{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360004236366973056.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1158/0008-5472.can-12-0572"}},{"identifier":{"@type":"URI","@value":"https://aacrjournals.org/cancerres/article-pdf/72/11/2901/2668252/2901.pdf"}},{"identifier":{"@type":"PMID","@value":"22593196"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"The RASSF3 Candidate Tumor Suppressor Induces Apoptosis and G1–S Cell-Cycle Arrest via p53"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title>\n                  <jats:p>RASSF3 is the smallest member of the RASSF family of proteins that function as tumor suppressors. Unlike other members of this important family, the mechanisms through which RASSF3 suppresses tumor formation remain unknown. Here, we show that RASSF3 expression induces p53-dependent apoptosis and its depletion attenuates DNA damage–induced apoptosis. We found that RASSF3-induced apoptosis depended upon p53 expression. Exogenous expression of RASSF3 induced G1–S arrest, which was also p53 dependent. In contrast, loss of RASSF3 promoted cell-cycle progression, abrogated UVB- and VP-16–induced G1–S arrest, decreased p53 protein and target gene expression, and prevented DNA repair. RASSF3 was shown to directly interact with and facilitate the ubiquitination of MDM2, the E3 ligase that targets p53 for degradation, thereby increasing p53 stabilization. Together, our findings show the tumor suppressor activity of RASSF3, which occurs through p53 stabilization and regulation of apoptosis and the cell cycle. Cancer Res; 72(11); 2901–11. ©2012 AACR.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380005521387933830","@type":"Researcher","foaf:name":[{"@value":"Takumi Kudo"}],"jpcoar:affiliationName":[{"@value":"Authors' Affiliations: Departments of 1Medical Biochemistry and 2Neurosurgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan; and 3Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, China"},{"@value":"Authors' Affiliations: Departments of 1Medical Biochemistry and 2Neurosurgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan; and 3Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1380005521387933828","@type":"Researcher","foaf:name":[{"@value":"Mitsunobu Ikeda"}],"jpcoar:affiliationName":[{"@value":"Authors' Affiliations: Departments of 1Medical Biochemistry and 2Neurosurgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan; and 3Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1380005521387933831","@type":"Researcher","foaf:name":[{"@value":"Misa Nishikawa"}],"jpcoar:affiliationName":[{"@value":"Authors' Affiliations: Departments of 1Medical Biochemistry and 2Neurosurgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan; and 3Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1380005521387933954","@type":"Researcher","foaf:name":[{"@value":"Zeyu Yang"}],"jpcoar:affiliationName":[{"@value":"Authors' Affiliations: Departments of 1Medical Biochemistry and 2Neurosurgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan; and 3Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, China"},{"@value":"Authors' Affiliations: Departments of 1Medical Biochemistry and 2Neurosurgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan; and 3Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1380005521387933953","@type":"Researcher","foaf:name":[{"@value":"Kikuo Ohno"}],"jpcoar:affiliationName":[{"@value":"Authors' Affiliations: Departments of 1Medical Biochemistry and 2Neurosurgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan; and 3Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1380005521387933952","@type":"Researcher","foaf:name":[{"@value":"Kentaro Nakagawa"}],"jpcoar:affiliationName":[{"@value":"Authors' Affiliations: Departments of 1Medical Biochemistry and 2Neurosurgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan; and 3Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1030003658466173185","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"80313237"},{"@type":"NRID","@value":"1000080313237"},{"@type":"NRID","@value":"9000019140031"},{"@type":"NRID","@value":"9000002735354"},{"@type":"NRID","@value":"9000007158865"},{"@type":"NRID","@value":"9000009097104"},{"@type":"NRID","@value":"9000004109441"},{"@type":"NRID","@value":"9000004682000"},{"@type":"NRID","@value":"9000399001151"},{"@type":"NRID","@value":"9000001901595"},{"@type":"NRID","@value":"9000000558814"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/yutakahata"}],"foaf:name":[{"@value":"Yutaka