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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Aaptamine, a spongean alkaloid, activates p21 promoter in a p53-independent manner
Shunji Aoki1, Dexin Kong, Hideaki Suna
1Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
Abstract:
Aaptamine, a benzonaphthyridine alkaloid was isolated from a marine sponge on the guidance of a bioassay using the transfected human osteosarcoma MG63 cells (MG63luc(+)). Aaptamine activated p21 promoter stably transfected in MG63 cells dose-dependently at the concentrations of 20-50microM. Expression of p21 and its mRNA in the wild-type MG63 cells also increased by aaptamine-treatment. Furthermore, the cell cycle of MG63 cells was arrested at the G2/M phase within 48h by the aaptamine-treatment. To analyze a responsive element of p21 promoter in the up-regulation of p21 by aaptamine, MG63 cells were transiently transfected with a series of the deleted or mutated promoter segments, and induction of luciferase with aaptamine treatment was examined by using these corresponding transfected cells. The activation of p21 promoter by aaptamine was led through acting Sp1 sites between -82 and -50bp in a p53-independent manner.
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