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.
2014-12-01
Source PublicationCANCER PREVENTION RESEARCH
ISSN1940-6207
Volume7Issue:12Pages:1270-1281
AbstractCheliensisin 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.
KeywordNaturally Occurring Substances Magnetic-resonance Spectroscopy Stem-bark Melodinus-henryi Conformational-analysis (+)-scholarisine Mechanism Leaves Seeds Camptothecin Indole Alkaloids Cytotoxicity Absolute Configuration Vinca Major
Subject AreaOncology
DOI10.1158/1940-6207.CAPR-14-0233
Indexed BySCI
Language英语
WOS IDWOS:000345742400011
Citation statistics
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/18488
Collection植物化学与西部植物资源持续利用国家重点实验室
Corresponding AuthorHuang,CS (reprint author),NYU,Sch Med,Nelson Inst Environm Med,57 Old Forge Rd,Tuxedo Pk,NY 10987 USA.
Affiliation1.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
Recommended Citation
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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