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

ATM blocks tunicamycin-induced endoplasmic reticulum stress.

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

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.

PMID:
19302790
DOI:
10.1016/j.febslet.2009.02.002
[Indexed for MEDLINE]
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