Hata"}],"jpcoar:affiliationName":[{"@value":"Authors' Affiliations: Departments of 1Medical Biochemistry and 2Neurosurgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan; and 3Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, China"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00085472"},{"@type":"EISSN","@value":"15387445"}],"prism:publicationName":[{"@value":"Cancer Research"}],"dc:publisher":[{"@value":"American Association for Cancer Research (AACR)"}],"prism:publicationDate":"2012-05-31","prism:volume":"72","prism:number":"11","prism:startingPage":"2901","prism:endingPage":"2911"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","url":[{"@id":"https://aacrjournals.org/cancerres/article-pdf/72/11/2901/2668252/2901.pdf"}],"createdAt":"2012-05-17","modifiedAt":"2022-06-17","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=DNA%20Repair","dc:title":"DNA Repair"},{"@id":"https://cir.nii.ac.jp/all?q=Tumor%20Suppressor%20Proteins","dc:title":"Tumor Suppressor Proteins"},{"@id":"https://cir.nii.ac.jp/all?q=Molecular%20Sequence%20Data","dc:title":"Molecular Sequence Data"},{"@id":"https://cir.nii.ac.jp/all?q=G1%20Phase","dc:title":"G1 Phase"},{"@id":"https://cir.nii.ac.jp/all?q=Apoptosis","dc:title":"Apoptosis"},{"@id":"https://cir.nii.ac.jp/all?q=Proto-Oncogene%20Proteins%20c-mdm2","dc:title":"Proto-Oncogene Proteins c-mdm2"},{"@id":"https://cir.nii.ac.jp/all?q=Cell%20Cycle%20Checkpoints","dc:title":"Cell Cycle Checkpoints"},{"@id":"https://cir.nii.ac.jp/all?q=S%20Phase","dc:title":"S Phase"},{"@id":"https://cir.nii.ac.jp/all?q=Polyploidy","dc:title":"Polyploidy"},{"@id":"https://cir.nii.ac.jp/all?q=Cell%20Line,%20Tumor","dc:title":"Cell Line, Tumor"},{"@id":"https://cir.nii.ac.jp/all?q=Humans","dc:title":"Humans"},{"@id":"https://cir.nii.ac.jp/all?q=Amino%20Acid%20Sequence","dc:title":"Amino Acid Sequence"},{"@id":"https://cir.nii.ac.jp/all?q=Tumor%20Suppressor%20Protein%20p53","dc:title":"Tumor Suppressor Protein p53"},{"@id":"https://cir.nii.ac.jp/all?q=Apoptosis%20Regulatory%20Proteins","dc:title":"Apoptosis Regulatory Proteins"},{"@id":"https://cir.nii.ac.jp/all?q=Adaptor%20Proteins,%20Signal%20Transducing","dc:title":"Adaptor Proteins, Signal Transducing"},{"@id":"https://cir.nii.ac.jp/all?q=Monomeric%20GTP-Binding%20Proteins","dc:title":"Monomeric GTP-Binding Proteins"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040000782136242560","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"22790275"},{"@type":"JGN","@value":"JP22790275"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22790275/"}],"notation":[{"@language":"ja","@value":"RASSF6による細胞死誘導機構の解明"}]},{"@id":"https://cir.nii.ac.jp/crid/1040282257100229504","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"22590267"},{"@type":"JGN","@value":"JP22590267"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590267/"}],"notation":[{"@language":"ja","@value":"ヒッポ・パスウエイのオン・オフ機構の解明"},{"@language":"en","@value":"Regulatory mechanism of the tumor suppressive Hippo pathway"}]},{"@id":"https://cir.nii.ac.jp/crid/1040282257161715328","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"23790325"},{"@type":"JGN","@value":"JP23790325"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790325/"}],"notation":[{"@language":"ja","@value":"Ｈｉｐｐｏシグナル伝達系の活性を制御する化合物の探索とその応用"},{"@language":"en","@value":"Chemical compound screening and development for Hippo signaling pathway"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360285710498787584","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"<scp>BCL</scp>‐<scp>XL</scp> binds and antagonizes <scp>RASSF</scp>6 tumor suppressor to suppress p53 expression"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285714455071232","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"RASSF6; the Putative Tumor Suppressor of the RASSF Family"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292617911098624","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Hallmarks of Cancer: The Next Generation"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292619455255040","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"A