Structural convergence of unstructured p53 family transactivation domains in mdm2 recognition

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dc.contributor.authorJae-Sun Shin-
dc.contributor.authorJi Hyang Ha-
dc.contributor.authorDong Hwa Lee-
dc.contributor.authorK S Ryu-
dc.contributor.authorKwang-Hee Bae-
dc.contributor.authorByoung Chul Park-
dc.contributor.authorSung Goo Park-
dc.contributor.authorG S Yi-
dc.contributor.authorSeung-Wook Chi-
dc.date.accessioned2017-04-19T10:02:13Z-
dc.date.available2017-04-19T10:02:13Z-
dc.date.issued2015-
dc.identifier.issn15384101-
dc.identifier.uri10.1080/15384101.2014.998056ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/12485-
dc.description.abstractThe p53, p63, and p73 proteins belong to the p53 family of transcription factors, which play key roles in tumor suppression. Although the transactivation domains (TADs) of the p53 family are intrinsically disordered, these domains are commonly involved in the regulatory interactions with mouse double minute 2 (MDM2). In this study, we determined the solution structure of the p73TAD peptide in complex with MDM2 using NMR spectroscopy and biophysically characterized the interactions between the p53 family TAD peptides and MDM2. In combination with mutagenesis data, the complex structures revealed remarkably close mimicry of the MDM2 recognition mechanism among the p53 family TADs. Upon binding with MDM2, the intrinsically disordered p73TAD and p63TAD peptides adopt an amphipathic a-helical conformation, which is similar to the conformation of p53TAD, although the a-helical content induced by MDM2 binding varies. With isothermal titration calorimetry (ITC) and circular dichroism (CD) data, our biophysical characterization showed that p73TAD resembles p53TAD more closely than p63TAD in terms of helical stability, MDM2 binding affinity, and phosphorylation effects on MDM2 binding. Therefore, our structural information may be useful in establishing alternative anticancer strategies that exploit the activation of the p73 pathway against human tumors bearing p53 mutations.-
dc.publisherT&F (Taylor & Francis)-
dc.titleStructural convergence of unstructured p53 family transactivation domains in mdm2 recognition-
dc.title.alternativeStructural convergence of unstructured p53 family transactivation domains in mdm2 recognition-
dc.typeArticle-
dc.citation.titleCell Cycle-
dc.citation.number4-
dc.citation.endPage543-
dc.citation.startPage533-
dc.citation.volume14-
dc.contributor.affiliatedAuthorKwang-Hee Bae-
dc.contributor.affiliatedAuthorByoung Chul Park-
dc.contributor.affiliatedAuthorSung Goo Park-
dc.contributor.affiliatedAuthorSeung-Wook Chi-
dc.contributor.alternativeName신재선-
dc.contributor.alternativeName하지향-
dc.contributor.alternativeName이동화-
dc.contributor.alternativeName유경석-
dc.contributor.alternativeName배광희-
dc.contributor.alternativeName박병철-
dc.contributor.alternativeName박성구-
dc.contributor.alternativeName이관수-
dc.contributor.alternativeName지승욱-
dc.identifier.bibliographicCitationCell Cycle, vol. 14, no. 4, pp. 533-543-
dc.identifier.doi10.1080/15384101.2014.998056-
dc.subject.keywordComplex structure-
dc.subject.keywordMDM2-
dc.subject.keywordNMR-
dc.subject.keywordP53 family-
dc.subject.keywordP73-
dc.subject.keywordTransactivation domain-
dc.subject.localComplex structure-
dc.subject.localMDM2-
dc.subject.localNMR-
dc.subject.localP53 family-
dc.subject.localP73-
dc.subject.localp73-
dc.subject.localTransactivation domain-
dc.description.journalClassY-
Appears in Collections:
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
Division of Biomedical Research > 1. Journal Articles
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