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15-Deoxy-Δ12,14-prostaglandin J2 stabilizes, but functionally inactivates p53 by binding to the cysteine 277 residue

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dc.contributor.authorKim, Dohyun-
dc.contributor.authorKim, Eun-hee-
dc.contributor.authorNa, Hye-kyung-
dc.contributor.authorSun, Yi-
dc.contributor.authorSurh, Young-Joon-
dc.date.accessioned2021-01-31T09:24:23Z-
dc.date.available2021-01-31T09:24:23Z-
dc.date.issued2010-04-
dc.identifier.citationOncogene, Vol.29 No.17, pp.2560-2576-
dc.identifier.issn0950-9232-
dc.identifier.other2632-
dc.identifier.urihttps://hdl.handle.net/10371/172646-
dc.description.abstract15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), a representative cyclopentenone prostaglandin, has many interesting biological effects. In this study, treatment of human breast cancer cells (MCF-7) with 15d-PGJ(2) led to accumulation of p53 protein. However, the p53 DNA binding and its transcriptional activity were significantly reduced. 15d-PGJ(2) directly modified p53 as verified by reacting recombinant p53 with biotinylated 15d-PGJ(2). 9,10-Dihydro-15-deoxy-Delta(12,14)-prostaglandin J(2) lacking the electrophilic alpha,beta-unsaturated functionality failed to inhibit p53 DNA binding as well as to modify p53. Moreover, by conducting an in vitro [S-35]-labeled p53 translation assay, we identified cysteine 277 as a putative site of p53 modification by 15d-PGJ(2). The DNA-binding ability of a mutant p53 in which cysteine 277 was substituted by alanine was virtually unaffected by 15d-PGJ(2). Likewise, p53 binding activity of biotinylated 15d-PGJ(2) was abolished in mutant cells. In addition, cells expressing wild-type p53 exhibited p53 protein stability to a greater extent than mutant C277A cells. In conclusion, 15d-PGJ(2) can undergo nucleophilic addition to p53, presumably at the cysteine 277 residue, rendering this tumor suppressor less susceptible to proteasomal degradation. Oncogene (2010) 29, 2560-2576; doi:10.1038/onc.2010.8; published online 8 March 2010-
dc.subjectcyclopentenone prostaglandin-
dc.subject15-deoxy-Delta(12,14)-prostaglandin J(2)-
dc.subjectp53-
dc.subjectthiol modification-
dc.title15-Deoxy-Δ12,14-prostaglandin J2 stabilizes, but functionally inactivates p53 by binding to the cysteine 277 residue-
dc.typeArticle-
dc.contributor.AlternativeAuthor서영준-
dc.identifier.doi10.1038/onc.2010.8-
dc.citation.journaltitleOncogene-
dc.identifier.scopusid2-s2.0-77951880356-
dc.citation.endpage2576-
dc.citation.number17-
dc.citation.startpage2560-
dc.citation.volume29-
dc.identifier.urlhttps://www.nature.com/articles/onc20108-
dc.identifier.rimsid2632-
dc.identifier.sci000277169400011-
dc.contributor.affiliatedAuthorSurh, Young-Joon-
Appears in Collections:
Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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