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

Ying Yan, P. T. Cao, P. M. Greer, E. S. Nagengast, R. H. Kolb, M. C. Mumby, Kenneth H Cowan

Research output: Contribution to journalArticle

40 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)4317-4329
Number of pages13
JournalOncogene
Volume29
Issue number30
DOIs
StatePublished - Jul 29 2010

Fingerprint

Protein Phosphatase 2
Ataxia
G2 Phase Cell Cycle Checkpoints
Cyclin B
Phosphoprotein Phosphatases
Threonine
Mitosis
DNA Repair
Serine
Small Interfering RNA
DNA Damage
Phosphorylation
Checkpoint Kinase 1

Keywords

  • ATM/ATR
  • Chk1/2
  • PP2A
  • irradiation and G2/M arrest

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Protein phosphatase 2A has an essential role in the activation of γ-irradiation-induced G2/M checkpoint response. / Yan, Ying; Cao, P. T.; Greer, P. M.; Nagengast, E. S.; Kolb, R. H.; Mumby, M. C.; Cowan, Kenneth H.

In: Oncogene, Vol. 29, No. 30, 29.07.2010, p. 4317-4329.

Research output: Contribution to journalArticle

Yan, Ying ; Cao, P. T. ; Greer, P. M. ; Nagengast, E. S. ; Kolb, R. H. ; Mumby, M. C. ; Cowan, Kenneth H. / Protein phosphatase 2A has an essential role in the activation of γ-irradiation-induced G2/M checkpoint response. In: Oncogene. 2010 ; Vol. 29, No. 30. pp. 4317-4329.
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