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Role of ATM in oxidative stress-mediated c-Jun phosphorylation in response to ionizing radiation and CdCl2

S A Lee1, A Dritschilo, M Jung

  • 1Department of Radiation Medicine, Georgetown University Medical Center, Washington, D.C. 20007-2197, USA.

The Journal of Biological Chemistry
|March 30, 2001
PubMed

Insights

Ataxia telangiectasia (AT) cells show impaired c-Jun phosphorylation due to ATM gene mutation. ATM modulates oxidative stress signaling, impacting c-Jun phosphorylation and cellular redox homeostasis.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Genetics

Background:

  • Ataxia telangiectasia (AT) is a genetic disorder caused by mutations in the ATM gene.
  • The ATM gene plays a crucial role in DNA damage response and cellular signaling.
  • Impaired phosphorylation of the transcription factor c-Jun is observed in AT cells.

Purpose of the Study:

  • To investigate the role of ATM in c-Jun phosphorylation following ionizing radiation and oxidative stress.
  • To elucidate the mechanism by which ATM modulates oxidative stress-mediated signaling.

Main Methods:

  • Utilized fibroblasts from AT patients and control individuals.
  • Exposed cells to ionizing radiation and cadmium chloride (CdCl2), a pro-oxidant.
  • Assessed c-Jun phosphorylation at serine residues 63 and 73.
  • Measured heme oxygenase-1 (HO-1) induction as a marker of oxidative stress.
  • Expressed recombinant ATM in AT cells to observe its effects.

Main Results:

  • CdCl2 induced a biphasic increase in c-Jun phosphorylation in both AT and control cells, with a more pronounced second phase in AT cells.
  • Heme oxygenase-1 was significantly induced in AT fibroblasts.
  • Re-expression of ATM in AT cells attenuated the effects of CdCl2 on c-Jun phosphorylation and HO-1 induction.

Conclusions:

  • ATM plays a critical role in sensing ionizing radiation-induced oxidative stress.
  • ATM modulates intracellular redox homeostasis and oxidative stress-mediated signaling pathways.
  • ATM is essential for proper c-Jun phosphorylation in response to oxidative stress.

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