Protein phosphatase 2A has an essential role in the activation of gamma-irradiation-induced G2/M checkpoint response.
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.
Yan
Y
Y
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
Cao
P T
PT
Greer
P M
PM
Nagengast
E S
ES
Kolb
R H
RH
Mumby
M C
MC
Cowan
K H
KH
D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology; D002455:Cell Division / Q000528:radiation effects*; D045744:Cell Line, Tumor; D000071877:Checkpoint Kinase 1; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D016195:G2 Phase / Q000528:radiation effects*; D005720:Gamma Rays; D006801:Humans; D011494:Protein Kinases / Q000502:physiology; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D017476:Receptors, Neuropeptide Y; D025521:Tumor Suppressor Proteins; C109491:neuropeptide Y4 receptor; D011494:Protein Kinases; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases; D054648:Protein Phosphatase 2