WIP1 phosphatase modulates the Hedgehog signaling by enhancing GLI1 function View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-10

AUTHORS

S Pandolfi, V Montagnani, J Y Penachioni, M C Vinci, B Olivito, L Borgognoni, B Stecca

ABSTRACT

The Hedgehog-GLI (HH-GLI) signaling plays a critical role in controlling growth and tissue patterning during embryogenesis and is implicated in a variety of human malignancies, including those of the skin. Phosphorylation events have been shown to regulate the activity of the GLI transcription factors, the final effectors of the HH-GLI signaling pathway. Here, we show that WIP1 (or PPM1D), an oncogenic phosphatase amplified/overexpressed in several types of human cancer, is a positive modulator of the HH signaling. Mechanistically, WIP1 enhances the function of GLI1 by increasing its transcriptional activity, nuclear localization and protein stability, but not of GLI2 nor GLI3. We also find that WIP1 and GLI1 are in a complex. Modulation of the transcriptional activity of GLI1 by WIP1 depends on the latter's phosphatase activity and, remarkably, does not require p53, a known WIP1 target. Functionally, we find that WIP1 is required for melanoma and breast cancer cell proliferation and self-renewal in vitro and melanoma xenograft growth induced by activation of the HH signaling. Pharmacological blockade of the HH pathway with the SMOOTHENED antagonist cyclopamine acts synergistically with inhibition of WIP1 in reducing growth of melanoma and breast cancer cells in vitro. Overall, our data uncover a role for WIP1 in modulating the activity of GLI1 and in sustaining cancer cell growth and cancer stem cell self-renewal induced by activation of the HH pathway. These findings open a novel therapeutic approach for human melanomas and, possibly, other cancer types expressing WIP1 and with activated HH pathway. More... »

PAGES

4737

References to SciGraph publications

  • 1998-01. Activating Smoothened mutations in sporadic basal-cell carcinoma in NATURE
  • 2007-09. Patching the gaps in Hedgehog signalling in NATURE CELL BIOLOGY
  • 2006-07. Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1 phosphatase in CELL DEATH & DIFFERENTIATION
  • 2011-07. The Hedgehog's tale: developing strategies for targeting cancer in NATURE REVIEWS CANCER
  • 2003-01. Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo in NATURE NEUROSCIENCE
  • 2008-02. Medulloblastomas overexpress the p53-inactivating oncogene WIP1/PPM1D in JOURNAL OF NEURO-ONCOLOGY
  • 2008-02. A chemical inhibitor of PPM1D that selectively kills cells overexpressing PPM1D in ONCOGENE
  • 2007-02. Melanoma biology and new targeted therapy in NATURE
  • 2000-08. Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine in NATURE
  • 2002-06. Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity in NATURE GENETICS
  • 2007-04. The role of the MKK6/p38 MAPK pathway in Wip1-dependent regulation of ErbB2-driven mammary gland tumorigenesis in ONCOGENE
  • 1999-09. Mammalian Suppressor-of-Fused modulates nuclear–cytoplasmic shuttling of GLI-1 in NATURE CELL BIOLOGY
  • 2005-10. Vertebrate Smoothened functions at the primary cilium in NATURE
  • 2008-06. The type 2C phosphatase Wip1: An oncogenic regulator of tumor suppressor and DNA damage response pathways in CANCER AND METASTASIS REVIEWS
  • 2004-11. Tissue repair and stem cell renewal in carcinogenesis in NATURE
  • 2002-06. Oncogenic properties of PPM1D located within a breast cancer amplification epicenter at 17q23 in NATURE GENETICS
  • 2004-04. Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK–mediated activation of the p16Ink4a-p19Arf pathway in NATURE GENETICS
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/onc.2012.502

