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

作者：Guo Changyue; Mi Jun; Brautigan David L; Larner James M^*

来源：Cellular Signalling, 2007, 19(3): 504-510.

DOI：10.1016/j.cellsig.2006.08.001

• ionizing radiation
• protein phosphatase-1
• HDAC1
• Rb

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 P-32 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 P-32 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.

• 出版日期2007-3