{"@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/1363670320763800448.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1073/pnas.2627984100"}},{"identifier":{"@type":"URI","@value":"https://pnas.org/doi/pdf/10.1073/pnas.2627984100"}},{"identifier":{"@type":"NAID","@value":"80015837586"}}],"dc:title":[{"@value":"<i>PUMA</i>\n                    mediates the apoptotic response to p53 in colorectal cancer cells"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>\n                    Although several genes that might mediate p53-induced apoptosis have been proposed, none have previously been shown to play an essential role in this process through a rigorous gene disruption approach. We used a gene-targeting approach to evaluate p53-mediated death in human colorectal cancer cells. Expression of p53 in these cells induces growth arrest through transcriptional activation of the cyclin-dependent kinase inhibitor\n                    <jats:italic>p21</jats:italic>\n                    . If\n                    <jats:italic>p21</jats:italic>\n                    is disrupted via gene targeting, the cells die through apoptosis. If the\n                    <jats:italic>PUMA</jats:italic>\n                    gene is also disrupted in such cells, apoptosis is prevented. The effects of PUMA on apoptosis were observed after exogenous overexpression of p53 as well as after exposure to hypoxia, a physiologic activator of p53, and DNA damage. The PUMA protein interacts with Bcl-X\n                    <jats:sub>L</jats:sub>\n                    and promotes mitochondrial translocation and multimerization of Bax. Accordingly, genetic disruption of\n                    <jats:italic>BAX</jats:italic>\n                    makes cells resistant to the apoptosis resulting from PUMA expression. These results suggest that the balance between PUMA and p21 is pivotal in determining the responses to p53 activation and provide a model for understanding the basis of p53 mutations in human cancer.\n                  </jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380013171044628866","@type":"Researcher","foaf:name":[{"@value":"Jian Yu"}],"jpcoar:affiliationName":[{"@value":"The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, The Howard Hughes Medical Institute, Baltimore, MD 21231; and University of Pittsburgh Cancer Institute, Hillman Cancer Center, Departments of Pathology and Pharmacology, University of Pittsburgh, Pittsburgh, PA 15213"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013171044628865","@type":"Researcher","foaf:name":[{"@value":"Zhenghe Wang"}],"jpcoar:affiliationName":[{"@value":"The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, The Howard Hughes Medical Institute, Baltimore, MD 21231; and University of Pittsburgh Cancer Institute, Hillman Cancer Center, Departments of Pathology and Pharmacology, University of Pittsburgh, Pittsburgh, PA 15213"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013171044628868","@type":"Researcher","foaf:name":[{"@value":"Kenneth W. Kinzler"}],"jpcoar:affiliationName":[{"@value":"The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, The Howard Hughes Medical Institute, Baltimore, MD 21231; and University of Pittsburgh Cancer Institute, Hillman Cancer Center, Departments of Pathology and Pharmacology, University of Pittsburgh, Pittsburgh, PA 15213"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013171044628864","@type":"Researcher","foaf:name":[{"@value":"Bert Vogelstein"}],"jpcoar:affiliationName":[{"@value":"The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, The Howard Hughes Medical Institute, Baltimore, MD 21231; and University of Pittsburgh Cancer Institute, Hillman Cancer Center, Departments of Pathology and Pharmacology, University of Pittsburgh, Pittsburgh, PA 15213"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013171044628867","@type":"Researcher","foaf:name":[{"@value":"Lin Zhang"}],"jpcoar:affiliationName":[{"@value":"The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, The Howard Hughes Medical Institute, Baltimore, MD 21231; and University of Pittsburgh Cancer Institute, Hillman Cancer Center, Departments of Pathology and Pharmacology, University of Pittsburgh, Pittsburgh, PA 15213"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00278424"},{"@type":"EISSN","@value":"10916490"}],"prism:publicationName":[{"@value":"Proceedings of the National Academy of Sciences"}],"dc:publisher":[{"@value":"Proceedings of the National Academy of Sciences"}],"prism:publicationDate":"2003-02-06","prism:volume":"100","prism:number":"4","prism:startingPage":"1931","prism:endingPage":"1936"},"reviewed":"false","url":[{"@id":"https://pnas.org/doi/pdf/10.1073/pnas.2627984100"}],"createdAt":"2003-02-18","modifiedAt":"2022-04-13","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050287685056633600","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"MCL1 inhibition is effective against a subset of small-cell lung cancer with high MCL1 and low BCL-XL expression"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285707490548992","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"The Trp53-Trp53inp1-Tnfrsf10b Pathway Regulates the Radiation Response of Mouse Spermatogonial Stem Cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360306905169756160","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"<i>BRAF</i>\n          V600E-induced distinct DNA damage response defines the therapeutic potential of p53 activation for <i>TP53</i> wild-type colorectal cancer"}]},{"@id":"https://cir.nii.ac.jp/crid/1390007525186050432","@type":"Article","relationType":["isReferencedBy","isCitedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Cell death in normal and abnormal development"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679879278976","@type":"Article","relationType":["isReferencedBy","isCitedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Mechanisms of neurotoxicity induced in the developing brain of mice and rats by DNA-damaging chemicals"}]},{"@id":"https://cir.nii.ac.jp/crid/1521980705173510016","@type":"Article","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@value":"How to cope with DNA damage induced by ionizing radiation and anti-cancer drugs?"},{"@language":"ja-Kana","@value":"How to cope with DNA damage induced by ionizing radiation and anti cancer drugs"},{"@language":"en","@value":"How to Cope with DNA Damage Induced by Ionizing Radiation and Anti-Cancer Drugs?(WHAT IS LIFE? THE NEXT 100 YEARS OF YUKAWA'S DREAM) :"}]},{"@id":"https://cir.nii.ac.jp/crid/1571417125150955648","@type":"Article","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Upregulation of BNIP3 by 5-aza-2'-deoxycytidine sensitizes pancreatic cancer cells to hypoxia-mediated cell death"}]},{"@id":"https://cir.nii.ac.jp/crid/1573950400153844224","@type":"Article","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Circadian gene mPer2 overexpression induces cancer cell apoptosis"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1073/pnas.2627984100"},{"@type":"CIA","@value":"80015837586"},{"@type":"CROSSREF","@value":"10.1016/j.stemcr.2014.08.006_references_DOI_RifMeey9yYXA2AaL8vf7jjWmdZF"},{"@type":"CROSSREF","@value":"10.1093/carcin/bgae040_references_DOI_RifMeey9yYXA2AaL8vf7jjWmdZF"},{"@type":"CROSSREF","@value":"10.1111/j.1741-4520.2007.00175.x_references_DOI_RifMeey9yYXA2AaL8vf7jjWmdZF"},{"@type":"CROSSREF","@value":"10.1038/s41419-020-2379-2_references_DOI_RifMeey9yYXA2AaL8vf7jjWmdZF"},{"@type":"CROSSREF","@value":"10.2131/jts.36.695_references_DOI_RifMeey9yYXA2AaL8vf7jjWmdZF"}]}