    DOI

    http://dx.doi.org/10.1038/onc.2012.502

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1006878030

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23146903


    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/2008/1112", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Oncology and Carcinogenesis", 
            "type": "DefinedTerm"
          }, 
          {
            "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"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Nucleus", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Hedgehog Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Neoplasms", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Neoplastic Stem Cells", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Phosphoprotein Phosphatases", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Protein Binding", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Protein Phosphatase 2C", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Signal Transduction", 
            "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": "Zinc Finger Protein GLI1", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "name": [
                "Laboratory of Tumor Cell Biology, Core Research Laboratory\u2014Istituto Toscano Tumori (CRL-ITT), Florence, Italy"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Pandolfi", 
            "givenName": "S", 
            "id": "sg:person.01107242747.39", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01107242747.39"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "name": [
                "Laboratory of Tumor Cell Biology, Core Research Laboratory\u2014Istituto Toscano Tumori (CRL-ITT), Florence, Italy"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Montagnani", 
            "givenName": "V", 
            "id": "sg:person.01223471347.66", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01223471347.66"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "name": [
                "Laboratory of Tumor Cell Biology, Core Research Laboratory\u2014Istituto Toscano Tumori (CRL-ITT), Florence, Italy"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Penachioni", 
            "givenName": "J Y", 
            "id": "sg:person.01155356147.74", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01155356147.74"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "name": [
                "Laboratory of Tumor Cell Biology, Core Research Laboratory\u2014Istituto Toscano Tumori (CRL-ITT), Florence, Italy"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Vinci", 
            "givenName": "M C", 
            "id": "sg:person.01041127547.32", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01041127547.32"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Meyer Children's Hospital", 
              "id": "https://www.grid.ac/institutes/grid.413181.e", 
              "name": [
                "Department of Pediatrics, Immunology Unit, Anna Meyer Children's Hospital, Florence, Italy"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Olivito", 
            "givenName": "B", 
            "id": "sg:person.0650256776.49", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0650256776.49"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Azienda Ospedaliero-Universitaria Careggi", 
              "id": "https://www.grid.ac/institutes/grid.24704.35", 
              "name": [
                "Plastic Surgery Unit, S.M. Annunziata Hospital\u2014Regional Melanoma Referral Center, Istituto Toscano Tumori, Florence, Italy"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Borgognoni", 
            "givenName": "L", 
            "id": "sg:person.0653251344.12", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0653251344.12"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "name": [
                "Laboratory of Tumor Cell Biology, Core Research Laboratory\u2014Istituto Toscano Tumori (CRL-ITT), Florence, Italy"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Stecca", 
            "givenName": "B", 
            "id": "sg:person.01220200153.86", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01220200153.86"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1007/s11060-007-9470-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1000050733", 
              "https://doi.org/10.1007/s11060-007-9470-8"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.ccr.2011.12.028", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1000928307"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.devcel.2008.11.010", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001101100"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.devcel.2008.11.010", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001101100"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1227/neu.0b013e31823e5332", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001172640"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.0700776104", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001727977"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrc3079", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002860275", 
              "https://doi.org/10.1038/nrc3079"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/35023008", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003045945", 
              "https://doi.org/10.1038/35023008"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/35023008", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003045945", 
              "https://doi.org/10.1038/35023008"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1128/mcb.02317-05", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003991793"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1101/gad.1061803", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004107821"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/jmcb/mjp052", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004363882"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/jmcb/mjp052", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004363882"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/0008-5472.can-06-0054", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005048421"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/0008-5472.can-07-6174", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005249976"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cancergencyto.2007.12.013", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006856620"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nn983", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1007662899", 
              "https://doi.org/10.1038/nn983"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nn983", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1007662899", 
              "https://doi.org/10.1038/nn983"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.0611682104", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1007995605"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/mc.20195", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010842430"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature03100", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1011023571", 
              "https://doi.org/10.1038/nature03100"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature03100", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1011023571", 
              "https://doi.org/10.1038/nature03100"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/bi101949t", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1011729168"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/bi101949t", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1011729168"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.ydbio.2006.10.011", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012633825"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.0712216105", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012786624"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1242/dev.030015", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015255923"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1101/gad.938601", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015425762"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1101/gad.1753809", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018069085"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature05661", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021487923", 
              "https://doi.org/10.1038/nature05661"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/emmm.200900039", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022456094"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/34201", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022953597", 
              "https://doi.org/10.1038/34201"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/34201", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022953597", 
              "https://doi.org/10.1038/34201"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1101/gad.1380906", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1028156058"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/emmm.201100201", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1028347208"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.brainres.2011.12.052", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1028406832"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cub.2006.11.033", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029135252"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.1139740", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029274569"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1101/gad.1437206", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029358944"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1200/jco.2010.27.9943", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029942427"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.molcel.2006.07.010", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030200283"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1210032", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030402310", 
              "https://doi.org/10.1038/sj.onc.1210032"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1210032", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030402310", 
