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Published on: June 6, 2017
Interference between p53 and cdc25C in cell cycle regulation
Sandra L Ruppenthal1, Andreas Noll, Claudia Götz
1Medical Biochemistry and Molecular Biology, University of the Saarland, D-66424 Homburg, Germany.
Abstract:
The eukaryotic cell cycle is regulated by a network of different protein kinases and phosphatases which are by various mechanisms linked to the growth suppressor p53. Cell cycle regulation is quite similar from yeast to man. Although there is no endogenous p53 in yeast expression of human p53 led to growth arrest of yeast cells which can be suppressed by simultaneous overexpression of cdc25C, a phosphatase regulating entry into mitosis. Herein, we show that overexpression of cdc25C in mammalian cells is insufficient in suppressing a p53 induced growth arrest. We further show that p53 is co-immunoprecipitated with cdc25C and p53 inhibits the cdc25C phosphatase activity in a dose-dependent manner. Thus, our data show that p53 like other binding partners of cdc25C, regulates entry into mitosis by binding to cdc25C.
Insights
The tumor suppressor p53 inhibits the phosphatase cdc25C, regulating entry into mitosis. This binding interaction is crucial for cell cycle control in mammalian cells, unlike in yeast.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- The eukaryotic cell cycle is tightly regulated by protein kinases and phosphatases.
- The tumor suppressor p53 is linked to cell cycle regulation through various mechanisms.
- cdc25C is a key phosphatase controlling entry into mitosis.
Purpose of the Study:
- To investigate the interaction between p53 and cdc25C in mammalian cells.
- To determine if cdc25C overexpression can suppress p53-induced growth arrest in mammals.
- To elucidate the role of p53 in regulating cdc25C phosphatase activity.
Main Methods:
- Co-immunoprecipitation assays to detect p53-cdc25C interaction.
- Overexpression studies of cdc25C in mammalian cells.
- Enzyme activity assays to measure cdc25C phosphatase activity in the presence of p53.
Main Results:
- Overexpression of cdc25C did not suppress p53-induced growth arrest in mammalian cells.
- p53 was found to co-immunoprecipitate with cdc25C.
- p53 inhibited cdc25C phosphatase activity in a dose-dependent manner.
Conclusions:
- p53 directly interacts with cdc25C.
- p53 regulates entry into mitosis by inhibiting cdc25C phosphatase activity.
- This mechanism highlights a conserved role for p53 in cell cycle control.
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