| Crucial Role of c-Jun Phosphorylation at Ser63/73 Mediated by PHLPP Protein Degradation in the Cheliensisin A Inhibition of Cell Transformation | |
Zhu, Junlan1,2; Zhang, Jingjie1; Huang, Haishan1,2; Li, Jingxia1; Yu, Yonghui1; Jin, Honglei1,2; Li, Yang1,2; Deng, Xu3,4 ; Gao, Jimin2; Zhao, Qinshi3,4; Huang, Chuanshu1; Huang,CS (reprint author),NYU,Sch Med,Nelson Inst Environm Med,57 Old Forge Rd,Tuxedo Pk,NY 10987 USA.
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| 2014-12-01 | |
| 发表期刊 | CANCER PREVENTION RESEARCH
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| ISSN | 1940-6207 |
| 卷号 | 7期号:12页码:1270-1281 |
| 摘要 | Cheliensisin A (Chel A), as a novel styryl-lactone isolated from Goniothalamus cheliensis Hu, has been demonstrated to have an inhibition of EGF-induced Cl41 cell transformation via stabilizing p53 protein in a Chk1-dependent manner, suggesting its chemopreventive activity in our previous studies. However, its underlying molecular mechanisms have not been fully characterized yet. In the current study, we found that Chel A treatment could increase c-Jun protein phosphorylation and activation, whereas the inhibition of c-Jun phosphorylation, by ectopic expression of a dominant-negative mutant of c-Jun, TAM67, reversed the Chel A inhibition of EGF-induced cell transformation and impaired Chel A induction of p53 protein and apoptosis. Moreover, our results indicated that Chel A treatment led to a PHLPP downregulation by promoting PHLPP protein degradation. We also found that PHLPP could interact with and bind to c-Jun protein, whereas ectopic PHLPP expression blocked c-Jun activation, p53 protein and apoptotic induction by Chel A, and further reversed the Chel A inhibition of EGF-induced cell transformation. With the findings, we have demonstrated that Chel A treatment promotes a PHLPP protein degradation, which can bind to c-Jun and mediates c-Jun phosphorylation, and further leading to p53 protein induction, apoptotic responses, subsequently resulting in cell transformation inhibition and chemopreventive activity of Chel A. (C)2014 AACR. |
| 关键词 | Naturally Occurring Substances Magnetic-resonance Spectroscopy Stem-bark Melodinus-henryi Conformational-analysis (+)-scholarisine Mechanism Leaves Seeds Camptothecin Indole Alkaloids Cytotoxicity Absolute Configuration Vinca Major |
| 学科领域 | Oncology |
| DOI | 10.1158/1940-6207.CAPR-14-0233 |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000345742400011 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.kib.ac.cn/handle/151853/18488 |
| 专题 | 植物化学与西部植物资源持续利用国家重点实验室 |
| 通讯作者 | Huang,CS (reprint author),NYU,Sch Med,Nelson Inst Environm Med,57 Old Forge Rd,Tuxedo Pk,NY 10987 USA. |
| 作者单位 | 1.NYU, Sch Med, Nelson Inst Environm Med, Tuxedo Pk, NY 10987 USA 2.Wenzhou Med Univ, Sch Life Sci, Zhejiang Prov Key Lab Technol & Applicat Model Or, Wenzhou, Zhejiang, Peoples R China 3.Chinese Acad Sci, State Key Lab Phytochem & Plant Resources West Ch, Kunming, Peoples R China 4.Chinese Acad Sci, Kunming Inst Bot, Kunming, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhu, Junlan,Zhang, Jingjie,Huang, Haishan,et al. Crucial Role of c-Jun Phosphorylation at Ser63/73 Mediated by PHLPP Protein Degradation in the Cheliensisin A Inhibition of Cell Transformation[J]. CANCER PREVENTION RESEARCH,2014,7(12):1270-1281. |
| APA | Zhu, Junlan.,Zhang, Jingjie.,Huang, Haishan.,Li, Jingxia.,Yu, Yonghui.,...&Huang,CS .(2014).Crucial Role of c-Jun Phosphorylation at Ser63/73 Mediated by PHLPP Protein Degradation in the Cheliensisin A Inhibition of Cell Transformation.CANCER PREVENTION RESEARCH,7(12),1270-1281. |
| MLA | Zhu, Junlan,et al."Crucial Role of c-Jun Phosphorylation at Ser63/73 Mediated by PHLPP Protein Degradation in the Cheliensisin A Inhibition of Cell Transformation".CANCER PREVENTION RESEARCH 7.12(2014):1270-1281. |
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