              "https://doi.org/10.1038/sj.onc.1210032"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10555-008-9127-x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030791778", 
              "https://doi.org/10.1007/s10555-008-9127-x"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10555-008-9127-x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030791778", 
              "https://doi.org/10.1007/s10555-008-9127-x"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.94.12.6048", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032354117"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/stem.65", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032781158"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/stem.65", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032781158"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.m601758200", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033119522"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.ccr.2007.08.033", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033137558"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1101/gad.1693608", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033537582"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.182542899", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034974301"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/ijc.2910550407", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1035905500"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/0008-5472.can-09-4244", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036413567"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng1317", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037400245", 
              "https://doi.org/10.1038/ng1317"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng1317", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037400245", 
              "https://doi.org/10.1038/ng1317"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.bbcan.2010.01.003", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037485361"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/0008-5472.can-07-0491", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038202417"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0092-8674(93)90500-p", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038576682"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.cdd.4401801", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038926591", 
              "https://doi.org/10.1038/sj.cdd.4401801"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.cdd.4401801", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038926591", 
              "https://doi.org/10.1038/sj.cdd.4401801"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.stem.2007.05.020", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039761776"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cmet.2012.06.003", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1040134270"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/stem.1160", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041362468"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1371/journal.pone.0007471", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041891741"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng888", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042169059", 
              "https://doi.org/10.1038/ng888"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng888", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042169059", 
              "https://doi.org/10.1038/ng888"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.m109.021949", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042367668"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncb435", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1043349302", 
              "https://doi.org/10.1038/ncb435"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.m608599200", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044708964"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1101/gad.1291305", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046561662"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/emboj/19.23.6517", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1047464723"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0092-8674(00)81268-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1047995155"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/hmg/ddi222", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1047998044"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature04117", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048565750", 
              "https://doi.org/10.1038/nature04117"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature04117", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048565750", 
              "https://doi.org/10.1038/nature04117"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature04117", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048565750", 
              "https://doi.org/10.1038/nature04117"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1038/emboj.2009.246", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048721306"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1038/emboj.2009.246", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048721306"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.m111.274761", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049601653"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1128/mcb.22.4.1094-1105.2002", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050246923"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/0008-5472.can-10-0697", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050300588"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng894", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050874862", 
              "https://doi.org/10.1038/ng894"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng894", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050874862", 
              "https://doi.org/10.1038/ng894"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1210729", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051124980", 
              "https://doi.org/10.1038/sj.onc.1210729"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1038/emboj.2009.16", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051239273"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/13031", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1052443268", 
              "https://doi.org/10.1038/13031"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/13031", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1052443268", 
              "https://doi.org/10.1038/13031"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0006-3495(04)74328-3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053078958"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/bi061356b", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1055202415"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/bi061356b", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1055202415"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.272.5268.1668", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062553319"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1075298786", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1083077447", 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2013-10", 
        "datePublishedReg": "2013-10-01", 
        "description": "The Hedgehog-GLI (HH-GLI) signaling plays a critical role in controlling growth and tissue patterning during embryogenesis and is implicated in a variety of human malignancies, including those of the skin. Phosphorylation events have been shown to regulate the activity of the GLI transcription factors, the final effectors of the HH-GLI signaling pathway. Here, we show that WIP1 (or PPM1D), an oncogenic phosphatase amplified/overexpressed in several types of human cancer, is a positive modulator of the HH signaling. Mechanistically, WIP1 enhances the function of GLI1 by increasing its transcriptional activity, nuclear localization and protein stability, but not of GLI2 nor GLI3. We also find that WIP1 and GLI1 are in a complex. Modulation of the transcriptional activity of GLI1 by WIP1 depends on the latter's phosphatase activity and, remarkably, does not require p53, a known WIP1 target. Functionally, we find that WIP1 is required for melanoma and breast cancer cell proliferation and self-renewal in vitro and melanoma xenograft growth induced by activation of the HH signaling. Pharmacological blockade of the HH pathway with the SMOOTHENED antagonist cyclopamine acts synergistically with inhibition of WIP1 in reducing growth of melanoma and breast cancer cells in vitro. Overall, our data uncover a role for WIP1 in modulating the activity of GLI1 and in sustaining cancer cell growth and cancer stem cell self-renewal induced by activation of the HH pathway. These findings open a novel therapeutic approach for human melanomas and, possibly, other cancer types expressing WIP1 and with activated HH pathway. ", 
        "genre": "research_article", 
        "id": "sg:pub.10.1038/onc.2012.502", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": true, 
        "isPartOf": [
          {
            "id": "sg:journal.1097543", 
            "issn": [
              "0950-9232", 
              "1476-5594"
            ], 
            "name": "Oncogene", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "40", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "32"
          }
        ], 
        "name": "WIP1 phosphatase modulates the Hedgehog signaling by enhancing GLI1 function", 
        "pagination": "4737", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "20c34dbf2ae47a51b739fa04d7aa541d70cdb0f38c531341fa625c81a80dd16f"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "23146903"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "8711562"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/onc.2012.502"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1006878030"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/onc.2012.502", 
          "https://app.dimensions.ai/details/publication/pub.1006878030"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-10T21:26", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8687_00000438.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://www.nature.com/articles/onc2012502"
      }
    ]
     

