ATM blocks tunicamycin-induced endoplasmic reticulum stress

FEBS Lett. 2009 Mar 4;583(5):903-8. doi: 10.1016/j.febslet.2009.02.002. Epub 2009 Feb 6.

Abstract

Endoplasmic reticulum stress (ER-stress) is associated with ataxia telangiectasia mutated (ATM) gene. We present here conclusive data showing that ATM blocks ER-stress induced by tunicamycin or ionizing radiation (IR). X-box protein-1 (XBP-1) splicing, GRP78 expression and caspase-12 activation were increased by tunicamycin or IR in Atm-deficient AT5BIVA fibroblasts. Activation of caspase-12 and caspase-3 by tunicamycin was significantly reduced in cells transfected with wild-type Atm (AT5BIVA/wtATM). Atm knockdown by siRNA, however, noticeably elevated ER-stress and chemosensitivity to tunicamycin. In summary, we present substantial data demonstrating that ATM blocks the ER stress signaling associated with cancer cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Ataxia Telangiectasia Mutated Proteins
  • Caspase 12 / metabolism
  • Caspase 3 / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Endoplasmic Reticulum / drug effects*
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum / radiation effects
  • Enzyme Activation / drug effects
  • Humans
  • Protein-Serine-Threonine Kinases / deficiency
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA, Small Interfering / genetics
  • Stress, Physiological / drug effects*
  • Stress, Physiological / radiation effects
  • Tumor Suppressor Proteins / deficiency
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Tunicamycin / pharmacology*

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • RNA, Small Interfering
  • Tumor Suppressor Proteins
  • Tunicamycin
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein-Serine-Threonine Kinases
  • Caspase 12
  • Caspase 3