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题名: Identification and validation of p50 as the cellular target of eriocalyxin B
作者: Kong, Ling-Mei1, 2; Deng, Xu1; Zuo, Zhi-Li1; null(孙汉董)1; null(赵勤实)1; null(李艳)1
刊名: ONCOTARGET
出版日期: 2014-11-30
卷号: 5, 期号:22, 页码:11354-11364
关键词: EriB ; activity-based probes ; p50 ; NF-kappa B signaling ; apoptosis
文章类型: Article
英文摘要: As an ent-kaurene diterpenoid isolated from Isodon eriocalyx var. Laxiflora, Eriocalyxin B (EriB) possesses potent bioactivity of antitumor and anti-autoimmune inflammation, which has been suggested to work through inhibition of NF-kappaB (NF-kappa B) signaling. However, the direct target of EriB remains elusive. In this study, we showed that EriB induced apoptosis is associated with the inhibition of NF-kappa B signaling in SMMC-7721 hepatocellular carcinoma cells. With activity-based probe profiling, we identified p50 protein as the direct target of EriB. We showed that cysteine 62 is the critical residue of p50 for EriB binding through the alpha, beta-unsaturated ketones. As the result, EriB selectively blocks the binding between p50 and the response elements, whereas having no effect on the dimerization or the nuclear translocation of p50 and p65. SiRNA mediated knockdown of p50 attenuated the apoptosis induced by EriB in SMMC-7721 cells. Taken together, our studies illustrated that EriB induces cancer cell apoptosis through interfering with the binding between NF-kappa B and the response elements by targeting the cysteine 62 of p50, which highlights its potential for the development of p50 targeted cancer therapeutic agents.
类目[WOS]: Oncology ; Cell Biology
研究领域[WOS]: Oncology ; Cell Biology
关键词[WOS]: NF-KAPPA-B ; CRYSTAL-STRUCTURE ; APOPTOSIS ; CELLS ; DNA ; ACTIVATION ; INFLAMMATION ; HETERODIMER ; DEGRADATION ; HOMODIMER
收录类别: SCI
语种: 英语
WOS记录号: WOS:000348037400038
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.kib.ac.cn/handle/151853/20409
Appears in Collections:植物化学与西部植物资源持续利用国家重点实验室_期刊论文

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作者单位: 1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Peoples R China
2.Chinese Acad Sci, Grad Univ, Beijing 100039, Peoples R China
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