    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.2012.502'

    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.2012.502'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/onc.2012.502'

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

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/onc.2012.502'


     

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

    412 TRIPLES      21 PREDICATES      116 URIs      33 LITERALS      21 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/onc.2012.502 schema:about N0041557d761e46d2a4ceb634029aa516
    2 N155edca333df4442a56e6d3d890f3c0a
    3 N1f4f82f54a184ee68872bce31d70ff70
    4 N2a89ba3777f14dc280c170cf2b429f6e
    5 N4f49d59d521b4b759d190b2e6780ab2f
    6 N58b163bf73b34198adcd30dd0bfa5d03
    7 N5d581096fcdf417e812c13ee2c17fac7
    8 N6b1d7ff829fb4094b91d847c19082b63
    9 N80af56323c5d4f45844632db5006ef25
    10 N939fe1b1a50841b688c71275d5e764f0
    11 Ncdd431b5394a4ed9ae7cb153a497d7fb
    12 Ned3ef534f4ae45b98dd0aeaff2a35f07
    13 anzsrc-for:11
    14 anzsrc-for:1112
    15 schema:author N4ae910c6ebe24a1eb67d280cc5629164
    16 schema:citation sg:pub.10.1007/s10555-008-9127-x
    17 sg:pub.10.1007/s11060-007-9470-8
    18 sg:pub.10.1038/13031
    19 sg:pub.10.1038/34201
    20 sg:pub.10.1038/35023008
    21 sg:pub.10.1038/nature03100
    22 sg:pub.10.1038/nature04117
    23 sg:pub.10.1038/nature05661
    24 sg:pub.10.1038/ncb435
    25 sg:pub.10.1038/ng1317
    26 sg:pub.10.1038/ng888
    27 sg:pub.10.1038/ng894
    28 sg:pub.10.1038/nn983
    29 sg:pub.10.1038/nrc3079
    30 sg:pub.10.1038/sj.cdd.4401801
    31 sg:pub.10.1038/sj.onc.1210032
    32 sg:pub.10.1038/sj.onc.1210729
    33 https://app.dimensions.ai/details/publication/pub.1075298786
    34 https://app.dimensions.ai/details/publication/pub.1083077447
    35 https://doi.org/10.1002/emmm.200900039
    36 https://doi.org/10.1002/emmm.201100201
    37 https://doi.org/10.1002/ijc.2910550407
    38 https://doi.org/10.1002/mc.20195
    39 https://doi.org/10.1002/stem.1160
    40 https://doi.org/10.1002/stem.65
    41 https://doi.org/10.1016/0092-8674(93)90500-p
    42 https://doi.org/10.1016/j.bbcan.2010.01.003
    43 https://doi.org/10.1016/j.brainres.2011.12.052
    44 https://doi.org/10.1016/j.cancergencyto.2007.12.013
    45 https://doi.org/10.1016/j.ccr.2007.08.033
    46 https://doi.org/10.1016/j.ccr.2011.12.028
    47 https://doi.org/10.1016/j.cmet.2012.06.003
    48 https://doi.org/10.1016/j.cub.2006.11.033
    49 https://doi.org/10.1016/j.devcel.2008.11.010
    50 https://doi.org/10.1016/j.molcel.2006.07.010
    51 https://doi.org/10.1016/j.stem.2007.05.020
    52 https://doi.org/10.1016/j.ydbio.2006.10.011
    53 https://doi.org/10.1016/s0006-3495(04)74328-3
    54 https://doi.org/10.1016/s0092-8674(00)81268-4
    55 https://doi.org/10.1021/bi061356b
    56 https://doi.org/10.1021/bi101949t
    57 https://doi.org/10.1038/emboj.2009.16
    58 https://doi.org/10.1038/emboj.2009.246
    59 https://doi.org/10.1073/pnas.0611682104
    60 https://doi.org/10.1073/pnas.0700776104
    61 https://doi.org/10.1073/pnas.0712216105
    62 https://doi.org/10.1073/pnas.182542899
    63 https://doi.org/10.1073/pnas.94.12.6048
    64 https://doi.org/10.1074/jbc.m109.021949
    65 https://doi.org/10.1074/jbc.m111.274761
    66 https://doi.org/10.1074/jbc.m601758200
    67 https://doi.org/10.1074/jbc.m608599200
    68 https://doi.org/10.1093/emboj/19.23.6517
    69 https://doi.org/10.1093/hmg/ddi222
    70 https://doi.org/10.1093/jmcb/mjp052
    71 https://doi.org/10.1101/gad.1061803
    72 https://doi.org/10.1101/gad.1291305
    73 https://doi.org/10.1101/gad.1380906
    74 https://doi.org/10.1101/gad.1437206
    75 https://doi.org/10.1101/gad.1693608
    76 https://doi.org/10.1101/gad.1753809
    77 https://doi.org/10.1101/gad.938601
    78 https://doi.org/10.1126/science.1139740
    79 https://doi.org/10.1126/science.272.5268.1668
    80 https://doi.org/10.1128/mcb.02317-05
    81 https://doi.org/10.1128/mcb.22.4.1094-1105.2002
    82 https://doi.org/10.1158/0008-5472.can-06-0054
    83 https://doi.org/10.1158/0008-5472.can-07-0491
    84 https://doi.org/10.1158/0008-5472.can-07-6174
    85 https://doi.org/10.1158/0008-5472.can-09-4244
    86 https://doi.org/10.1158/0008-5472.can-10-0697
    87 https://doi.org/10.1200/jco.2010.27.9943
    88 https://doi.org/10.1227/neu.0b013e31823e5332
    89 https://doi.org/10.1242/dev.030015
    90 https://doi.org/10.1371/journal.pone.0007471
    91 schema:datePublished 2013-10
    92 schema:datePublishedReg 2013-10-01
