Abstract
G2/M checkpoint activation after DNA damage results in G2/M cell cycle arrest that allows time for DNA repair before the entry of cells into mitosis. Activation of G2/M checkpoint involves a series of signaling events, which include activation of ataxia telangiectecia-mutated and Rad3-related (ATR) and Chk1 kinases and inhibition of Cdc2/Cyclin B activity. Studies presented in this report show that serine (Ser)/threonine (Thr) protein phosphatase 2A (PP2A) has an important role in G2/M checkpoint activation in response to gamma-irradiation (IR) exposure. Using PP2A inhibitors, as well as siRNA targeting various forms of Ser/Thr protein phosphatases, results presented in this report show that specific PP2A inhibition abrogates IR-induced activation of ATR and Chk1 kinases, as well as phosphorylation of Cdc2-Tyr15, and attenuates IR-induced G2/M arrest. These results suggest an important regulation of PP2A on IR-induced G2/M checkpoint signaling response.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Ataxia Telangiectasia Mutated Proteins
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Breast Neoplasms / pathology
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Cell Cycle Proteins / metabolism
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Cell Cycle Proteins / physiology
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Cell Division / radiation effects*
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Cell Line, Tumor
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Checkpoint Kinase 1
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DNA-Binding Proteins / metabolism
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Enzyme Activation
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Female
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G2 Phase / radiation effects*
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Gamma Rays*
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Humans
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Protein Kinases / physiology
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Protein Phosphatase 2 / antagonists & inhibitors
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Protein Phosphatase 2 / physiology*
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Protein Serine-Threonine Kinases / metabolism
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Protein Serine-Threonine Kinases / physiology
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Receptors, Neuropeptide Y / antagonists & inhibitors
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Signal Transduction / physiology
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Tumor Suppressor Proteins / metabolism
Substances
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Cell Cycle Proteins
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DNA-Binding Proteins
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Receptors, Neuropeptide Y
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Tumor Suppressor Proteins
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neuropeptide Y4 receptor
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Protein Kinases
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ATM protein, human
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ATR protein, human
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Ataxia Telangiectasia Mutated Proteins
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CHEK1 protein, human
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Checkpoint Kinase 1
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Protein Serine-Threonine Kinases
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Protein Phosphatase 2