ATM blocks tunicamycin-induced endoplasmic reticulum stress

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Long He1, Sun Ok Kim, Osong Kwon

  • 1Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong, Daejeon 305-806, Republic of Korea.

FEBS Letters
|March 24, 2009
PubMed

Insights

The ataxia telangiectasia mutated (ATM) gene blocks endoplasmic reticulum stress (ER-stress). This finding is crucial for understanding cancer cell proliferation and developing targeted therapies.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Endoplasmic reticulum stress (ER-stress) is implicated in cancer cell proliferation.
  • The ataxia telangiectasia mutated (ATM) gene's role in ER-stress is not fully understood.

Purpose of the Study:

  • To investigate the role of the ATM gene in blocking ER-stress.
  • To elucidate the mechanisms by which ATM influences ER-stress signaling pathways.

Main Methods:

  • Utilized Atm-deficient AT5BIVA fibroblasts and wild-type ATM-transfected cells.
  • Induced ER-stress using tunicamycin and ionizing radiation (IR).
  • Assessed ER-stress markers including X-box protein-1 (XBP-1) splicing, GRP78 expression, and caspase activation via Western blotting and RT-PCR.

Main Results:

  • Tunicamycin or IR increased ER-stress markers in Atm-deficient cells.
  • Wild-type ATM expression significantly reduced tunicamycin-induced caspase activation.
  • ATM knockdown exacerbated ER-stress and increased sensitivity to tunicamycin.

Conclusions:

  • ATM acts as a critical suppressor of ER-stress.
  • ATM signaling is a key regulator of ER-stress pathways relevant to cancer proliferation.
  • Targeting ATM may offer therapeutic strategies for managing ER-stress in cancer.

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