    93 schema:description The Hedgehog-GLI (HH-GLI) signaling plays a critical role in controlling growth and tissue patterning during embryogenesis and is implicated in a variety of human malignancies, including those of the skin. Phosphorylation events have been shown to regulate the activity of the GLI transcription factors, the final effectors of the HH-GLI signaling pathway. Here, we show that WIP1 (or PPM1D), an oncogenic phosphatase amplified/overexpressed in several types of human cancer, is a positive modulator of the HH signaling. Mechanistically, WIP1 enhances the function of GLI1 by increasing its transcriptional activity, nuclear localization and protein stability, but not of GLI2 nor GLI3. We also find that WIP1 and GLI1 are in a complex. Modulation of the transcriptional activity of GLI1 by WIP1 depends on the latter's phosphatase activity and, remarkably, does not require p53, a known WIP1 target. Functionally, we find that WIP1 is required for melanoma and breast cancer cell proliferation and self-renewal in vitro and melanoma xenograft growth induced by activation of the HH signaling. Pharmacological blockade of the HH pathway with the SMOOTHENED antagonist cyclopamine acts synergistically with inhibition of WIP1 in reducing growth of melanoma and breast cancer cells in vitro. Overall, our data uncover a role for WIP1 in modulating the activity of GLI1 and in sustaining cancer cell growth and cancer stem cell self-renewal induced by activation of the HH pathway. These findings open a novel therapeutic approach for human melanomas and, possibly, other cancer types expressing WIP1 and with activated HH pathway.
    94 schema:genre research_article
    95 schema:inLanguage en
    96 schema:isAccessibleForFree true
    97 schema:isPartOf N23621a0855d8401ab39742b9a8eb6095
    98 Nf0841e524c2a465dbf186b6ed7cb36c2
    99 sg:journal.1097543
    100 schema:name WIP1 phosphatase modulates the Hedgehog signaling by enhancing GLI1 function
    101 schema:pagination 4737
    102 schema:productId N260978e60b85475cb1885a54097c9887
    103 N53d54c5ebe8b4eddbabf07defeeb5c69
    104 N7f3e7e1d12c448e889e0298ac0e78764
    105 Nc299653853c04603b5875445aedd4e76
    106 Nf914f9a0632544d0ba4bc7de6d80fe1b
    107 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006878030
    108 https://doi.org/10.1038/onc.2012.502
    109 schema:sdDatePublished 2019-04-10T21:26
    110 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    111 schema:sdPublisher Nf3e65aee2cb24deb8e5ee660fbce6367
    112 schema:url https://www.nature.com/articles/onc2012502
    113 sgo:license sg:explorer/license/
    114 sgo:sdDataset articles
    115 rdf:type schema:ScholarlyArticle
    116 N0041557d761e46d2a4ceb634029aa516 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    117 schema:name Neoplastic Stem Cells
    118 rdf:type schema:DefinedTerm
    119 N052281260a0344329011ed277e2070d9 schema:name Laboratory of Tumor Cell Biology, Core Research Laboratory—Istituto Toscano Tumori (CRL-ITT), Florence, Italy
    120 rdf:type schema:Organization
    121 N09fe0a575b2146c191d7cf96efecc9ef schema:name Laboratory of Tumor Cell Biology, Core Research Laboratory—Istituto Toscano Tumori (CRL-ITT), Florence, Italy
    122 rdf:type schema:Organization
    123 N155edca333df4442a56e6d3d890f3c0a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    124 schema:name Hedgehog Proteins
    125 rdf:type schema:DefinedTerm
    126 N1c703757b6684a11a5d5dd3f090a3dc0 schema:name Laboratory of Tumor Cell Biology, Core Research Laboratory—Istituto Toscano Tumori (CRL-ITT), Florence, Italy
    127 rdf:type schema:Organization
    128 N1f4f82f54a184ee68872bce31d70ff70 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    129 schema:name Humans
    130 rdf:type schema:DefinedTerm
    131 N21a1c6a3baa94c0ea2709c0218700184 schema:name Laboratory of Tumor Cell Biology, Core Research Laboratory—Istituto Toscano Tumori (CRL-ITT), Florence, Italy
    132 rdf:type schema:Organization
    133 N23621a0855d8401ab39742b9a8eb6095 schema:issueNumber 40
    134 rdf:type schema:PublicationIssue
    135 N23cd618788d448eebe86f9aae3b0c2f2 rdf:first sg:person.01220200153.86
    136 rdf:rest rdf:nil
    137 N260978e60b85475cb1885a54097c9887 schema:name doi
    138 schema:value 10.1038/onc.2012.502
    139 rdf:type schema:PropertyValue
    140 N2a89ba3777f14dc280c170cf2b429f6e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    141 schema:name Zinc Finger Protein GLI1
    142 rdf:type schema:DefinedTerm
    143 N4ae910c6ebe24a1eb67d280cc5629164 rdf:first sg:person.01107242747.39
    144 rdf:rest Na5cee1a7a4014538b5928bf6fdf894e2
    145 N4f49d59d521b4b759d190b2e6780ab2f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    146 schema:name Protein Phosphatase 2C
    147 rdf:type schema:DefinedTerm
    148 N53768a2536be45fcaf99e85314382b57 rdf:first sg:person.0650256776.49
    149 rdf:rest N56594345a9e54f0190af304ee189197d
    150 N53d54c5ebe8b4eddbabf07defeeb5c69 schema:name dimensions_id
    151 schema:value pub.1006878030
    152 rdf:type schema:PropertyValue
    153 N56594345a9e54f0190af304ee189197d rdf:first sg:person.0653251344.12
    154 rdf:rest N23cd618788d448eebe86f9aae3b0c2f2
    155 N58b163bf73b34198adcd30dd0bfa5d03 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    156 schema:name Neoplasms
    157 rdf:type schema:DefinedTerm
    158 N5d581096fcdf417e812c13ee2c17fac7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    159 schema:name Protein Binding
    160 rdf:type schema:DefinedTerm
    161 N6b1d7ff829fb4094b91d847c19082b63 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    162 schema:name Transcription Factors
    163 rdf:type schema:DefinedTerm
    164 N7f3e7e1d12c448e889e0298ac0e78764 schema:name readcube_id
    165 schema:value 20c34dbf2ae47a51b739fa04d7aa541d70cdb0f38c531341fa625c81a80dd16f
    166 rdf:type schema:PropertyValue
    167 N80af56323c5d4f45844632db5006ef25 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    168 schema:name Phosphoprotein Phosphatases
    169 rdf:type schema:DefinedTerm
