Targeting of p53 peptide analogues to anti-apoptotic Bcl-2 family proteins as revealed by NMR spectroscopy

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dc.contributor.authorJ S Shin-
dc.contributor.authorJi-Hyang Ha-
dc.contributor.authorSeung-Wook Chi-
dc.date.accessioned2017-04-19T09:51:14Z-
dc.date.available2017-04-19T09:51:14Z-
dc.date.issued2014-
dc.identifier.issn0006291X-
dc.identifier.uri10.1016/j.bbrc.2013.12.054ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/11853-
dc.description.abstractInhibition of the interaction between the p53 tumor suppressor and its negative regulator MDM2 is of great importance to cancer therapy. The anti-apoptotic Bcl-2 family proteins are also attractive anti-cancer molecular targets, as they are key regulators of apoptotic cell death. Previously, we reported the interactions between the p53 transactivation domain (p53TAD) and diverse members of the anti-apoptotic Bcl-2 family proteins. In this study, we investigated the binding of MDM2-inhibiting p53TAD peptide analogues, p53-MDM2/MDMX inhibitor (PMI) and pDI, with anti-apoptotic Bcl-2 family proteins, Bcl-XL and Bcl-2, by using NMR spectroscopy. The NMR chemical shift perturbation data demonstrated the direct binding of the p53 peptide analogues to Bcl-XL and Bcl-2 and showed that the PMI and pDI peptides bind to a conserved hydrophobic groove of the anti-apoptotic Bcl-2 family proteins. Furthermore, the structural model of the Bcl-XL/PMI peptide complex showed that the binding mode of the PMI peptide is highly similar to that of pro-apoptotic Bcl-2 homology 3 (BH3) peptides. Finally, our structural comparison provided a molecular basis for how the same PMI peptide can bind to two distinct anti-cancer target proteins Bcl-XL and MDM2, which may have potential applications for multi-targeting cancer therapy.-
dc.publisherElsevier-
dc.titleTargeting of p53 peptide analogues to anti-apoptotic Bcl-2 family proteins as revealed by NMR spectroscopy-
dc.title.alternativeTargeting of p53 peptide analogues to anti-apoptotic Bcl-2 family proteins as revealed by NMR spectroscopy-
dc.typeArticle-
dc.citation.titleBiochemical and Biophysical Research Communications-
dc.citation.number3-
dc.citation.endPage887-
dc.citation.startPage882-
dc.citation.volume443-
dc.contributor.affiliatedAuthorSeung-Wook Chi-
dc.contributor.alternativeName신재선-
dc.contributor.alternativeName하지향-
dc.contributor.alternativeName지승욱-
dc.identifier.bibliographicCitationBiochemical and Biophysical Research Communications, vol. 443, no. 3, pp. 882-887-
dc.identifier.doi10.1016/j.bbrc.2013.12.054-
dc.subject.keywordBcl-2 family proteins-
dc.subject.keywordCancer therapy-
dc.subject.keywordMDM2-
dc.subject.keywordMulti-targeting-
dc.subject.keywordNMR spectroscopy-
dc.subject.keywordp53 Peptide analogue-
dc.subject.keywordpDI-
dc.subject.keywordPMI-
dc.subject.localBcl-2 family proteins-
dc.subject.localBcl-2 family protein-
dc.subject.localCancer therapy-
dc.subject.localMDM2-
dc.subject.localMulti-targeting-
dc.subject.localNMR spectroscopy-
dc.subject.localp53 Peptide analogue-
dc.subject.localpDI-
dc.subject.localPMI-
dc.description.journalClassY-
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Division of Biomedical Research > 1. Journal Articles
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