Dephosphorylation of DBC1 by Protein Phosphatase 4 Is Important for p53-Mediated Cellular Functions
| Autor: | Dong-Hyun Lee, Jarrod A. Marto, Jihye Lee, Guillaume Adelmant |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
DNA damage
Cell Survival Protein subunit Mutant Phosphatase Apoptosis Biology DNA damage response Article Dephosphorylation Cell Line Tumor Phosphoprotein Phosphatases Humans protein phosphatase 4 Phosphorylation Molecular Biology Adaptor Proteins Signal Transducing Kinase Cell Biology General Medicine Molecular biology dephosphorylation Tumor Suppressor Protein p53 deleted in breast cancer-1 |
| Zdroj: | Molecules and Cells |
| ISSN: | 0219-1032 |
| Popis: | Deleted in breast cancer-1 (DBC1) contributes to the regulation of cell survival and apoptosis. Recent studies demonstrated that DBC is phosphorylated at Thr454 by ATM/ATR kinases in response to DNA damage, which is a critical event for p53 activation and apoptosis. However, how DBC1 phosphorylation is regulated has not been studied. Here we show that protein phosphatase 4 (PP4) dephosphorylates DBC1, regulating its role in DNA damage response. PP4R2, a regulatory subunit of PP4, mediates the interaction between DBC1 and PP4C, a catalytic subunit. PP4C efficiently dephosphorylates pThr454 on DBC1 in vitro, and the depletion of PP4C/PP4R2 in cells alters the kinetics of DBC1 phosphorylation and p53 activation, and increases apoptosis in response to DNA damage, which are compatible with the expression of the phosphomimetic DBC-1 mutant (T454E). These suggest that the PP4-mediated dephosphorylation of DBC1 is necessary for efficient damage responses in cells. |
| Databáze: | OpenAIRE |
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