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

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

Research output: Contribution to journalArticle

42 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'Protein phosphatase 2A has an essential role in the activation of γ-irradiation-induced G2/M checkpoint response'. Together they form a unique fingerprint.

  • Cite this