{"@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/1361981470170170880.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1101/gad.304071.117"}},{"identifier":{"@type":"URI","@value":"https://syndication.highwire.org/content/doi/10.1101/gad.304071.117"}}],"dc:title":[{"@value":"Wild-type and cancer-related p53 proteins are preferentially degraded by MDM2 as dimers rather than tetramers"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>The p53 tumor suppressor protein is the most well studied as a regulator of transcription in the nucleus, where it exists primarily as a tetramer. However, there are other oligomeric states of p53 that are relevant to its regulation and activities. In unstressed cells, p53 is normally held in check by MDM2 that targets p53 for transcriptional repression, proteasomal degradation, and cytoplasmic localization. Here we discovered a hydrophobic region within the MDM2 N-terminal domain that binds exclusively to the dimeric form of the p53 C-terminal domain in vitro. In cell-based assays, MDM2 exhibits superior binding to, hyperdegradation of, and increased nuclear exclusion of dimeric p53 when compared with tetrameric wild-type p53. Correspondingly, impairing the hydrophobicity of the newly identified N-terminal MDM2 region leads to p53 stabilization. Interestingly, we found that dimeric mutant p53 is partially unfolded and is a target for ubiquitin-independent degradation by the 20S proteasome. Finally, forcing certain tumor-derived mutant forms of p53 into dimer configuration results in hyperdegradation of mutant p53 and inhibition of p53-mediated cancer cell migration. Gaining insight into different oligomeric forms of p53 may provide novel approaches to cancer therapy.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1381981470170171009","@type":"Researcher","foaf:name":[{"@value":"Chen Katz"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981470170170880","@type":"Researcher","foaf:name":[{"@value":"Ana Maria Low-Calle"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981470170170882","@type":"Researcher","foaf:name":[{"@value":"Joshua H. Choe"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981470170171011","@type":"Researcher","foaf:name":[{"@value":"Oleg Laptenko"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981470170170883","@type":"Researcher","foaf:name":[{"@value":"David Tong"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981470170170884","@type":"Researcher","foaf:name":[{"@value":"Jazmine-Saskya N. Joseph-Chowdhury"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981470170171008","@type":"Researcher","foaf:name":[{"@value":"Francesca Garofalo"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981470170171012","@type":"Researcher","foaf:name":[{"@value":"Yan Zhu"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981470170170881","@type":"Researcher","foaf:name":[{"@value":"Assaf Friedler"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981470170171010","@type":"Researcher","foaf:name":[{"@value":"Carol Prives"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"08909369"},{"@type":"EISSN","@value":"15495477"}],"prism:publicationName":[{"@value":"Genes & Development"}],"dc:publisher":[{"@value":"Cold Spring Harbor Laboratory"}],"prism:publicationDate":"2018-03-01","prism:volume":"32","prism:number":"5-6","prism:startingPage":"430","prism:endingPage":"447"},"reviewed":"false","url":[{"@id":"https://syndication.highwire.org/content/doi/10.1101/gad.304071.117"}],"createdAt":"2018-03-16","modifiedAt":"2021-11-17","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1361975841501699072","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"A muscle-specific calpain, CAPN3, forms a homotrimer"}]},{"@id":"https://cir.nii.ac.jp/crid/1361975843725098112","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Stepwise multipolyubiquitination of p53 by the E6AP-E6 ubiquitin ligase complex"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1101/gad.304071.117"},{"@type":"CROSSREF","@value":"10.1016/j.bbapap.2020.140411_references_DOI_Kl6Fg50aKt1ns9jdCHdMv1c81G9"},{"@type":"CROSSREF","@value":"10.1074/jbc.ra119.008374_references_DOI_Kl6Fg50aKt1ns9jdCHdMv1c81G9"}]}