Role for the RASSF1A Tumor Suppressor in the Regulation of Tubulin Polymerization and Genomic Stability"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567181096026880","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Tumor suppressor C-RASSF proteins"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567183933942144","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"The RASSF6 Tumor Suppressor Protein Regulates Apoptosis and the Cell Cycle via MDM2 Protein and p53 Protein"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574094452219136","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"N-terminal RASSF family"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574094872704128","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Role of the tumor suppressor RASSF2 in regulation of MST1 kinase activity"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574095503712512","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"p53 in health and disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1360588380160137344","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"A\n                    <i>Recql5</i>\n                    mutant facilitates complex CRISPR/Cas9-mediated chromosomal engineering in mouse zygotes"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848657281013888","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"RASSF3 downregulation increases malignant phenotypes of non-small cell lung cancer"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855570843807104","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras"}]},{"@id":"https://cir.nii.ac.jp/crid/1361137045913237504","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"NORE1A Tumor Suppressor Candidate Modulates p21CIP1 via p53"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418518801601024","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Tumour suppression by p53: a role for the DNA damage response?"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418520683237248","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The tumour suppressor RASSF1A promotes MDM2 self‐ubiquitination by disrupting the MDM2–DAXX–HAUSP complex"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418521359161344","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The RASSF1A Tumor Suppressor Activates Bax via MOAP-1"}]},{"@id":"https://cir.nii.ac.jp/crid/1361699993798638080","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Activation of the p53-dependent G1 checkpoint response in mouse embryo fibroblasts depends on the specific DNA damage inducer"}]},{"@id":"https://cir.nii.ac.jp/crid/1361699994144300800","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Rassf Family of Tumor Suppressor Polypeptides"}]},{"@id":"https://cir.nii.ac.jp/crid/1361699995112167936","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Tumor suppressor RASSF1A is a microtubule-binding protein that stabilizes microtubules and induces G2/M arrest"}]},{"@id":"https://cir.nii.ac.jp/crid/1361981468335768576","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The RASSF1A Tumor Suppressor Blocks Cell Cycle Progression and Inhibits Cyclin D1 Accumulation"}]},{"@id":"https://cir.nii.ac.jp/crid/1361981470232822400","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The N-terminal RASSF family: a new group of Ras-association-domaincontaining proteins, with emerging links to cancer formation"}]},{"@id":"https://cir.nii.ac.jp/crid/1361981471043398272","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Identification of a Novel Ras-Regulated Proapoptotic Pathway"}]},{"@id":"https://cir.nii.ac.jp/crid/1362544418822554368","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Specificity of the Methylation-Suppressed A Isoform of Candidate Tumor Suppressor RASSF1 for Microtubule Hyperstabilization Is Determined by Cell Death Inducer C19ORF5"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825894591299328","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"RASSF1A Elicits Apoptosis through an MST2 Pathway Directing Proapoptotic Transcription by the p73 Tumor Suppressor Protein"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825896005075840","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"RASSF3 and NORE1: identification and cloning of two