Protein phosphatase 2A has an essential role in the activation of γ-irradiation-induced G2 M checkpoint response

• Published in: Oncogene Vol. 29; no. 30; pp. 4317 - 4329
• Main Authors: Yan, Y, Cao, P T, Greer, P M, Nagengast, E S, Kolb, R H, Mumby, M C, Cowan, K H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.07.2010; Nature Publishing Group
• Subjects: 631/337/1427/2567; 631/80; 692/699/67/1347; Apoptosis; Ataxia; Ataxia telangiectasia; Ataxia Telangiectasia Mutated Proteins; Biological and medical sciences; Breast Neoplasms - pathology; Care and treatment; Cdc2 protein; Cell activation; Cell Biology; Cell cycle; Cell Cycle Proteins - metabolism; Cell Cycle Proteins - physiology; Cell cycle, cell proliferation; Cell Division - radiation effects; Cell Line, Tumor; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cellular signal transduction; Checkpoint Kinase 1; CHK1 protein; Cyclin B; Deoxyribonucleic acid; Diagnosis; DNA; DNA damage; DNA repair; DNA-Binding Proteins - metabolism; Enzyme Activation; Female; Fundamental and applied biological sciences. Psychology; G2 Phase - radiation effects; Gamma Rays; Genetic aspects; Health aspects; Human Genetics; Humans; I.R. radiation; Internal Medicine; Medicine; Medicine & Public Health; Methods; Mitosis; Molecular and cellular biology; Oncology; original-article; Phosphatase; Phosphatases; Phosphoprotein phosphatase; Phosphorylation; Properties; Protein Kinases - physiology; Protein phosphatase; Protein Phosphatase 2 - antagonists & inhibitors; Protein Phosphatase 2 - physiology; Protein-Serine-Threonine Kinases - metabolism; Protein-Serine-Threonine Kinases - physiology; Proteins; Radiotherapy; Receptors, Neuropeptide Y - antagonists & inhibitors; Signal Transduction - physiology; siRNA; Threonine; Tumor Suppressor Proteins - metabolism; γ Radiation; United States; Chk1/2; PP2A; ATM/ATR; irradiation and G2/M arrest; Enzyme; Phosphoprotein phosphatase; Phosphoric monoester hydrolases; Esterases; Activation; Carcinogenesis; Cell cycle; Irradiation; Hydrolases; Control point
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2010.187

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 γ-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.