Interaction between ATM protein and c-Abl in response to DNA damage (original) (raw)

Nature volume 387, pages 520–523 (1997)Cite this article

Abstract

The gene mutated in the autosomal recessive disorder ataxia telangiectasia (AT), designated ATM (for 'AT mutated'), is a member of a family of phosphatidylinositol-3-kinase-like enzymes that are involved in cell-cycle control, meiotic recombination, telomere length monitoring and DNA-damage response1–4. Previous results have demonstrated that AT cells are hypersensitive to ionizing radiation5–7 and are defective at the Gl/S checkpoint after radiation damage8–10. Because cells lacking the protein tyrosine kinase c-Abl are also defective in radiation-induced Gl arrest11, we investigated the possibility that ATM might interact with c-Abl in response to radiation damage. Here we show that ATM binds c-Abl constitutively in control cells but not in AT cells. Our results demonstrate that the SH3 domain of c-Abl interacts with a DPAPNPPHFP motif (residues 1,373–1,382) of ATM. The results also reveal that radiation-induction of c-Abl tyrosine kinase activity is diminished in AT cells. These findings indicate that ATM is involved in the activation of c-Abl by DNA damage and this interaction may in part mediate radiation-induced Gl arrest.

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Author notes

  1. Kum Kum Khanna and Timothy Shafman: K.K.K, and TS. contributed equally to this work.

Authors and Affiliations

  1. Joint Center for Radiation Therapy and Division of Cancer Pharmacology, Dana-Farber Cancer Institutes, Boston, Massachusetts, 02115, USA
    Timothy Shafman, Surender Kharbanda & Donald Kufe
  2. The Queensland Institute of Medical Research, University of Queensland, Royal Brisbane Hospital, Herston, Brisbane, Queensland, 4029, Australia
    Kum Kum Khanna, Padmini Kedar, Kevin Spring, Sergei Kozlov, Karen Hobson, Magtouf Gatei, Ning Zhang, Dianne Watters, Mark Egerton & Martin F. Laving
  3. Department of Surgery, University of Queensland, Royal Brisbane Hospital, Herston, Brisbane, Queensland, 4029, Australia
    Martin F. Laving
  4. Fox Chase Cancer Center, Philadelphia, Pennsylvania, 19111, USA
    Tim Yen
  5. Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, RamatAviv, 69978, Israel
    Yosef Shiloh

Authors

  1. Timothy Shafman
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  2. Kum Kum Khanna
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  3. Padmini Kedar
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  4. Kevin Spring
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  5. Sergei Kozlov
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  6. Tim Yen
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  7. Karen Hobson
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  8. Magtouf Gatei
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  9. Ning Zhang
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  10. Dianne Watters
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  11. Mark Egerton
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  12. Yosef Shiloh
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  13. Surender Kharbanda
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  14. Donald Kufe
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  15. Martin F. Laving
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Shafman, T., Khanna, K., Kedar, P. et al. Interaction between ATM protein and c-Abl in response to DNA damage.Nature 387, 520–523 (1997). https://doi.org/10.1038/387520a0

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