human homologues of the putative tumor suppressor gene RASSF1"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825896305777280","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Threonine 74 of MOB1 is a putative key phosphorylation site by MST2 to form the scaffold to activate nuclear Dbf2-related kinase 1"}]},{"@id":"https://cir.nii.ac.jp/crid/1363107368559020416","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The Causes and Consequences of Polyploidy in Normal Development and Cancer"}]},{"@id":"https://cir.nii.ac.jp/crid/1363107370776351616","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"RASSF2 associates with and stabilizes the proapoptotic kinase MST2"}]},{"@id":"https://cir.nii.ac.jp/crid/1363107370982103808","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Negative Regulation of Tumor Suppressor p53 by MicroRNA miR-504"}]},{"@id":"https://cir.nii.ac.jp/crid/1363388843830562944","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Regulating the p53 pathway: in vitro hypotheses, in vivo veritas"}]},{"@id":"https://cir.nii.ac.jp/crid/1363388845217475328","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The Tumor Suppressor RASSF1A and MAP-1 Link Death Receptor Signaling to Bax Conformational Change and Cell Death"}]},{"@id":"https://cir.nii.ac.jp/crid/1363388846022055168","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"RASSF1A Is Part of a Complex Similar to the Drosophila Hippo/Salvador/Lats Tumor-Suppressor Network"}]},{"@id":"https://cir.nii.ac.jp/crid/1363670318479168128","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"CIN85 Is Localized at Synapses and Forms a Complex with S-SCAM via Dendrin"}]},{"@id":"https://cir.nii.ac.jp/crid/1363951793862669824","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Hippo Pathway–Dependent and –Independent Roles of RASSF6"}]},{"@id":"https://cir.nii.ac.jp/crid/1363951795113352704","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Ras-association domain family protein 6 induces apoptosis via both caspase-dependent and caspase-independent pathways"}]},{"@id":"https://cir.nii.ac.jp/crid/1364233268351773696","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The tumour suppressor RASSF1A regulates mitosis by inhibiting the APC–Cdc20 complex"}]},{"@id":"https://cir.nii.ac.jp/crid/1370005521387933833","@type":"Product","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Rassf3 is responsible in part for resistance to mammary tumor development in neu transgenic mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1370005521387933962","@type":"Product","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Cellular UV damage responses–functions of tumor suppressor p53"}]},{"@id":"https://cir.nii.ac.jp/crid/1370576195489134720","@type":"Product","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"UV irradiation stimulates levels of p53 cellular tumor antigen in nontransformed mouse cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1370576195489134721","@type":"Product","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The RASSF proteins in cancer; from epigenetic silencing to functional characterization"}]},{"@id":"https://cir.nii.ac.jp/crid/1370576195489134722","@type":"Product","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Cloning and expression of the cDNA for E6-AP, a protein that mediates the interaction of the human papillomavirus E6 oncoprotein with p53"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1158/0008-5472.can-12-0572"},{"@type":"KAKEN","@value":"PRODUCT-13715459"},{"@type":"KAKEN","@value":"PRODUCT-13526203"},{"@type":"KAKEN","@value":"PRODUCT-14407713"},{"@type":"OPENAIRE","@value":"doi_dedup___::4bd04ddd288b7afb41f30cda033ed4b8"},{"@type":"CROSSREF","@value":"10.1016/j.lungcan.2013.10.014_references_DOI_FOXsgYBKLSqTgUf1uw2k3pkXB4m"},{"@type":"CROSSREF","@value":"10.1111/gtc.12541_references_DOI_FOXsgYBKLSqTgUf1uw2k3pkXB4m"},{"@type":"CROSSREF","@value":"10.3390/cancers7040899_references_DOI_FOXsgYBKLSqTgUf1uw2k3pkXB4m"},{"@type":"CROSSREF","@value":"10.1007/s00018-018-2756-5_references_DOI_FOXsgYBKLSqTgUf1uw2k3pkXB4m"},{"@type":"CROSSREF","@value":"10.1074/jbc.m113.507384_references_DOI_FOXsgYBKLSqTgUf1uw2k3pkXB4m"},{"@type":"CROSSREF","@value":"10.1093/genetics/iyae054_references_DOI_FOXsgYBKLSqTgUf1uw2k3pkXB4m"}]}