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 N0316e2069e074a82910681f00af6a67a
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 N6630b2ddfd214527a03fd5fd5254124b
59 Ne2c82db1f5324a04a5e43656fd1e3398
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 Na4612e4be7324773bb60deb38d4972d5
64 Nc0304fed66a14f58a99bd304d1cae6f1
65 Nd2e8b406c69143bd9064c46cc5f055a5
66 Nf11d967cefe14e98847da656450d943e
67 Nf59c5d17310e49f2adf18aecc2c6de51
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 Ne5a594af7b894bffa0864a132633f136
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 N0316e2069e074a82910681f00af6a67a rdf:first N309643b25a004f00824e7b14a199ffb6
78 rdf:rest N58b26257933645afa0ef0a9b81175c9d
79 N1fc6bb5ab99e4e2f926d3a1fb9520bfd schema:affiliation https://www.grid.ac/institutes/grid.38348.34
80 schema:familyName Cheng
81 schema:givenName Hsin-Hung
82 rdf:type schema:Person
83 N225632d542714f05953750d3a3e28292 schema:affiliation https://www.grid.ac/institutes/grid.27860.3b
84 schema:familyName Kung
85 schema:givenName Hsing-Jien
86 rdf:type schema:Person
87 N228fd1dff3024f1c8ccb9e603e2f0ded rdf:first Nb90cdebb67354f54bb6b9ff7cd8f98fd
88 rdf:rest N908893f9c7b146e9ace68343c61f1eaa
89 N2f2c27a3a18a4acbaa574b7573ffc6d7 schema:affiliation https://www.grid.ac/institutes/grid.38348.34
90 schema:familyName Wang
91 schema:givenName Wen-Ching
92 rdf:type schema:Person
93 N3030eff55001419abb33fd2189a01dcf rdf:first N4f10dc7e4be045b4977f2bcc934d0055
94 rdf:rest N228fd1dff3024f1c8ccb9e603e2f0ded
95 N309643b25a004f00824e7b14a199ffb6 schema:affiliation https://www.grid.ac/institutes/grid.38348.34
96 schema:familyName Chen
97 schema:givenName Tsan-Jan
98 rdf:type schema:Person
99 N3bf739a490f34766904a9429a46406b4 schema:affiliation https://www.grid.ac/institutes/grid.38348.34
100 schema:familyName Hsu
101 schema:givenName Sheng-Chieh
102 rdf:type schema:Person
103 N4f10dc7e4be045b4977f2bcc934d0055 schema:affiliation https://www.grid.ac/institutes/grid.38348.34
104 schema:familyName Wu
105 schema:givenName Yu-Fang
106 rdf:type schema:Person
107 N4f5cbd69cae54490b41ebfaf6b9dd795 rdf:first N5957af9387bc4cd1a1d4d2ad6b8272ba
108 rdf:rest Ndfd8e04b8ee2416a8ba9a5e74765a3b2
109 N5722525913924f7caac399e2f2f369b7 rdf:first N9577a99ae2b54e85bbf4b0f6c0e36a34
110 rdf:rest Nf26f36e90bfb471880bcd2eee6b586aa
111 N58b26257933645afa0ef0a9b81175c9d rdf:first N7f9b799a74d84b41a89848734271e18f
112 rdf:rest N4f5cbd69cae54490b41ebfaf6b9dd795
113 N5957af9387bc4cd1a1d4d2ad6b8272ba schema:affiliation https://www.grid.ac/institutes/grid.38348.34
114 schema:familyName Liu
115 schema:givenName Jai-Shin
116 rdf:type schema:Person
117 N6630b2ddfd214527a03fd5fd5254124b schema:issueNumber 1
118 rdf:type schema:PublicationIssue
119 N6a374eeddc394794a058a28aad8946eb schema:affiliation https://www.grid.ac/institutes/grid.38348.34
120 schema:familyName Liu
121 schema:givenName Ying-Yuan
122 rdf:type schema:Person
123 N6a47c731cba54866ba11d4ab1c133a66 schema:affiliation https://www.grid.ac/institutes/grid.38348.34
124 schema:familyName Lu
125 schema:givenName Chien-Hung
126 rdf:type schema:Person
127 N7f9b799a74d84b41a89848734271e18f schema:affiliation https://www.grid.ac/institutes/grid.59784.37
128 schema:familyName Wang
129 schema:givenName Hung-Jung
130 rdf:type schema:Person
131 N908893f9c7b146e9ace68343c61f1eaa rdf:first N6a374eeddc394794a058a28aad8946eb
132 rdf:rest Nd9716eb8d1b542459dea1b2b59e3ece9
133 N9577a99ae2b54e85bbf4b0f6c0e36a34 schema:affiliation https://www.grid.ac/institutes/grid.38348.34
134 schema:familyName Wu
135 schema:givenName Meng-Chen
136 rdf:type schema:Person
137 N980265e0ba0d47e090f465db03a9537b rdf:first N2f2c27a3a18a4acbaa574b7573ffc6d7
138 rdf:rest rdf:nil
139 Na4612e4be7324773bb60deb38d4972d5 schema:name dimensions_id
140 schema:value pub.1112759339
141 rdf:type schema:PropertyValue
142 Nb90cdebb67354f54bb6b9ff7cd8f98fd schema:affiliation https://www.grid.ac/institutes/grid.38348.34
143 schema:familyName Wu
144 schema:givenName Jing-Wen
145 rdf:type schema:Person
146 Nc0304fed66a14f58a99bd304d1cae6f1 schema:name nlm_unique_id
147 schema:value 101719179
148 rdf:type schema:PropertyValue
149 Nd2e8b406c69143bd9064c46cc5f055a5 schema:name doi
150 schema:value 10.1038/s42003-019-0343-4
151 rdf:type schema:PropertyValue
152 Nd9716eb8d1b542459dea1b2b59e3ece9 rdf:first N225632d542714f05953750d3a3e28292
153 rdf:rest N980265e0ba0d47e090f465db03a9537b
154 Ndfd8e04b8ee2416a8ba9a5e74765a3b2 rdf:first N1fc6bb5ab99e4e2f926d3a1fb9520bfd
155 rdf:rest Nf8bc45b9d5964538a77c9a7698c2273d
156 Ne2c82db1f5324a04a5e43656fd1e3398 schema:volumeNumber 2
157 rdf:type schema:PublicationVolume
158 Ne5a594af7b894bffa0864a132633f136 schema:name Springer Nature - SN SciGraph project
159 rdf:type schema:Organization
160 Nf11d967cefe14e98847da656450d943e schema:name pubmed_id
161 schema:value 30911680
162 rdf:type schema:PropertyValue
163 Nf26f36e90bfb471880bcd2eee6b586aa rdf:first N6a47c731cba54866ba11d4ab1c133a66
164 rdf:rest N3030eff55001419abb33fd2189a01dcf
165 Nf59c5d17310e49f2adf18aecc2c6de51 schema:name readcube_id
166 schema:value 1a84f7b75f2e64f93b96f4610b6c2cb835286e626039d43cb7b9c25a5f97f0fe
167 rdf:type schema:PropertyValue
168 Nf8bc45b9d5964538a77c9a7698c2273d rdf:first N3bf739a490f34766904a9429a46406b4
169 rdf:rest N5722525913924f7caac399e2f2f369b7
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)


...