://app.dimensions.ai/details/publication/pub.1055198562
245 rdf:type schema:CreativeWork
246 https://doi.org/10.1021/bi401402j schema:sameAs https://app.dimensions.ai/details/publication/pub.1055206316
247 rdf:type schema:CreativeWork
248 https://doi.org/10.1042/bst0331456 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051302697
249 rdf:type schema:CreativeWork
250 https://doi.org/10.1073/pnas.1000401107 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000131697
251 rdf:type schema:CreativeWork
252 https://doi.org/10.1073/pnas.1217157110 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037876748
253 rdf:type schema:CreativeWork
254 https://doi.org/10.1073/pnas.1311249111 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040017143
255 rdf:type schema:CreativeWork
256 https://doi.org/10.1074/jbc.m113.515742 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044736403
257 rdf:type schema:CreativeWork
258 https://doi.org/10.1074/jbc.m700094200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044087177
259 rdf:type schema:CreativeWork
260 https://doi.org/10.1089/1044549041474797 schema:sameAs https://app.dimensions.ai/details/publication/pub.1059203876
261 rdf:type schema:CreativeWork
262 https://doi.org/10.1126/science.1160809 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033271739
263 rdf:type schema:CreativeWork
264 https://doi.org/10.1126/science.1211485 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047887177
265 rdf:type schema:CreativeWork
266 https://doi.org/10.1126/science.1224409 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062466830
267 rdf:type schema:CreativeWork
268 https://doi.org/10.1126/scisignal.2000431 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017604614
269 rdf:type schema:CreativeWork
270 https://doi.org/10.1126/scisignal.2004088 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033807182
271 rdf:type schema:CreativeWork
272 https://doi.org/10.1128/mcb.00513-12 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049728635
273 rdf:type schema:CreativeWork
274 https://doi.org/10.1158/2159-8290.cd-12-0095 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011831914
275 rdf:type schema:CreativeWork
276 https://doi.org/10.1242/dev.074138 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010812352
277 rdf:type schema:CreativeWork
278 https://doi.org/10.15252/embr.201643300 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018569335
279 rdf:type schema:CreativeWork
280 https://doi.org/10.18632/oncotarget.1159 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036381318
281 rdf:type schema:CreativeWork
282 https://doi.org/10.18632/oncotarget.4448 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025683781
283 rdf:type schema:CreativeWork
284 https://www.grid.ac/institutes/grid.27860.3b schema:alternateName University of California, Davis
285 schema:name Department of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, University of California Davis Cancer Centre, 95817, Sacramento, CA, USA
286 Institute of Molecular and Genomic Medicine, National Health Research Institutes, 35053, Miaoli, Taiwan
287 rdf:type schema:Organization
288 https://www.grid.ac/institutes/grid.38348.34 schema:alternateName National Tsing Hua University
289 schema:name Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35053, Miaoli, Taiwan
290 Institute of Biotechnology, National Tsing-Hua University, 30013, Hsinchu, Taiwan
291 Institute of Molecular and Cellular Biology and Department of Life Science, National Tsing-Hua University, 30013, Hsinchu, Taiwan
292 rdf:type schema:Organization
293 https://www.grid.ac/institutes/grid.59784.37 schema:alternateName National Health Research Institutes
294 schema:name Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35053, Miaoli, Taiwan
295 rdf:type schema:Organization
 




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


...