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- Title
Identification of a small molecule 1,4-bis-[4-(3-phenoxy-propoxy)-but-2-ynyl]-piperazine as a novel inhibitor of the transcription factor p53.
- Authors
Liu, Xin; Zhang, Ying; Tong, Man; Liu, Xiu-ying; Luo, Guan-zheng; Xie, Dong-fang; Ren, Shao-fang; Bai, Dong-hui; Wang, Liu; Zhou, Qi; Wang, Xiu-jie
- Abstract
Aim:To identify novel small compound inhibitor of p53 protein.Methods:Mouse embryonic fibroblasts (MEF) and mouse embryonic stem (ES) cells were tested. Cell proliferation rate was determined using a Cell Proliferation Kit. The mRNA and protein levels of p53-related genes were measured using real-time PCR and Western blotting, respectively. Global response in the p53 signaling network was analyzed using Illumina whole-genome expression BeadChips.Results:Treatment of MEF cells with a small molecule 1,4-bis-[4-(3-phenoxy-propoxy)-but-2-ynyl]-piperazine (G5) at 10 μmol/L for 24 h markedly reduced the mRNA and protein levels of the p53 downstream genes MDM2 and p21. In G5-treated ES cells, a total of 372 differentially expressed genes were identified, and 18 among them were direct downstream genes of p53; 6 out of 9 p53-repressed genes were upregulated, and 5 out of 9 p53-activated genes were downregulated. In both MEF cells and ES cells, treatment of with G5 (10 μmol/L) up to 48 h neither affected the proliferation rate nor caused morphological alterations.Conclusion:G5 inhibits p53 activity and simultaneously preserves the normal growth and proliferation of cells, therefore is a new compound for studies of p53-mediated cell manipulation.
- Subjects
TRANSCRIPTION factors; PIPERAZINE; FIBROBLASTS; P53 antioncogene; CELL proliferation; MESSENGER RNA; EMBRYONIC stem cell research
- Publication
Acta Pharmacologica Sinica, 2013, Vol 34, Issue 6, p805
- ISSN
1671-4083
- Publication type
Article
- DOI
10.1038/aps.2013.61