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dc.contributor.authorZhao, Bi-xing
dc.contributor.authorChen, Hang-zi
dc.contributor.authorLei, Na-zi
dc.contributor.authorLi, Gui-deng
dc.contributor.authorZhao, Wen-xiu
dc.contributor.authorZhan, Yan-yan
dc.contributor.authorLiu, Bo
dc.contributor.authorLin, Sheng-cai
dc.contributor.author林圣彩
dc.contributor.authorWu, Qiao
dc.contributor.author吴乔
dc.date.accessioned2011-08-27T08:02:17Z
dc.date.available2011-08-27T08:02:17Z
dc.date.issued2006
dc.identifier.citationThe EMBO Journal (2006) 25, 5703 - 5715zh_CN
dc.identifier.issn0261-4189
dc.identifier.urihttp://dx.doi.org/doi:10.1038/sj.emboj.7601435
dc.identifier.urihttps://dspace.xmu.edu.cn/handle/2288/10694
dc.description.abstractMDM2 is an oncoprotein whose transforming potential is activated by overexpression. The expression level of MDM2 is negatively regulated by orphan receptor TR3 that mainly acts as a transcriptional factor to regulate gene expression. However, the underlying mechanism is largely unclear. Here, we present the first evidence that inhibition of TR3 on MDM2 is mediated by p53. We found that TR3 directly interacts with p53 but not MDM2, and such interaction is critical for TR3 to inhibit MDM2 expression. TR3 downregulates p53 transcriptional activity by blocking its acetylation, leading to a decrease on the transcription level of MDM2. Furthermore, TR3 binding to p53 obstructs its ubiquitination and degradation induced by MDM2, resulting in the MDM2 ubiquitination and degradation. In addition, TR3 could enhance p53-mediated apoptosis induced by UV irradiation. Taken together, our findings demonstrate that p53 mediates the suppression of TR3 on MDM2 at both transcriptional and post-transcriptional level and suggest TR3 as a potential target to develop new anticancer agents that restrict MDM2-induced tumor progression.zh_CN
dc.language.isoenzh_CN
dc.publisherNATURE PUBLISHING GROUPzh_CN
dc.subjectacetylationzh_CN
dc.subjectMDM2 (mouse double minute) proteinzh_CN
dc.subjectorphan receptor TR3zh_CN
dc.subjecttumor suppressor p53zh_CN
dc.subjectubiquitinationzh_CN
dc.titlep53 mediates the negative regulation of MDM2 by orphan receptor TR3zh_CN
dc.typeArticlezh_CN


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