title: Dephosphorylation of DBC1 by Protein Phosphatase 4 Is Important for p53-Mediated Cellular Functions.
abstract: 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.
authors.affiliation: Department of Biological Sciences, College of Science, Chonnam National University, Gwangju 500-757, Korea.
authors.forename: Jihye
authors.initials: J
authors.lastname: Lee
authors.forename: Guillaume
authors.initials: G
authors.lastname: Adelmant
authors.forename: Jarrod A
authors.initials: JA
authors.lastname: Marto
authors.affiliation: Department of Biological Sciences, College of Science, Chonnam National University, Gwangju 500-757, Korea.
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D006801:Humans; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C527450:CCAR2 protein, human; D016159:Tumor Suppressor Protein p53; D010749:Phosphoprotein Phosphatases; C080406:protein phosphatase 4
keywords: DNA damage response; deleted in breast cancer-1; dephosphorylation; protein phosphatase 4