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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Tang, X; Hui, Z-G; Cui, X-L; Garg, R; Kastan, MB; Xu, B

Published Date

  • April 2008

Published In

Volume / Issue

  • 28 / 8

Start / End Page

  • 2559 - 2566

PubMed ID

  • 18250156

Pubmed Central ID

  • 18250156

Electronic International Standard Serial Number (EISSN)

  • 1098-5549

Digital Object Identifier (DOI)

  • 10.1128/MCB.01711-07

Language

  • eng

Conference Location

  • United States