    170 N8bc3e169bcac4df6b4d380193c5b6a38 schema:name Laboratory of Tumor Cell Biology, Core Research Laboratory—Istituto Toscano Tumori (CRL-ITT), Florence, Italy
    171 rdf:type schema:Organization
    172 N939fe1b1a50841b688c71275d5e764f0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    173 schema:name Cell Nucleus
    174 rdf:type schema:DefinedTerm
    175 N981dd219b4754fa89f0ea21300c144db rdf:first sg:person.01041127547.32
    176 rdf:rest N53768a2536be45fcaf99e85314382b57
    177 Na5448c0affd84768a3249e1ee9f885b7 rdf:first sg:person.01155356147.74
    178 rdf:rest N981dd219b4754fa89f0ea21300c144db
    179 Na5cee1a7a4014538b5928bf6fdf894e2 rdf:first sg:person.01223471347.66
    180 rdf:rest Na5448c0affd84768a3249e1ee9f885b7
    181 Nc299653853c04603b5875445aedd4e76 schema:name pubmed_id
    182 schema:value 23146903
    183 rdf:type schema:PropertyValue
    184 Ncdd431b5394a4ed9ae7cb153a497d7fb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    185 schema:name Signal Transduction
    186 rdf:type schema:DefinedTerm
    187 Ned3ef534f4ae45b98dd0aeaff2a35f07 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    188 schema:name Transcription, Genetic
    189 rdf:type schema:DefinedTerm
    190 Nf0841e524c2a465dbf186b6ed7cb36c2 schema:volumeNumber 32
    191 rdf:type schema:PublicationVolume
    192 Nf3e65aee2cb24deb8e5ee660fbce6367 schema:name Springer Nature - SN SciGraph project
    193 rdf:type schema:Organization
    194 Nf914f9a0632544d0ba4bc7de6d80fe1b schema:name nlm_unique_id
    195 schema:value 8711562
    196 rdf:type schema:PropertyValue
    197 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    198 schema:name Medical and Health Sciences
    199 rdf:type schema:DefinedTerm
    200 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
    201 schema:name Oncology and Carcinogenesis
    202 rdf:type schema:DefinedTerm
    203 sg:journal.1097543 schema:issn 0950-9232
    204 1476-5594
    205 schema:name Oncogene
    206 rdf:type schema:Periodical
    207 sg:person.01041127547.32 schema:affiliation N21a1c6a3baa94c0ea2709c0218700184
    208 schema:familyName Vinci
    209 schema:givenName M C
    210 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01041127547.32
    211 rdf:type schema:Person
    212 sg:person.01107242747.39 schema:affiliation N1c703757b6684a11a5d5dd3f090a3dc0
    213 schema:familyName Pandolfi
    214 schema:givenName S
    215 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01107242747.39
    216 rdf:type schema:Person
    217 sg:person.01155356147.74 schema:affiliation N052281260a0344329011ed277e2070d9
    218 schema:familyName Penachioni
    219 schema:givenName J Y
    220 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01155356147.74
    221 rdf:type schema:Person
    222 sg:person.01220200153.86 schema:affiliation N09fe0a575b2146c191d7cf96efecc9ef
    223 schema:familyName Stecca
    224 schema:givenName B
    225 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01220200153.86
    226 rdf:type schema:Person
    227 sg:person.01223471347.66 schema:affiliation N8bc3e169bcac4df6b4d380193c5b6a38
    228 schema:familyName Montagnani
    229 schema:givenName V
    230 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01223471347.66
    231 rdf:type schema:Person
    232 sg:person.0650256776.49 schema:affiliation https://www.grid.ac/institutes/grid.413181.e
    233 schema:familyName Olivito
    234 schema:givenName B
    235 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0650256776.49
    236 rdf:type schema:Person
    237 sg:person.0653251344.12 schema:affiliation https://www.grid.ac/institutes/grid.24704.35
    238 schema:familyName Borgognoni
    239 schema:givenName L
    240 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0653251344.12
    241 rdf:type schema:Person
    242 sg:pub.10.1007/s10555-008-9127-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1030791778
    243 https://doi.org/10.1007/s10555-008-9127-x
    244 rdf:type schema:CreativeWork
    245 sg:pub.10.1007/s11060-007-9470-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000050733
    246 https://doi.org/10.1007/s11060-007-9470-8
    247 rdf:type schema:CreativeWork
    248 sg:pub.10.1038/13031 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052443268
    249 https://doi.org/10.1038/13031
    250 rdf:type schema:CreativeWork
    251 sg:pub.10.1038/34201 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022953597
    252 https://doi.org/10.1038/34201
    253 rdf:type schema:CreativeWork
    254 sg:pub.10.1038/35023008 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003045945
    255 https://doi.org/10.1038/35023008
    256 rdf:type schema:CreativeWork
    257 sg:pub.10.1038/nature03100 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011023571
    258 https://doi.org/10.1038/nature03100
    259 rdf:type schema:CreativeWork
    260 sg:pub.10.1038/nature04117 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048565750
    261 https://doi.org/10.1038/nature04117
    262 rdf:type schema:CreativeWork
    263 sg:pub.10.1038/nature05661 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021487923
    264 https://doi.org/10.1038/nature05661
    265 rdf:type schema:CreativeWork
    266 sg:pub.10.1038/ncb435 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043349302
