Skip to main content

Protein phosphatase 5 is required for ATR-mediated checkpoint activation.

Publication ,  Journal Article
Zhang, J; Bao, S; Furumai, R; Kucera, KS; Ali, A; Dean, NM; Wang, X-F
Published in: Mol Cell Biol
November 2005

In response to DNA damage or replication stress, the protein kinase ATR is activated and subsequently transduces genotoxic signals to cell cycle control and DNA repair machinery through phosphorylation of a number of downstream substrates. Very little is known about the molecular mechanism by which ATR is activated in response to genotoxic insults. In this report, we demonstrate that protein phosphatase 5 (PP5) is required for the ATR-mediated checkpoint activation. PP5 forms a complex with ATR in a genotoxic stress-inducible manner. Interference with the expression or the activity of PP5 leads to impairment of the ATR-mediated phosphorylation of hRad17 and Chk1 after UV or hydroxyurea treatment. Similar results are obtained in ATM-deficient cells, suggesting that the observed defect in checkpoint signaling is the consequence of impaired functional interaction between ATR and PP5. In cells exposed to UV irradiation, PP5 is required to elicit an appropriate S-phase checkpoint response. In addition, loss of PP5 leads to premature mitosis after hydroxyurea treatment. Interestingly, reduced PP5 activity exerts differential effects on the formation of intranuclear foci by ATR and replication protein A, implicating a functional role for PP5 in a specific stage of the checkpoint signaling pathway. Taken together, our results suggest that PP5 plays a critical role in the ATR-mediated checkpoint activation.

Duke Scholars

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

November 2005

Volume

25

Issue

22

Start / End Page

9910 / 9919

Location

United States

Related Subject Headings

  • Ultraviolet Rays
  • Signal Transduction
  • S Phase
  • Replication Protein A
  • RNA, Small Interfering
  • Protein Serine-Threonine Kinases
  • Protein Kinases
  • Plasmids
  • Phosphorylation
  • Phosphoprotein Phosphatases
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhang, J., Bao, S., Furumai, R., Kucera, K. S., Ali, A., Dean, N. M., & Wang, X.-F. (2005). Protein phosphatase 5 is required for ATR-mediated checkpoint activation. Mol Cell Biol, 25(22), 9910–9919. https://doi.org/10.1128/MCB.25.22.9910-9919.2005
Zhang, Ji, Shideng Bao, Ryohei Furumai, Katerina S. Kucera, Ambereen Ali, Nicolas M. Dean, and Xiao-Fan Wang. “Protein phosphatase 5 is required for ATR-mediated checkpoint activation.Mol Cell Biol 25, no. 22 (November 2005): 9910–19. https://doi.org/10.1128/MCB.25.22.9910-9919.2005.
Zhang J, Bao S, Furumai R, Kucera KS, Ali A, Dean NM, et al. Protein phosphatase 5 is required for ATR-mediated checkpoint activation. Mol Cell Biol. 2005 Nov;25(22):9910–9.
Zhang, Ji, et al. “Protein phosphatase 5 is required for ATR-mediated checkpoint activation.Mol Cell Biol, vol. 25, no. 22, Nov. 2005, pp. 9910–19. Pubmed, doi:10.1128/MCB.25.22.9910-9919.2005.
Zhang J, Bao S, Furumai R, Kucera KS, Ali A, Dean NM, Wang X-F. Protein phosphatase 5 is required for ATR-mediated checkpoint activation. Mol Cell Biol. 2005 Nov;25(22):9910–9919.

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

November 2005

Volume

25

Issue

22

Start / End Page

9910 / 9919

Location

United States

Related Subject Headings

  • Ultraviolet Rays
  • Signal Transduction
  • S Phase
  • Replication Protein A
  • RNA, Small Interfering
  • Protein Serine-Threonine Kinases
  • Protein Kinases
  • Plasmids
  • Phosphorylation
  • Phosphoprotein Phosphatases