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A novel ATM-dependent pathway regulates protein phosphatase 1 in response to DNA damage.

Publication ,  Journal Article
Tang, X; Hui, Z-G; Cui, X-L; Garg, R; Kastan, MB; Xu, B
Published in: Mol Cell Biol
April 2008

Protein phosphatase 1 (PP1), a major protein phosphatase important for a variety of cellular responses, is activated in response to ionizing irradiation (IR)-induced DNA damage. Here, we report that IR induces the rapid dissociation of PP1 from its regulatory subunit inhibitor-2 (I-2) and that the process requires ataxia-telangiectasia mutated (ATM), a protein kinase central to DNA damage responses. In response to IR, ATM phosphorylates I-2 on serine 43, leading to the dissociation of the PP1-I-2 complex and the activation of PP1. Furthermore, ATM-mediated I-2 phosphorylation results in the inhibition of the Aurora-B kinase, the down-regulation of histone H3 serine 10 phosphorylation, and the activation of the G(2)/M checkpoint. Collectively, the results of these studies demonstrate a novel pathway that links ATM, PP1, and I-2 in the cellular response to DNA damage.

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Published In

Mol Cell Biol

DOI

EISSN

1098-5549

Publication Date

April 2008

Volume

28

Issue

8

Start / End Page

2559 / 2566

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Signal Transduction
  • Sequence Homology, Amino Acid
  • Sequence Alignment
  • Protein Serine-Threonine Kinases
  • Protein Phosphatase 1
  • Protein Binding
  • Phosphorylation
  • Molecular Sequence Data
  • Humans
 

Citation

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Tang, X., Hui, Z.-G., Cui, X.-L., Garg, R., Kastan, M. B., & Xu, B. (2008). A novel ATM-dependent pathway regulates protein phosphatase 1 in response to DNA damage. Mol Cell Biol, 28(8), 2559–2566. https://doi.org/10.1128/MCB.01711-07
Tang, Xi, Zhou-Guang Hui, Xiao-Li Cui, Renu Garg, Michael B. Kastan, and Bo Xu. “A novel ATM-dependent pathway regulates protein phosphatase 1 in response to DNA damage.Mol Cell Biol 28, no. 8 (April 2008): 2559–66. https://doi.org/10.1128/MCB.01711-07.
Tang X, Hui Z-G, Cui X-L, Garg R, Kastan MB, Xu B. A novel ATM-dependent pathway regulates protein phosphatase 1 in response to DNA damage. Mol Cell Biol. 2008 Apr;28(8):2559–66.
Tang, Xi, et al. “A novel ATM-dependent pathway regulates protein phosphatase 1 in response to DNA damage.Mol Cell Biol, vol. 28, no. 8, Apr. 2008, pp. 2559–66. Pubmed, doi:10.1128/MCB.01711-07.
Tang X, Hui Z-G, Cui X-L, Garg R, Kastan MB, Xu B. A novel ATM-dependent pathway regulates protein phosphatase 1 in response to DNA damage. Mol Cell Biol. 2008 Apr;28(8):2559–2566.

Published In

Mol Cell Biol

DOI

EISSN

1098-5549

Publication Date

April 2008

Volume

28

Issue

8

Start / End Page

2559 / 2566

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Signal Transduction
  • Sequence Homology, Amino Acid
  • Sequence Alignment
  • Protein Serine-Threonine Kinases
  • Protein Phosphatase 1
  • Protein Binding
  • Phosphorylation
  • Molecular Sequence Data
  • Humans