    267 https://doi.org/10.1038/ncb435
    268 rdf:type schema:CreativeWork
    269 sg:pub.10.1038/ng1317 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037400245
    270 https://doi.org/10.1038/ng1317
    271 rdf:type schema:CreativeWork
    272 sg:pub.10.1038/ng888 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042169059
    273 https://doi.org/10.1038/ng888
    274 rdf:type schema:CreativeWork
    275 sg:pub.10.1038/ng894 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050874862
    276 https://doi.org/10.1038/ng894
    277 rdf:type schema:CreativeWork
    278 sg:pub.10.1038/nn983 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007662899
    279 https://doi.org/10.1038/nn983
    280 rdf:type schema:CreativeWork
    281 sg:pub.10.1038/nrc3079 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002860275
    282 https://doi.org/10.1038/nrc3079
    283 rdf:type schema:CreativeWork
    284 sg:pub.10.1038/sj.cdd.4401801 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038926591
    285 https://doi.org/10.1038/sj.cdd.4401801
    286 rdf:type schema:CreativeWork
    287 sg:pub.10.1038/sj.onc.1210032 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030402310
    288 https://doi.org/10.1038/sj.onc.1210032
    289 rdf:type schema:CreativeWork
    290 sg:pub.10.1038/sj.onc.1210729 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051124980
    291 https://doi.org/10.1038/sj.onc.1210729
    292 rdf:type schema:CreativeWork
    293 https://app.dimensions.ai/details/publication/pub.1075298786 schema:CreativeWork
    294 https://app.dimensions.ai/details/publication/pub.1083077447 schema:CreativeWork
    295 https://doi.org/10.1002/emmm.200900039 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022456094
    296 rdf:type schema:CreativeWork
    297 https://doi.org/10.1002/emmm.201100201 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028347208
    298 rdf:type schema:CreativeWork
    299 https://doi.org/10.1002/ijc.2910550407 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035905500
    300 rdf:type schema:CreativeWork
    301 https://doi.org/10.1002/mc.20195 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010842430
    302 rdf:type schema:CreativeWork
    303 https://doi.org/10.1002/stem.1160 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041362468
    304 rdf:type schema:CreativeWork
    305 https://doi.org/10.1002/stem.65 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032781158
    306 rdf:type schema:CreativeWork
    307 https://doi.org/10.1016/0092-8674(93)90500-p schema:sameAs https://app.dimensions.ai/details/publication/pub.1038576682
    308 rdf:type schema:CreativeWork
    309 https://doi.org/10.1016/j.bbcan.2010.01.003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037485361
    310 rdf:type schema:CreativeWork
    311 https://doi.org/10.1016/j.brainres.2011.12.052 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028406832
    312 rdf:type schema:CreativeWork
    313 https://doi.org/10.1016/j.cancergencyto.2007.12.013 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006856620
    314 rdf:type schema:CreativeWork
    315 https://doi.org/10.1016/j.ccr.2007.08.033 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033137558
    316 rdf:type schema:CreativeWork
    317 https://doi.org/10.1016/j.ccr.2011.12.028 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000928307
    318 rdf:type schema:CreativeWork
    319 https://doi.org/10.1016/j.cmet.2012.06.003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040134270
    320 rdf:type schema:CreativeWork
    321 https://doi.org/10.1016/j.cub.2006.11.033 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029135252
    322 rdf:type schema:CreativeWork
    323 https://doi.org/10.1016/j.devcel.2008.11.010 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001101100
    324 rdf:type schema:CreativeWork
    325 https://doi.org/10.1016/j.molcel.2006.07.010 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030200283
    326 rdf:type schema:CreativeWork
    327 https://doi.org/10.1016/j.stem.2007.05.020 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039761776
    328 rdf:type schema:CreativeWork
    329 https://doi.org/10.1016/j.ydbio.2006.10.011 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012633825
    330 rdf:type schema:CreativeWork
    331 https://doi.org/10.1016/s0006-3495(04)74328-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053078958
    332 rdf:type schema:CreativeWork
    333 https://doi.org/10.1016/s0092-8674(00)81268-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047995155
    334 rdf:type schema:CreativeWork
    335 https://doi.org/10.1021/bi061356b schema:sameAs https://app.dimensions.ai/details/publication/pub.1055202415
    336 rdf:type schema:CreativeWork
    337 https://doi.org/10.1021/bi101949t schema:sameAs https://app.dimensions.ai/details/publication/pub.1011729168
    338 rdf:type schema:CreativeWork
    339 https://doi.org/10.1038/emboj.2009.16 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051239273
    340 rdf:type schema:CreativeWork
    341 https://doi.org/10.1038/emboj.2009.246 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048721306
    342 rdf:type schema:CreativeWork
