ATM regulates ionizing radiation-induced disruption of HDAC1:PP1:Rb complexes.

Ionizing radiation elicits signaling events that coordinate DNA repair and interruption of cell cycle progression. We previously demonstrated that ionizing radiation (IR) of cells activates nuclear protein phosphatase-1 (PP1) by promoting dephosphorylation of Thr320, an inhibitory site in the enzyme and that the ATM kinase is required for this response. ...
We sought to identify potential targets of IR-activated PP1. Untreated and IR-treated Jurkat cells were labeled with (32)P orthophosphate, and nuclear extracts were subjected to microcystin affinity chromatography to recover phosphatase complexes that were analyzed by 2D-PAGE and mass spectrometry. Several proteins associated with protein phosphatases demonstrated a significant decrease in (32)P intensity following IR, and one of these was identified as HDAC1. Co-immunoprecipitation revealed complexes containing PP1 with HDAC1 and Rb in cell extracts. In response to IR, there was an ATM-dependent activation of PP1, dephosphorylation of HDAC1, dissociation of HDAC1-PP1-Rb complexes and increased HDAC1 activity. These results suggest that IR regulates HDAC1 phosphorylation and activity through ATM-dependent activation of PP1.
Mesh Terms:
Cell Cycle Proteins, Cell Line, Transformed, DNA-Binding Proteins, Enzyme Activation, Histone Deacetylase 1, Histone Deacetylases, Humans, Immunoprecipitation, Jurkat Cells, Microcystins, Models, Biological, Phosphoprotein Phosphatases, Protein Phosphatase 1, Protein-Serine-Threonine Kinases, Radiation, Ionizing, Retinoblastoma Protein, Tumor Suppressor Proteins
Cell. Signal.
Date: Mar. 01, 2007
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