Identification and validation of p50 as the cellular target of eriocalyxin B
Kong, Ling-Mei1,2; Deng, Xu1; Zuo, Zhi-Li1; Sun, Han-Dong1; Zhao, Qin-Shi1; Li, Yan1
2014-11-30
发表期刊ONCOTARGET
卷号5期号:22页码:11354-11364
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.
关键词Erib Activity-based Probes P50 Nf-kappa b Signaling Apoptosis
收录类别SCI
语种英语
WOS研究方向Oncology ; Cell Biology
WOS类目Oncology ; Cell Biology
WOS记录号WOS:000348037400038
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文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/20409
专题植物化学与西部植物资源持续利用国家重点实验室
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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Kong, Ling-Mei,Deng, Xu,Zuo, Zhi-Li,et al. Identification and validation of p50 as the cellular target of eriocalyxin B[J]. ONCOTARGET,2014,5(22):11354-11364.
APA Kong, Ling-Mei,Deng, Xu,Zuo, Zhi-Li,Sun, Han-Dong,Zhao, Qin-Shi,&Li, Yan.(2014).Identification and validation of p50 as the cellular target of eriocalyxin B.ONCOTARGET,5(22),11354-11364.
MLA Kong, Ling-Mei,et al."Identification and validation of p50 as the cellular target of eriocalyxin B".ONCOTARGET 5.22(2014):11354-11364.
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