    343 https://doi.org/10.1073/pnas.0611682104 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007995605
    344 rdf:type schema:CreativeWork
    345 https://doi.org/10.1073/pnas.0700776104 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001727977
    346 rdf:type schema:CreativeWork
    347 https://doi.org/10.1073/pnas.0712216105 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012786624
    348 rdf:type schema:CreativeWork
    349 https://doi.org/10.1073/pnas.182542899 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034974301
    350 rdf:type schema:CreativeWork
    351 https://doi.org/10.1073/pnas.94.12.6048 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032354117
    352 rdf:type schema:CreativeWork
    353 https://doi.org/10.1074/jbc.m109.021949 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042367668
    354 rdf:type schema:CreativeWork
    355 https://doi.org/10.1074/jbc.m111.274761 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049601653
    356 rdf:type schema:CreativeWork
    357 https://doi.org/10.1074/jbc.m601758200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033119522
    358 rdf:type schema:CreativeWork
    359 https://doi.org/10.1074/jbc.m608599200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044708964
    360 rdf:type schema:CreativeWork
    361 https://doi.org/10.1093/emboj/19.23.6517 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047464723
    362 rdf:type schema:CreativeWork
    363 https://doi.org/10.1093/hmg/ddi222 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047998044
    364 rdf:type schema:CreativeWork
    365 https://doi.org/10.1093/jmcb/mjp052 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004363882
    366 rdf:type schema:CreativeWork
    367 https://doi.org/10.1101/gad.1061803 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004107821
    368 rdf:type schema:CreativeWork
    369 https://doi.org/10.1101/gad.1291305 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046561662
    370 rdf:type schema:CreativeWork
    371 https://doi.org/10.1101/gad.1380906 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028156058
    372 rdf:type schema:CreativeWork
    373 https://doi.org/10.1101/gad.1437206 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029358944
    374 rdf:type schema:CreativeWork
    375 https://doi.org/10.1101/gad.1693608 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033537582
    376 rdf:type schema:CreativeWork
    377 https://doi.org/10.1101/gad.1753809 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018069085
    378 rdf:type schema:CreativeWork
    379 https://doi.org/10.1101/gad.938601 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015425762
    380 rdf:type schema:CreativeWork
    381 https://doi.org/10.1126/science.1139740 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029274569
    382 rdf:type schema:CreativeWork
    383 https://doi.org/10.1126/science.272.5268.1668 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062553319
    384 rdf:type schema:CreativeWork
    385 https://doi.org/10.1128/mcb.02317-05 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003991793
    386 rdf:type schema:CreativeWork
    387 https://doi.org/10.1128/mcb.22.4.1094-1105.2002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050246923
    388 rdf:type schema:CreativeWork
    389 https://doi.org/10.1158/0008-5472.can-06-0054 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005048421
    390 rdf:type schema:CreativeWork
    391 https://doi.org/10.1158/0008-5472.can-07-0491 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038202417
    392 rdf:type schema:CreativeWork
    393 https://doi.org/10.1158/0008-5472.can-07-6174 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005249976
    394 rdf:type schema:CreativeWork
    395 https://doi.org/10.1158/0008-5472.can-09-4244 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036413567
    396 rdf:type schema:CreativeWork
    397 https://doi.org/10.1158/0008-5472.can-10-0697 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050300588
    398 rdf:type schema:CreativeWork
    399 https://doi.org/10.1200/jco.2010.27.9943 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029942427
    400 rdf:type schema:CreativeWork
    401 https://doi.org/10.1227/neu.0b013e31823e5332 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001172640
    402 rdf:type schema:CreativeWork
    403 https://doi.org/10.1242/dev.030015 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015255923
    404 rdf:type schema:CreativeWork
    405 https://doi.org/10.1371/journal.pone.0007471 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041891741
    406 rdf:type schema:CreativeWork
    407 https://www.grid.ac/institutes/grid.24704.35 schema:alternateName Azienda Ospedaliero-Universitaria Careggi
    408 schema:name Plastic Surgery Unit, S.M. Annunziata Hospital—Regional Melanoma Referral Center, Istituto Toscano Tumori, Florence, Italy
    409 rdf:type schema:Organization
    410 https://www.grid.ac/institutes/grid.413181.e schema:alternateName Meyer Children's Hospital
    411 schema:name Department of Pediatrics, Immunology Unit, Anna Meyer Children's Hospital, Florence, Italy
    412 rdf:type schema:Organization
     




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


    ...