Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.


The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: Crucial role of c-Jun phosphorylation at Ser63/73 mediated by PHLPP protein degradation in the cheliensisin a inhibition of cell transformation.

Authors: Zhu, Junlan; Zhang, Jingjie; Huang, Haishan; Li, Jingxia; Yu, Yonghui; Jin, Honglei; Li, Yang; Deng, Xu; Gao, Jimin; Zhao, Qinshi; Huang, Chuanshu

Published In Cancer Prev Res (Phila), (2014 Dec)

Abstract: 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.

PubMed ID: 25281487 Exiting the NIEHS site

MeSH Terms: Animals; Blotting, Western; Cell Proliferation; Cell Transformation, Neoplastic/drug effects*; Cell Transformation, Neoplastic/pathology; Cells, Cultured; Epidermal Growth Factor/pharmacology; Epidermis/cytology; Epidermis/drug effects*; Epidermis/metabolism; Epoxy Compounds/pharmacology*; Flow Cytometry; Immunoprecipitation; Mice; Nuclear Proteins/metabolism*; Phosphoprotein Phosphatases/metabolism*; Phosphorylation/drug effects; Proteolysis/drug effects*; Proto-Oncogene Proteins c-jun/metabolism*; Pyrones/pharmacology*; RNA, Messenger/genetics; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Serine/metabolism; Signal Transduction/drug effects*; Tumor Suppressor Protein p53/metabolism

to Top